Rheumatology

Patients with psoriasis treated with interleukin-12/23 inhibitors or IL-23 inhibitors were less likely to develop inflammatory arthritis, compared with those treated with tumor necrosis factor (TNF) inhibitors, according to findings from a large retrospective study.

While previous retrospective cohort studies have found biologic therapies for psoriasis can reduce the risk of developing psoriatic arthritis when compared with other treatments such as phototherapy and oral nonbiologic disease-modifying antirheumatic drugs, this analysis is the first to compare classes of biologics, Shikha Singla, MD, of the Medical College of Wisconsin, Milwaukee, and colleagues wrote in The Lancet Rheumatology.

In the analysis, researchers used the TriNetX database, which contains deidentified data from electronic medical health records from health care organizations across the United States. The study included adults diagnosed with psoriasis who were newly prescribed a biologic approved by the Food and Drug Administration for the treatment of psoriasis. Biologics were defined by drug class: anti-TNF, anti-IL-17, anti-IL-23, and anti–IL-12/23. Any patient with a diagnosis of psoriatic arthritis or other inflammatory arthritis prior to receiving a biologic prescription or within 2 weeks of receiving the prescription were excluded.

The researchers identified 15,501 eligible patients diagnosed with psoriasis during Jan. 1, 2014, to June 1, 2022, with an average follow-up time of 2.4 years. The researchers chose to start the study period in 2014 because the first non–anti-TNF drug for psoriatic arthritis was approved by the FDA in 2013 – the anti–IL-12/23 drug ustekinumab. During the study period, 976 patients developed inflammatory arthritis and were diagnosed on average 528 days after their biologic prescription.

In a multivariable analysis, the researchers found that patients prescribed IL-23 inhibitors (guselkumab [Tremfya], risankizumab [Skyrizi], tildrakizumab [Ilumya]) were nearly 60% less likely (adjusted hazard ratio, 0.41; 95% confidence interval, 0.17–0.95) to develop inflammatory arthritis than were patients taking TNF inhibitors (infliximab [Remicade], adalimumab [Humira], etanercept [Enbrel], golimumab [Simponi], certolizumab pegol [Cimzia]). The risk of developing arthritis was 42% lower (aHR, 0.58; 95% CI, 0.43-0.76) with the IL-12/23 inhibitor ustekinumab (Stelara), but there was no difference in outcomes among patients taking with IL-17 inhibitors (secukinumab [Cosentyx], ixekizumab [Taltz], or brodalumab [Siliq]), compared with TNF inhibitors. For the IL-12/23 inhibitor ustekinumab, all sensitivity analyses did not change this association. For IL-23 inhibitors, the results persisted when excluding patients who developed arthritis within 3 or 6 months after first biologic prescription and when using a higher diagnostic threshold for incident arthritis.

“There is a lot of interest in understanding if treatment of psoriasis will prevent onset of psoriatic arthritis,” said Joel M. Gelfand, MD, MSCE, director of the Psoriasis and Phototherapy Treatment Center at the University of Pennsylvania, Philadelphia, who was asked to comment on the results.

“To date, the literature is inconclusive with some studies suggesting biologics reduce risk of PsA, whereas others suggest biologic use is associated with an increased risk of PsA,” he said. “The current study is unique in that it compares biologic classes to one another and suggests that IL-12/23 and IL-23 biologics are associated with a reduced risk of PsA compared to psoriasis patients treated with TNF inhibitors and no difference was found between TNF inhibitors and IL-17 inhibitors.”

While the study posed an interesting research question, “I wouldn’t use these results to actually change treatment patterns,” Alexis R. Ogdie-Beatty, MD, an associate professor of medicine at the University of Pennsylvania, Philadelphia, said in an interview. She coauthored a commentary on the analysis. Dr. Gelfand also emphasized that this bias may have influenced the results and that these findings “should not impact clinical practice at this time.”

Although the analyses were strong, Dr. Ogdie-Beatty noted, there are inherent biases in this type of observational data that cannot be overcome. For example, if a patient comes into a dermatologist’s office with psoriasis and also has joint pain, the dermatologist may suspect that a patient could also have psoriatic arthritis and would be more likely to choose a drug that will work well for both of these conditions.

“The drugs that are known to work best for psoriatic arthritis are the TNF inhibitors and the IL-17 inhibitors,” she said. So, while the analysis found these medications were associated with higher incidence of PsA, the dermatologist was possibly treating presumptive arthritis and the patient had yet to be referred to a rheumatologist to confirm the diagnosis.

The researchers noted that they attempted to mitigate these issues by requiring that patients have at least 1 year of follow-up before receiving biologic prescription “to capture only the patients with no previous codes for any type of arthritis,” as well as conducting six sensitivity analyses.

The authors, and Dr. Ogdie-Beatty and Dr. Gelfand agreed that more research is necessary to confirm these findings. A large randomized trial may be “prohibitively expensive,” the authors noted, but pooled analyses from previous clinical trials may help with this issue. “We identified 14 published randomized trials that did head-to-head comparisons of different biologic classes with regard to effect on psoriasis, and these trials collectively contained data on more than 13,000 patients. Pooled analyses of these data could confirm the findings of the present study and would be adequately powered.”

But that approach also has limitations, as psoriatic arthritis was not assessed an outcome in these studies, Dr. Ogdie-Beatty noted. Randomizing patients who are already at a higher risk of developing PsA to different biologics could be one approach to address these questions without needing such a large patient population.

The study was conducted without outside funding or industry involvement. Dr. Singla reported no relevant financial relationships with industry, but several coauthors reported financial relationships with pharmaceutical companies that market biologics for psoriasis and psoriatic arthritis. Dr. Ogdie-Beatty reported financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, CorEvitas, Gilead, Happify Health, Janssen, Lilly, Novartis, Pfizer, and UCB. Dr. Gelfand reported financial relationships with Abbvie, Amgen, BMS, Boehringer Ingelheim, FIDE, Lilly, Leo, Janssen Biologics, Novartis, Pfizer, and UCB. Dr. Gelfand is a deputy editor for the Journal of Investigative Dermatology.

This article was updated 3/15/23.

Patients with psoriasis treated with interleukin-12/23 inhibitors or IL-23 inhibitors were less likely to develop inflammatory arthritis, compared with those treated with tumor necrosis factor (TNF) inhibitors, according to findings from a large retrospective study.

While previous retrospective cohort studies have found biologic therapies for psoriasis can reduce the risk of developing psoriatic arthritis when compared with other treatments such as phototherapy and oral nonbiologic disease-modifying antirheumatic drugs, this analysis is the first to compare classes of biologics, Shikha Singla, MD, of the Medical College of Wisconsin, Milwaukee, and colleagues wrote in The Lancet Rheumatology.

In the analysis, researchers used the TriNetX database, which contains deidentified data from electronic medical health records from health care organizations across the United States. The study included adults diagnosed with psoriasis who were newly prescribed a biologic approved by the Food and Drug Administration for the treatment of psoriasis. Biologics were defined by drug class: anti-TNF, anti-IL-17, anti-IL-23, and anti–IL-12/23. Any patient with a diagnosis of psoriatic arthritis or other inflammatory arthritis prior to receiving a biologic prescription or within 2 weeks of receiving the prescription were excluded.

The researchers identified 15,501 eligible patients diagnosed with psoriasis during Jan. 1, 2014, to June 1, 2022, with an average follow-up time of 2.4 years. The researchers chose to start the study period in 2014 because the first non–anti-TNF drug for psoriatic arthritis was approved by the FDA in 2013 – the anti–IL-12/23 drug ustekinumab. During the study period, 976 patients developed inflammatory arthritis and were diagnosed on average 528 days after their biologic prescription.

In a multivariable analysis, the researchers found that patients prescribed IL-23 inhibitors (guselkumab [Tremfya], risankizumab [Skyrizi], tildrakizumab [Ilumya]) were nearly 60% less likely (adjusted hazard ratio, 0.41; 95% confidence interval, 0.17–0.95) to develop inflammatory arthritis than were patients taking TNF inhibitors (infliximab [Remicade], adalimumab [Humira], etanercept [Enbrel], golimumab [Simponi], certolizumab pegol [Cimzia]). The risk of developing arthritis was 42% lower (aHR, 0.58; 95% CI, 0.43-0.76) with the IL-12/23 inhibitor ustekinumab (Stelara), but there was no difference in outcomes among patients taking with IL-17 inhibitors (secukinumab [Cosentyx], ixekizumab [Taltz], or brodalumab [Siliq]), compared with TNF inhibitors. For the IL-12/23 inhibitor ustekinumab, all sensitivity analyses did not change this association. For IL-23 inhibitors, the results persisted when excluding patients who developed arthritis within 3 or 6 months after first biologic prescription and when using a higher diagnostic threshold for incident arthritis.

“There is a lot of interest in understanding if treatment of psoriasis will prevent onset of psoriatic arthritis,” said Joel M. Gelfand, MD, MSCE, director of the Psoriasis and Phototherapy Treatment Center at the University of Pennsylvania, Philadelphia, who was asked to comment on the results.

“To date, the literature is inconclusive with some studies suggesting biologics reduce risk of PsA, whereas others suggest biologic use is associated with an increased risk of PsA,” he said. “The current study is unique in that it compares biologic classes to one another and suggests that IL-12/23 and IL-23 biologics are associated with a reduced risk of PsA compared to psoriasis patients treated with TNF inhibitors and no difference was found between TNF inhibitors and IL-17 inhibitors.”

While the study posed an interesting research question, “I wouldn’t use these results to actually change treatment patterns,” Alexis R. Ogdie-Beatty, MD, an associate professor of medicine at the University of Pennsylvania, Philadelphia, said in an interview. She coauthored a commentary on the analysis. Dr. Gelfand also emphasized that this bias may have influenced the results and that these findings “should not impact clinical practice at this time.”

Although the analyses were strong, Dr. Ogdie-Beatty noted, there are inherent biases in this type of observational data that cannot be overcome. For example, if a patient comes into a dermatologist’s office with psoriasis and also has joint pain, the dermatologist may suspect that a patient could also have psoriatic arthritis and would be more likely to choose a drug that will work well for both of these conditions.

“The drugs that are known to work best for psoriatic arthritis are the TNF inhibitors and the IL-17 inhibitors,” she said. So, while the analysis found these medications were associated with higher incidence of PsA, the dermatologist was possibly treating presumptive arthritis and the patient had yet to be referred to a rheumatologist to confirm the diagnosis.

The researchers noted that they attempted to mitigate these issues by requiring that patients have at least 1 year of follow-up before receiving biologic prescription “to capture only the patients with no previous codes for any type of arthritis,” as well as conducting six sensitivity analyses.

The authors, and Dr. Ogdie-Beatty and Dr. Gelfand agreed that more research is necessary to confirm these findings. A large randomized trial may be “prohibitively expensive,” the authors noted, but pooled analyses from previous clinical trials may help with this issue. “We identified 14 published randomized trials that did head-to-head comparisons of different biologic classes with regard to effect on psoriasis, and these trials collectively contained data on more than 13,000 patients. Pooled analyses of these data could confirm the findings of the present study and would be adequately powered.”

But that approach also has limitations, as psoriatic arthritis was not assessed an outcome in these studies, Dr. Ogdie-Beatty noted. Randomizing patients who are already at a higher risk of developing PsA to different biologics could be one approach to address these questions without needing such a large patient population.

The study was conducted without outside funding or industry involvement. Dr. Singla reported no relevant financial relationships with industry, but several coauthors reported financial relationships with pharmaceutical companies that market biologics for psoriasis and psoriatic arthritis. Dr. Ogdie-Beatty reported financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, CorEvitas, Gilead, Happify Health, Janssen, Lilly, Novartis, Pfizer, and UCB. Dr. Gelfand reported financial relationships with Abbvie, Amgen, BMS, Boehringer Ingelheim, FIDE, Lilly, Leo, Janssen Biologics, Novartis, Pfizer, and UCB. Dr. Gelfand is a deputy editor for the Journal of Investigative Dermatology.

This article was updated 3/15/23.

Patients with psoriasis treated with interleukin-12/23 inhibitors or IL-23 inhibitors were less likely to develop inflammatory arthritis, compared with those treated with tumor necrosis factor (TNF) inhibitors, according to findings from a large retrospective study.

While previous retrospective cohort studies have found biologic therapies for psoriasis can reduce the risk of developing psoriatic arthritis when compared with other treatments such as phototherapy and oral nonbiologic disease-modifying antirheumatic drugs, this analysis is the first to compare classes of biologics, Shikha Singla, MD, of the Medical College of Wisconsin, Milwaukee, and colleagues wrote in The Lancet Rheumatology.

In the analysis, researchers used the TriNetX database, which contains deidentified data from electronic medical health records from health care organizations across the United States. The study included adults diagnosed with psoriasis who were newly prescribed a biologic approved by the Food and Drug Administration for the treatment of psoriasis. Biologics were defined by drug class: anti-TNF, anti-IL-17, anti-IL-23, and anti–IL-12/23. Any patient with a diagnosis of psoriatic arthritis or other inflammatory arthritis prior to receiving a biologic prescription or within 2 weeks of receiving the prescription were excluded.

The researchers identified 15,501 eligible patients diagnosed with psoriasis during Jan. 1, 2014, to June 1, 2022, with an average follow-up time of 2.4 years. The researchers chose to start the study period in 2014 because the first non–anti-TNF drug for psoriatic arthritis was approved by the FDA in 2013 – the anti–IL-12/23 drug ustekinumab. During the study period, 976 patients developed inflammatory arthritis and were diagnosed on average 528 days after their biologic prescription.

In a multivariable analysis, the researchers found that patients prescribed IL-23 inhibitors (guselkumab [Tremfya], risankizumab [Skyrizi], tildrakizumab [Ilumya]) were nearly 60% less likely (adjusted hazard ratio, 0.41; 95% confidence interval, 0.17–0.95) to develop inflammatory arthritis than were patients taking TNF inhibitors (infliximab [Remicade], adalimumab [Humira], etanercept [Enbrel], golimumab [Simponi], certolizumab pegol [Cimzia]). The risk of developing arthritis was 42% lower (aHR, 0.58; 95% CI, 0.43-0.76) with the IL-12/23 inhibitor ustekinumab (Stelara), but there was no difference in outcomes among patients taking with IL-17 inhibitors (secukinumab [Cosentyx], ixekizumab [Taltz], or brodalumab [Siliq]), compared with TNF inhibitors. For the IL-12/23 inhibitor ustekinumab, all sensitivity analyses did not change this association. For IL-23 inhibitors, the results persisted when excluding patients who developed arthritis within 3 or 6 months after first biologic prescription and when using a higher diagnostic threshold for incident arthritis.

“There is a lot of interest in understanding if treatment of psoriasis will prevent onset of psoriatic arthritis,” said Joel M. Gelfand, MD, MSCE, director of the Psoriasis and Phototherapy Treatment Center at the University of Pennsylvania, Philadelphia, who was asked to comment on the results.

“To date, the literature is inconclusive with some studies suggesting biologics reduce risk of PsA, whereas others suggest biologic use is associated with an increased risk of PsA,” he said. “The current study is unique in that it compares biologic classes to one another and suggests that IL-12/23 and IL-23 biologics are associated with a reduced risk of PsA compared to psoriasis patients treated with TNF inhibitors and no difference was found between TNF inhibitors and IL-17 inhibitors.”

While the study posed an interesting research question, “I wouldn’t use these results to actually change treatment patterns,” Alexis R. Ogdie-Beatty, MD, an associate professor of medicine at the University of Pennsylvania, Philadelphia, said in an interview. She coauthored a commentary on the analysis. Dr. Gelfand also emphasized that this bias may have influenced the results and that these findings “should not impact clinical practice at this time.”

Although the analyses were strong, Dr. Ogdie-Beatty noted, there are inherent biases in this type of observational data that cannot be overcome. For example, if a patient comes into a dermatologist’s office with psoriasis and also has joint pain, the dermatologist may suspect that a patient could also have psoriatic arthritis and would be more likely to choose a drug that will work well for both of these conditions.

“The drugs that are known to work best for psoriatic arthritis are the TNF inhibitors and the IL-17 inhibitors,” she said. So, while the analysis found these medications were associated with higher incidence of PsA, the dermatologist was possibly treating presumptive arthritis and the patient had yet to be referred to a rheumatologist to confirm the diagnosis.

The researchers noted that they attempted to mitigate these issues by requiring that patients have at least 1 year of follow-up before receiving biologic prescription “to capture only the patients with no previous codes for any type of arthritis,” as well as conducting six sensitivity analyses.

The authors, and Dr. Ogdie-Beatty and Dr. Gelfand agreed that more research is necessary to confirm these findings. A large randomized trial may be “prohibitively expensive,” the authors noted, but pooled analyses from previous clinical trials may help with this issue. “We identified 14 published randomized trials that did head-to-head comparisons of different biologic classes with regard to effect on psoriasis, and these trials collectively contained data on more than 13,000 patients. Pooled analyses of these data could confirm the findings of the present study and would be adequately powered.”

But that approach also has limitations, as psoriatic arthritis was not assessed an outcome in these studies, Dr. Ogdie-Beatty noted. Randomizing patients who are already at a higher risk of developing PsA to different biologics could be one approach to address these questions without needing such a large patient population.

The study was conducted without outside funding or industry involvement. Dr. Singla reported no relevant financial relationships with industry, but several coauthors reported financial relationships with pharmaceutical companies that market biologics for psoriasis and psoriatic arthritis. Dr. Ogdie-Beatty reported financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, CorEvitas, Gilead, Happify Health, Janssen, Lilly, Novartis, Pfizer, and UCB. Dr. Gelfand reported financial relationships with Abbvie, Amgen, BMS, Boehringer Ingelheim, FIDE, Lilly, Leo, Janssen Biologics, Novartis, Pfizer, and UCB. Dr. Gelfand is a deputy editor for the Journal of Investigative Dermatology.

This article was updated 3/15/23.

Although patients with lupus nephritis recently gained two new add-on treatment options in voclosporin (Lupkynis) and belimumab (Benlysta), there have been little data published with real-world experience in using these drugs.

Voclosporin, a calcineurin inhibitor, was approved by the Food and Drug Administration in January 2021 to treat lupus nephritis in combination with immunosuppressive medication. Belimumab, a human monoclonal antibody and B-lymphocyte stimulator, was approved in December 2020 in the United States as an add-on treatment for lupus nephritis in adults and later in July 2022 for children who are already receiving standard therapy.

How the two drugs are prescribed for patients with lupus nephritis so far appears to be influenced by presence of extrarenal manifestations of lupus, proteinuria level, clinicians’ prior experience with belimumab, costs of the drugs, and patient preference, experts said.

Voclosporin’s approval was based on data from the phase 3 AURORA 1 trial and phase 2 AURA-LV trial. AURORA 1 evaluated 357 patients with systemic lupus erythematosus (SLE) and lupus nephritis who were randomized to receive voclosporin or placebo with mycophenolate mofetil and tapered low-dose oral steroids. In the voclosporin group, the results showed a significantly higher complete renal response at 52 weeks, compared with the placebo group, while having a similar adverse event profile. The AURA-LV trial, evaluating efficacy and safety of 179 patients with lupus nephritis, showed adding low-dose voclosporin to induction therapy improved renal response, compared with placebo. AURORA 2, a continuation of the AURORA trial, showed patients with lupus nephritis receiving voclosporin have a stable estimated glomerular filtration rate and reductions in proteinuria up to 3 years of follow-up.

Results from the phase 3 BLISS-LN trial of 448 patients with confirmed lupus nephritis were the basis for belimumab’s approval and showed a significantly higher proportion of patients who received belimumab had a primary efficacy renal response, complete renal response, and significantly lower risk of a renal-related adverse event or death, compared with the placebo group.
 

Lack of real-world data

The lack of real-world data on either of these treatments can be attributed to lupus nephritis being a rare disease, and the approvals happening fairly recently, experts said.

“This is really due to the recency of the approvals for both of these medications for lupus nephritis,” Amit Saxena, MD, a rheumatologist and assistant professor of medicine in the division of rheumatology at NYU Langone Health in New York, said in an interview.

“It’s too soon for any appreciable data to be collected.”

Ashira D. Blazer, MD, MSCI, a rheumatologist at Hospital for Special Surgery and assistant professor of medicine at Weill Cornell Medical College, both in New York, said that rheumatologists “are a little bit hesitant” to use newer agents rather than existing therapies, and have existing guidance from the American College of Rheumatology (ACR) on treating the condition.

“I think when someone has something like lupus nephritis that’s so serious, rheumatologists pull for the tried-and-true drugs that we know will affect the inflammation quickly and get that patient to remission,” she said.

Donald E. Thomas Jr., MD, of Arthritis and Pain Associates of P.G. County in Greenbelt, Md., said he was surprised there was a lack of case studies on voclosporin or belimumab for lupus nephritis, but pointed to the time and cost of publishing a case report and the rheumatologist shortage as potential reasons.

Sharon Worcester/MDedge News

Prescribing experience

Despite the lack of published data on real-world use, the drugs are being prescribed, Dr. Thomas said.

“I have quite a few patients on these drugs,” he said, citing one patient with severe membranoproliferative lupus nephritis not in remission who is receiving a combination of voclosporin, belimumab, and hydroxychloroquine.

“I have had absolutely no problems getting either drug. The indications for the medicines are crystal clear,” he said.

Irene Blanco, MD, MS, professor in the department of medicine-rheumatology at Northwestern University, Chicago, said that in her experience, both voclosporin and belimumab have been easy to get for patients.

However, she noted she was seeing mostly patients with government-based insurance in the Bronx, N.Y., prior to moving to Northwestern in September 2022. Belimumab had been available from the New York State Medicaid program for indications other than lupus nephritis for some time, and the program was quick to add voclosporin once it became available. “It wasn’t hard to get at all,” she said.

Dr. Saxena noted the respective pharmaceutical companies have provided help in prescribing voclosporin and belimumab through offering patient assistance programs and navigating insurers’ prior authorization hurdles. As belimumab has been available for many years, its availability hasn’t changed, he noted. “Voclosporin has seen more formulary restrictions, but in my experience, I have been able to get the drug utilizing authorization procedures,” he said.

One issue Dr. Blazer said that she encounters is cost. According to prices obtained from drugs.com in March 2023, belimumab has an estimated annual price of $58.389.96 per patient, and voclosporin has an estimated annual price of $86,506.20 per patient.

“I tend to treat patients who can have some socioeconomic challenges, and so I think very long and hard before prescribing either of them,” she explained. “[C]ertainly in the case of voclosporin, when there are older, cheaper calcineurin inhibitors and I think I need one, I’m more likely to reach for one of the others.”

While GSK offers a patient assistance program for belimumab, which Dr. Blazer said she has used, physicians may not be aware of the program or have the resources in their offices to provide social work support for their patients.

“I have had patients who started it and ... continued to have a flare and needed to go on disability or leave their jobs, and they were just too concerned with the ongoing cost burden, and so I ended up taking them off the medication for that reason at their request,” she said.

The fact that Black patients have lupus nephritis more often than White patients do, as well as greater socioeconomic barriers, points to access to care and cost as major factors in why new drugs are not being used, Dr. Blazer said. “I think that understanding how we can improve access is going to be extremely important in getting more real-world data and getting more patients treated,” she said.

Treatment preference

A chart audit recently released by market research firm Spherix Global Insights highlighted a potential treatment preference for lupus nephritis. Use of voclosporin increased among rheumatologists and nephrologists, but patients with lupus nephritis under the care of rheumatologists were more likely to be treated with belimumab than voclosporin.

Dr. Saxena said he has experience with both and doesn’t have a preference, instead using factors other than experience when deciding the best treatment for patients. “For example, if there are nonrenal manifestations such as arthritis or rashes, I may lean towards belimumab, but if a more rapid reduction in proteinuria is important, I may lean towards voclosporin,” he said.

Dr. Thomas weighs the pros and cons of voclosporin and belimumab with the patient. “With many lupus nephritis scenarios, either drug may be a good choice and it comes down to patient preference. The main scenario where I would choose [voclosporin] over [belimumab] is in patients with [proteinuria of] 3 g protein/day or more,” he said, while belimumab would be the choice for a patient with “nonrenal manifestations of SLE in addition to their nephritis.”

For other rheumatologists, comfort level with belimumab may play a role. “We always had [belimumab] and we were always using [belimumab], and so it would make sense that like we would go for a med, again, that we’re really familiar with and we use,” Dr. Blanco said.

Dr. Blanco has prescribed belimumab, but had been using tacrolimus until recently. “I’ve been using tacrolimus since 2016. I’m probably going to lean on the [tacrolimus] rather than going to [belimumab], which works, but maybe it’s not the end-all, be-all in terms of lupus,” she said.

Although she hasn’t yet prescribed voclosporin, Dr. Blazer said she had “much more experience with belimumab.

“I’ve prescribed other calcineurin inhibitors in the past, and usually for a patient who’s very proteinuric and as an adjunct to that standard of care to try to bring down the proteinuria,” she said.

With belimumab, she would consider adding it to a patient with severe disease who has failed treatment with mycophenolate mofetil or cyclophosphamide and has a recurrent lupus nephritis flare. “It’s something I can use as an adjunct, and I think that I can get some extra benefit from it, and it also tends to be well tolerated,” Dr. Blazer said.

How patients are responding

Dr. Thomas’ patients have been responding well on voclosporin and belimumab. “I was an early adopter of [belimumab] and had patients with lupus nephritis do great on it, way before the FDA approval,” he said.

For voclosporin, Dr. Thomas highlighted the “incredibly rapid” proteinuria response. “I had a patient have marked reduction in proteinuria in just 2 weeks. Proteinuria reduction is the number one predictor of long-term better outcomes,” he said.

Many patients receiving mycophenolate and cyclophosphamide do not go into complete remission, while the clinical trials for voclosporin and belimumab had significantly higher rates of complete response and faster response rates, compared with older therapies. “That is what we need,” he said.

“These drugs are game changers in the treatment of lupus nephritis. In my mind, belimumab and voclosporin should be considered the standard of medical care treating lupus nephritis patients,” he added.

Dr. Blanco said her patients appear to like and are tolerating voclosporin and belimumab well, but because there are no pregnancy data on voclosporin, she may choose belimumab or tacrolimus for patients of reproductive age who are considering starting a family.

Patients with extrarenal symptoms tend to do particularly well with belimumab, such as those with arthritis and skin rash, Dr. Blazer said. “In my experience, as an adjunct with those standard of care medications, I have been able to maintain remission in my patients,” she said.

Dr. Saxena said both medications are “important options” for lupus nephritis in patients who don’t respond to standard therapy. “As more doctors utilize each medication and additional data is published, I’d expect an increase uptake in both medications in the future,” he said.

Dr. Blazer reported being a contributor to GSK’s SLE Educators’ Network and has been a consultant for Aurinia. Dr. Saxena reported being a consultant for GSK and Aurinia. Dr. Thomas reported being on the speakers bureau for GSK and Aurinia. Dr. Blanco reported having no relevant financial relationships with pharmaceutical companies.

Although patients with lupus nephritis recently gained two new add-on treatment options in voclosporin (Lupkynis) and belimumab (Benlysta), there have been little data published with real-world experience in using these drugs.

Voclosporin, a calcineurin inhibitor, was approved by the Food and Drug Administration in January 2021 to treat lupus nephritis in combination with immunosuppressive medication. Belimumab, a human monoclonal antibody and B-lymphocyte stimulator, was approved in December 2020 in the United States as an add-on treatment for lupus nephritis in adults and later in July 2022 for children who are already receiving standard therapy.

How the two drugs are prescribed for patients with lupus nephritis so far appears to be influenced by presence of extrarenal manifestations of lupus, proteinuria level, clinicians’ prior experience with belimumab, costs of the drugs, and patient preference, experts said.

Voclosporin’s approval was based on data from the phase 3 AURORA 1 trial and phase 2 AURA-LV trial. AURORA 1 evaluated 357 patients with systemic lupus erythematosus (SLE) and lupus nephritis who were randomized to receive voclosporin or placebo with mycophenolate mofetil and tapered low-dose oral steroids. In the voclosporin group, the results showed a significantly higher complete renal response at 52 weeks, compared with the placebo group, while having a similar adverse event profile. The AURA-LV trial, evaluating efficacy and safety of 179 patients with lupus nephritis, showed adding low-dose voclosporin to induction therapy improved renal response, compared with placebo. AURORA 2, a continuation of the AURORA trial, showed patients with lupus nephritis receiving voclosporin have a stable estimated glomerular filtration rate and reductions in proteinuria up to 3 years of follow-up.

Results from the phase 3 BLISS-LN trial of 448 patients with confirmed lupus nephritis were the basis for belimumab’s approval and showed a significantly higher proportion of patients who received belimumab had a primary efficacy renal response, complete renal response, and significantly lower risk of a renal-related adverse event or death, compared with the placebo group.
 

Lack of real-world data

The lack of real-world data on either of these treatments can be attributed to lupus nephritis being a rare disease, and the approvals happening fairly recently, experts said.

“This is really due to the recency of the approvals for both of these medications for lupus nephritis,” Amit Saxena, MD, a rheumatologist and assistant professor of medicine in the division of rheumatology at NYU Langone Health in New York, said in an interview.

“It’s too soon for any appreciable data to be collected.”

Ashira D. Blazer, MD, MSCI, a rheumatologist at Hospital for Special Surgery and assistant professor of medicine at Weill Cornell Medical College, both in New York, said that rheumatologists “are a little bit hesitant” to use newer agents rather than existing therapies, and have existing guidance from the American College of Rheumatology (ACR) on treating the condition.

“I think when someone has something like lupus nephritis that’s so serious, rheumatologists pull for the tried-and-true drugs that we know will affect the inflammation quickly and get that patient to remission,” she said.

Donald E. Thomas Jr., MD, of Arthritis and Pain Associates of P.G. County in Greenbelt, Md., said he was surprised there was a lack of case studies on voclosporin or belimumab for lupus nephritis, but pointed to the time and cost of publishing a case report and the rheumatologist shortage as potential reasons.

Sharon Worcester/MDedge News

Prescribing experience

Despite the lack of published data on real-world use, the drugs are being prescribed, Dr. Thomas said.

“I have quite a few patients on these drugs,” he said, citing one patient with severe membranoproliferative lupus nephritis not in remission who is receiving a combination of voclosporin, belimumab, and hydroxychloroquine.

“I have had absolutely no problems getting either drug. The indications for the medicines are crystal clear,” he said.

Irene Blanco, MD, MS, professor in the department of medicine-rheumatology at Northwestern University, Chicago, said that in her experience, both voclosporin and belimumab have been easy to get for patients.

However, she noted she was seeing mostly patients with government-based insurance in the Bronx, N.Y., prior to moving to Northwestern in September 2022. Belimumab had been available from the New York State Medicaid program for indications other than lupus nephritis for some time, and the program was quick to add voclosporin once it became available. “It wasn’t hard to get at all,” she said.

Dr. Saxena noted the respective pharmaceutical companies have provided help in prescribing voclosporin and belimumab through offering patient assistance programs and navigating insurers’ prior authorization hurdles. As belimumab has been available for many years, its availability hasn’t changed, he noted. “Voclosporin has seen more formulary restrictions, but in my experience, I have been able to get the drug utilizing authorization procedures,” he said.

One issue Dr. Blazer said that she encounters is cost. According to prices obtained from drugs.com in March 2023, belimumab has an estimated annual price of $58.389.96 per patient, and voclosporin has an estimated annual price of $86,506.20 per patient.

“I tend to treat patients who can have some socioeconomic challenges, and so I think very long and hard before prescribing either of them,” she explained. “[C]ertainly in the case of voclosporin, when there are older, cheaper calcineurin inhibitors and I think I need one, I’m more likely to reach for one of the others.”

While GSK offers a patient assistance program for belimumab, which Dr. Blazer said she has used, physicians may not be aware of the program or have the resources in their offices to provide social work support for their patients.

“I have had patients who started it and ... continued to have a flare and needed to go on disability or leave their jobs, and they were just too concerned with the ongoing cost burden, and so I ended up taking them off the medication for that reason at their request,” she said.

The fact that Black patients have lupus nephritis more often than White patients do, as well as greater socioeconomic barriers, points to access to care and cost as major factors in why new drugs are not being used, Dr. Blazer said. “I think that understanding how we can improve access is going to be extremely important in getting more real-world data and getting more patients treated,” she said.

Treatment preference

A chart audit recently released by market research firm Spherix Global Insights highlighted a potential treatment preference for lupus nephritis. Use of voclosporin increased among rheumatologists and nephrologists, but patients with lupus nephritis under the care of rheumatologists were more likely to be treated with belimumab than voclosporin.

Dr. Saxena said he has experience with both and doesn’t have a preference, instead using factors other than experience when deciding the best treatment for patients. “For example, if there are nonrenal manifestations such as arthritis or rashes, I may lean towards belimumab, but if a more rapid reduction in proteinuria is important, I may lean towards voclosporin,” he said.

Dr. Thomas weighs the pros and cons of voclosporin and belimumab with the patient. “With many lupus nephritis scenarios, either drug may be a good choice and it comes down to patient preference. The main scenario where I would choose [voclosporin] over [belimumab] is in patients with [proteinuria of] 3 g protein/day or more,” he said, while belimumab would be the choice for a patient with “nonrenal manifestations of SLE in addition to their nephritis.”

For other rheumatologists, comfort level with belimumab may play a role. “We always had [belimumab] and we were always using [belimumab], and so it would make sense that like we would go for a med, again, that we’re really familiar with and we use,” Dr. Blanco said.

Dr. Blanco has prescribed belimumab, but had been using tacrolimus until recently. “I’ve been using tacrolimus since 2016. I’m probably going to lean on the [tacrolimus] rather than going to [belimumab], which works, but maybe it’s not the end-all, be-all in terms of lupus,” she said.

Although she hasn’t yet prescribed voclosporin, Dr. Blazer said she had “much more experience with belimumab.

“I’ve prescribed other calcineurin inhibitors in the past, and usually for a patient who’s very proteinuric and as an adjunct to that standard of care to try to bring down the proteinuria,” she said.

With belimumab, she would consider adding it to a patient with severe disease who has failed treatment with mycophenolate mofetil or cyclophosphamide and has a recurrent lupus nephritis flare. “It’s something I can use as an adjunct, and I think that I can get some extra benefit from it, and it also tends to be well tolerated,” Dr. Blazer said.

How patients are responding

Dr. Thomas’ patients have been responding well on voclosporin and belimumab. “I was an early adopter of [belimumab] and had patients with lupus nephritis do great on it, way before the FDA approval,” he said.

For voclosporin, Dr. Thomas highlighted the “incredibly rapid” proteinuria response. “I had a patient have marked reduction in proteinuria in just 2 weeks. Proteinuria reduction is the number one predictor of long-term better outcomes,” he said.

Many patients receiving mycophenolate and cyclophosphamide do not go into complete remission, while the clinical trials for voclosporin and belimumab had significantly higher rates of complete response and faster response rates, compared with older therapies. “That is what we need,” he said.

“These drugs are game changers in the treatment of lupus nephritis. In my mind, belimumab and voclosporin should be considered the standard of medical care treating lupus nephritis patients,” he added.

Dr. Blanco said her patients appear to like and are tolerating voclosporin and belimumab well, but because there are no pregnancy data on voclosporin, she may choose belimumab or tacrolimus for patients of reproductive age who are considering starting a family.

Patients with extrarenal symptoms tend to do particularly well with belimumab, such as those with arthritis and skin rash, Dr. Blazer said. “In my experience, as an adjunct with those standard of care medications, I have been able to maintain remission in my patients,” she said.

Dr. Saxena said both medications are “important options” for lupus nephritis in patients who don’t respond to standard therapy. “As more doctors utilize each medication and additional data is published, I’d expect an increase uptake in both medications in the future,” he said.

Dr. Blazer reported being a contributor to GSK’s SLE Educators’ Network and has been a consultant for Aurinia. Dr. Saxena reported being a consultant for GSK and Aurinia. Dr. Thomas reported being on the speakers bureau for GSK and Aurinia. Dr. Blanco reported having no relevant financial relationships with pharmaceutical companies.

Although patients with lupus nephritis recently gained two new add-on treatment options in voclosporin (Lupkynis) and belimumab (Benlysta), there have been little data published with real-world experience in using these drugs.

Voclosporin, a calcineurin inhibitor, was approved by the Food and Drug Administration in January 2021 to treat lupus nephritis in combination with immunosuppressive medication. Belimumab, a human monoclonal antibody and B-lymphocyte stimulator, was approved in December 2020 in the United States as an add-on treatment for lupus nephritis in adults and later in July 2022 for children who are already receiving standard therapy.

How the two drugs are prescribed for patients with lupus nephritis so far appears to be influenced by presence of extrarenal manifestations of lupus, proteinuria level, clinicians’ prior experience with belimumab, costs of the drugs, and patient preference, experts said.

Voclosporin’s approval was based on data from the phase 3 AURORA 1 trial and phase 2 AURA-LV trial. AURORA 1 evaluated 357 patients with systemic lupus erythematosus (SLE) and lupus nephritis who were randomized to receive voclosporin or placebo with mycophenolate mofetil and tapered low-dose oral steroids. In the voclosporin group, the results showed a significantly higher complete renal response at 52 weeks, compared with the placebo group, while having a similar adverse event profile. The AURA-LV trial, evaluating efficacy and safety of 179 patients with lupus nephritis, showed adding low-dose voclosporin to induction therapy improved renal response, compared with placebo. AURORA 2, a continuation of the AURORA trial, showed patients with lupus nephritis receiving voclosporin have a stable estimated glomerular filtration rate and reductions in proteinuria up to 3 years of follow-up.

Results from the phase 3 BLISS-LN trial of 448 patients with confirmed lupus nephritis were the basis for belimumab’s approval and showed a significantly higher proportion of patients who received belimumab had a primary efficacy renal response, complete renal response, and significantly lower risk of a renal-related adverse event or death, compared with the placebo group.
 

Lack of real-world data

The lack of real-world data on either of these treatments can be attributed to lupus nephritis being a rare disease, and the approvals happening fairly recently, experts said.

“This is really due to the recency of the approvals for both of these medications for lupus nephritis,” Amit Saxena, MD, a rheumatologist and assistant professor of medicine in the division of rheumatology at NYU Langone Health in New York, said in an interview.

“It’s too soon for any appreciable data to be collected.”

Ashira D. Blazer, MD, MSCI, a rheumatologist at Hospital for Special Surgery and assistant professor of medicine at Weill Cornell Medical College, both in New York, said that rheumatologists “are a little bit hesitant” to use newer agents rather than existing therapies, and have existing guidance from the American College of Rheumatology (ACR) on treating the condition.

“I think when someone has something like lupus nephritis that’s so serious, rheumatologists pull for the tried-and-true drugs that we know will affect the inflammation quickly and get that patient to remission,” she said.

Donald E. Thomas Jr., MD, of Arthritis and Pain Associates of P.G. County in Greenbelt, Md., said he was surprised there was a lack of case studies on voclosporin or belimumab for lupus nephritis, but pointed to the time and cost of publishing a case report and the rheumatologist shortage as potential reasons.

Sharon Worcester/MDedge News

Prescribing experience

Despite the lack of published data on real-world use, the drugs are being prescribed, Dr. Thomas said.

“I have quite a few patients on these drugs,” he said, citing one patient with severe membranoproliferative lupus nephritis not in remission who is receiving a combination of voclosporin, belimumab, and hydroxychloroquine.

“I have had absolutely no problems getting either drug. The indications for the medicines are crystal clear,” he said.

Irene Blanco, MD, MS, professor in the department of medicine-rheumatology at Northwestern University, Chicago, said that in her experience, both voclosporin and belimumab have been easy to get for patients.

However, she noted she was seeing mostly patients with government-based insurance in the Bronx, N.Y., prior to moving to Northwestern in September 2022. Belimumab had been available from the New York State Medicaid program for indications other than lupus nephritis for some time, and the program was quick to add voclosporin once it became available. “It wasn’t hard to get at all,” she said.

Dr. Saxena noted the respective pharmaceutical companies have provided help in prescribing voclosporin and belimumab through offering patient assistance programs and navigating insurers’ prior authorization hurdles. As belimumab has been available for many years, its availability hasn’t changed, he noted. “Voclosporin has seen more formulary restrictions, but in my experience, I have been able to get the drug utilizing authorization procedures,” he said.

One issue Dr. Blazer said that she encounters is cost. According to prices obtained from drugs.com in March 2023, belimumab has an estimated annual price of $58.389.96 per patient, and voclosporin has an estimated annual price of $86,506.20 per patient.

“I tend to treat patients who can have some socioeconomic challenges, and so I think very long and hard before prescribing either of them,” she explained. “[C]ertainly in the case of voclosporin, when there are older, cheaper calcineurin inhibitors and I think I need one, I’m more likely to reach for one of the others.”

While GSK offers a patient assistance program for belimumab, which Dr. Blazer said she has used, physicians may not be aware of the program or have the resources in their offices to provide social work support for their patients.

“I have had patients who started it and ... continued to have a flare and needed to go on disability or leave their jobs, and they were just too concerned with the ongoing cost burden, and so I ended up taking them off the medication for that reason at their request,” she said.

The fact that Black patients have lupus nephritis more often than White patients do, as well as greater socioeconomic barriers, points to access to care and cost as major factors in why new drugs are not being used, Dr. Blazer said. “I think that understanding how we can improve access is going to be extremely important in getting more real-world data and getting more patients treated,” she said.

Treatment preference

A chart audit recently released by market research firm Spherix Global Insights highlighted a potential treatment preference for lupus nephritis. Use of voclosporin increased among rheumatologists and nephrologists, but patients with lupus nephritis under the care of rheumatologists were more likely to be treated with belimumab than voclosporin.

Dr. Saxena said he has experience with both and doesn’t have a preference, instead using factors other than experience when deciding the best treatment for patients. “For example, if there are nonrenal manifestations such as arthritis or rashes, I may lean towards belimumab, but if a more rapid reduction in proteinuria is important, I may lean towards voclosporin,” he said.

Dr. Thomas weighs the pros and cons of voclosporin and belimumab with the patient. “With many lupus nephritis scenarios, either drug may be a good choice and it comes down to patient preference. The main scenario where I would choose [voclosporin] over [belimumab] is in patients with [proteinuria of] 3 g protein/day or more,” he said, while belimumab would be the choice for a patient with “nonrenal manifestations of SLE in addition to their nephritis.”

For other rheumatologists, comfort level with belimumab may play a role. “We always had [belimumab] and we were always using [belimumab], and so it would make sense that like we would go for a med, again, that we’re really familiar with and we use,” Dr. Blanco said.

Dr. Blanco has prescribed belimumab, but had been using tacrolimus until recently. “I’ve been using tacrolimus since 2016. I’m probably going to lean on the [tacrolimus] rather than going to [belimumab], which works, but maybe it’s not the end-all, be-all in terms of lupus,” she said.

Although she hasn’t yet prescribed voclosporin, Dr. Blazer said she had “much more experience with belimumab.

“I’ve prescribed other calcineurin inhibitors in the past, and usually for a patient who’s very proteinuric and as an adjunct to that standard of care to try to bring down the proteinuria,” she said.

With belimumab, she would consider adding it to a patient with severe disease who has failed treatment with mycophenolate mofetil or cyclophosphamide and has a recurrent lupus nephritis flare. “It’s something I can use as an adjunct, and I think that I can get some extra benefit from it, and it also tends to be well tolerated,” Dr. Blazer said.

How patients are responding

Dr. Thomas’ patients have been responding well on voclosporin and belimumab. “I was an early adopter of [belimumab] and had patients with lupus nephritis do great on it, way before the FDA approval,” he said.

For voclosporin, Dr. Thomas highlighted the “incredibly rapid” proteinuria response. “I had a patient have marked reduction in proteinuria in just 2 weeks. Proteinuria reduction is the number one predictor of long-term better outcomes,” he said.

Many patients receiving mycophenolate and cyclophosphamide do not go into complete remission, while the clinical trials for voclosporin and belimumab had significantly higher rates of complete response and faster response rates, compared with older therapies. “That is what we need,” he said.

“These drugs are game changers in the treatment of lupus nephritis. In my mind, belimumab and voclosporin should be considered the standard of medical care treating lupus nephritis patients,” he added.

Dr. Blanco said her patients appear to like and are tolerating voclosporin and belimumab well, but because there are no pregnancy data on voclosporin, she may choose belimumab or tacrolimus for patients of reproductive age who are considering starting a family.

Patients with extrarenal symptoms tend to do particularly well with belimumab, such as those with arthritis and skin rash, Dr. Blazer said. “In my experience, as an adjunct with those standard of care medications, I have been able to maintain remission in my patients,” she said.

Dr. Saxena said both medications are “important options” for lupus nephritis in patients who don’t respond to standard therapy. “As more doctors utilize each medication and additional data is published, I’d expect an increase uptake in both medications in the future,” he said.

Dr. Blazer reported being a contributor to GSK’s SLE Educators’ Network and has been a consultant for Aurinia. Dr. Saxena reported being a consultant for GSK and Aurinia. Dr. Thomas reported being on the speakers bureau for GSK and Aurinia. Dr. Blanco reported having no relevant financial relationships with pharmaceutical companies.

More clinical guidance is needed for monitoring interstitial lung disease (ILD) in patients with rheumatoid arthritis, according to a new commentary.

Though ILD is a leading cause of death among patients with RA, these patients are not routinely screened for ILD, the authors say, and there are currently no guidelines on how to monitor ILD progression in patients with RA.

A.Prof Frank Gaillard, Radiopaedia.org

“ILD associated with rheumatoid arthritis is a disease for which there’s been very little research done, so it’s an area of rheumatology where there are many unknowns,” lead author Elizabeth R. Volkmann, MD, who codirects the connective tissue disease–related interstitial lung disease (CTD-ILD) program at University of California, Los Angeles, told this news organization.

The commentary was published in The Lancet Rheumatology.
 

Defining disease

One of the major unknowns is how to define the disease, she said. RA patients sometimes undergo imaging for other medical reasons, and interstitial lung abnormalities are incidentally detected. These patients can be classified as having “preclinical” or “subclinical” ILD, as they do not yet have symptoms; however, there is no consensus as to what these terms mean, the commentary authors write. “The other problem that we have with these terms is that it sometimes creates the perception that this is a nonworrisome feature of rheumatoid arthritis,” Dr. Volkmann said, although the condition should be followed closely.

“We know we can detect imaging features of ILD in people who may not yet have symptoms, and we need to know when to define a clinically important informality that requires follow-up or treatment,” added John M. Davis III, MD, a rheumatologist at the Mayo Clinic, Rochester, Minn. He was not involved with the work.

Mayo Clinic

Dr. Volkmann proposed eliminating the prefixes “pre” and “sub” when referring to ILD. “In other connective tissue diseases, like systemic sclerosis, for example, we can use the term ‘limited’ or ‘extensive’ ILD, based on the extent of involvement of the ILD on high-resolution computed tomography (HRCT) imaging,” she said. “This could potentially be something that is applied to how we classify patients with RA-ILD.”
 

Tracking ILD progression

Once ILD is identified, monitoring its progression poses challenges, as respiratory symptoms may be difficult to detect. RA patients may already be avoiding exercise because of joint pain, so they may not notice shortness of breath during physical activity, noted Jessica K. Gordon, MD, of the Hospital for Special Surgery, New York, in an interview with this news organization. She was not involved with the commentary. Cough is a potential symptom of ILD, but cough can also be the result of allergies, postnasal drip, or reflux, she said. Making the distinction between “preclinical” and symptomatic disease can be “complicated,” she added; “you may have to really dig.”

Hospital for Special Surgery

Additionally, there has been little research on the outcomes of patients with preclinical or subclinical ILD and clinical ILD, the commentary authors write. “It is therefore conceivable that some patients with rheumatoid arthritis diagnosed with preclinical or subclinical ILD could potentially have worse outcomes if both the rheumatoid arthritis and ILD are not monitored closely,” they note.

To better track RA-associated ILD for patients with and those without symptoms, the authors advocate for monitoring patients using pulmonary testing and CT scanning, as well as evaluating symptoms. How often these assessments should be conducted depends on the individual, they note. In her own practice, Dr. Volkmann sees patients every 3 months to evaluate their symptoms and conduct pulmonary function tests (PFTs). For patients early in the course of ILD, she orders HRCT imaging once per year.

For Dr. Davis, the frequency of follow-up depends on the severity of ILD. “For minimally symptomatic patients without compromised lung function, we would generally follow annually. For patients with symptomatic ILD on stable therapy, we may monitor every 6 months. For patients with active/progressive ILD, we would generally be following at least every 1-3 months,” he said.

Screening and future research

While there is no evidence to recommend screening patients for ILD using CT, there are certain risk factors for ILD in RA patients, including a history of smoking, male sex, and high RA disease activity despite antirheumatic treatment, Dr. Volkmann said. In both of their practices, Dr. Davis and Dr. Volkmann screen with RA via HRCT and PFTs for ILD for patients with known risk factors that predispose them to the lung condition and/or for patients who report respiratory symptoms.

National Jewish Health

“We still don’t have an algorithm [for screening patients], and that is a desperate need in this field,” added Joshua J. Solomon, MD, a pulmonologist at National Jewish Health, Denver, whose research focuses on RA-associated ILD. While recommendations state that all patients with scleroderma should be screened with CT, ILD incidence is lower among patients with RA, and thus these screening recommendations need to be narrowed, he said. But more research is needed to better fine tune recommendations, he said; “The only thing you can do is give some expert consensus until there are good data.”

Dr. Volkmann has received consulting and speaking fees from Boehringer Ingelheim and institutional support for performing studies on systemic sclerosis for Kadmon, Forbius, Boehringer Ingelheim, Horizon, and Prometheus. Dr. Gordon, Dr. Davis, and Dr. Solomon report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

More clinical guidance is needed for monitoring interstitial lung disease (ILD) in patients with rheumatoid arthritis, according to a new commentary.

Though ILD is a leading cause of death among patients with RA, these patients are not routinely screened for ILD, the authors say, and there are currently no guidelines on how to monitor ILD progression in patients with RA.

A.Prof Frank Gaillard, Radiopaedia.org

“ILD associated with rheumatoid arthritis is a disease for which there’s been very little research done, so it’s an area of rheumatology where there are many unknowns,” lead author Elizabeth R. Volkmann, MD, who codirects the connective tissue disease–related interstitial lung disease (CTD-ILD) program at University of California, Los Angeles, told this news organization.

The commentary was published in The Lancet Rheumatology.
 

Defining disease

One of the major unknowns is how to define the disease, she said. RA patients sometimes undergo imaging for other medical reasons, and interstitial lung abnormalities are incidentally detected. These patients can be classified as having “preclinical” or “subclinical” ILD, as they do not yet have symptoms; however, there is no consensus as to what these terms mean, the commentary authors write. “The other problem that we have with these terms is that it sometimes creates the perception that this is a nonworrisome feature of rheumatoid arthritis,” Dr. Volkmann said, although the condition should be followed closely.

“We know we can detect imaging features of ILD in people who may not yet have symptoms, and we need to know when to define a clinically important informality that requires follow-up or treatment,” added John M. Davis III, MD, a rheumatologist at the Mayo Clinic, Rochester, Minn. He was not involved with the work.

Mayo Clinic

Dr. Volkmann proposed eliminating the prefixes “pre” and “sub” when referring to ILD. “In other connective tissue diseases, like systemic sclerosis, for example, we can use the term ‘limited’ or ‘extensive’ ILD, based on the extent of involvement of the ILD on high-resolution computed tomography (HRCT) imaging,” she said. “This could potentially be something that is applied to how we classify patients with RA-ILD.”
 

Tracking ILD progression

Once ILD is identified, monitoring its progression poses challenges, as respiratory symptoms may be difficult to detect. RA patients may already be avoiding exercise because of joint pain, so they may not notice shortness of breath during physical activity, noted Jessica K. Gordon, MD, of the Hospital for Special Surgery, New York, in an interview with this news organization. She was not involved with the commentary. Cough is a potential symptom of ILD, but cough can also be the result of allergies, postnasal drip, or reflux, she said. Making the distinction between “preclinical” and symptomatic disease can be “complicated,” she added; “you may have to really dig.”

Hospital for Special Surgery

Additionally, there has been little research on the outcomes of patients with preclinical or subclinical ILD and clinical ILD, the commentary authors write. “It is therefore conceivable that some patients with rheumatoid arthritis diagnosed with preclinical or subclinical ILD could potentially have worse outcomes if both the rheumatoid arthritis and ILD are not monitored closely,” they note.

To better track RA-associated ILD for patients with and those without symptoms, the authors advocate for monitoring patients using pulmonary testing and CT scanning, as well as evaluating symptoms. How often these assessments should be conducted depends on the individual, they note. In her own practice, Dr. Volkmann sees patients every 3 months to evaluate their symptoms and conduct pulmonary function tests (PFTs). For patients early in the course of ILD, she orders HRCT imaging once per year.

For Dr. Davis, the frequency of follow-up depends on the severity of ILD. “For minimally symptomatic patients without compromised lung function, we would generally follow annually. For patients with symptomatic ILD on stable therapy, we may monitor every 6 months. For patients with active/progressive ILD, we would generally be following at least every 1-3 months,” he said.

Screening and future research

While there is no evidence to recommend screening patients for ILD using CT, there are certain risk factors for ILD in RA patients, including a history of smoking, male sex, and high RA disease activity despite antirheumatic treatment, Dr. Volkmann said. In both of their practices, Dr. Davis and Dr. Volkmann screen with RA via HRCT and PFTs for ILD for patients with known risk factors that predispose them to the lung condition and/or for patients who report respiratory symptoms.

National Jewish Health

“We still don’t have an algorithm [for screening patients], and that is a desperate need in this field,” added Joshua J. Solomon, MD, a pulmonologist at National Jewish Health, Denver, whose research focuses on RA-associated ILD. While recommendations state that all patients with scleroderma should be screened with CT, ILD incidence is lower among patients with RA, and thus these screening recommendations need to be narrowed, he said. But more research is needed to better fine tune recommendations, he said; “The only thing you can do is give some expert consensus until there are good data.”

Dr. Volkmann has received consulting and speaking fees from Boehringer Ingelheim and institutional support for performing studies on systemic sclerosis for Kadmon, Forbius, Boehringer Ingelheim, Horizon, and Prometheus. Dr. Gordon, Dr. Davis, and Dr. Solomon report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

More clinical guidance is needed for monitoring interstitial lung disease (ILD) in patients with rheumatoid arthritis, according to a new commentary.

Though ILD is a leading cause of death among patients with RA, these patients are not routinely screened for ILD, the authors say, and there are currently no guidelines on how to monitor ILD progression in patients with RA.

A.Prof Frank Gaillard, Radiopaedia.org

“ILD associated with rheumatoid arthritis is a disease for which there’s been very little research done, so it’s an area of rheumatology where there are many unknowns,” lead author Elizabeth R. Volkmann, MD, who codirects the connective tissue disease–related interstitial lung disease (CTD-ILD) program at University of California, Los Angeles, told this news organization.

The commentary was published in The Lancet Rheumatology.
 

Defining disease

One of the major unknowns is how to define the disease, she said. RA patients sometimes undergo imaging for other medical reasons, and interstitial lung abnormalities are incidentally detected. These patients can be classified as having “preclinical” or “subclinical” ILD, as they do not yet have symptoms; however, there is no consensus as to what these terms mean, the commentary authors write. “The other problem that we have with these terms is that it sometimes creates the perception that this is a nonworrisome feature of rheumatoid arthritis,” Dr. Volkmann said, although the condition should be followed closely.

“We know we can detect imaging features of ILD in people who may not yet have symptoms, and we need to know when to define a clinically important informality that requires follow-up or treatment,” added John M. Davis III, MD, a rheumatologist at the Mayo Clinic, Rochester, Minn. He was not involved with the work.

Mayo Clinic

Dr. Volkmann proposed eliminating the prefixes “pre” and “sub” when referring to ILD. “In other connective tissue diseases, like systemic sclerosis, for example, we can use the term ‘limited’ or ‘extensive’ ILD, based on the extent of involvement of the ILD on high-resolution computed tomography (HRCT) imaging,” she said. “This could potentially be something that is applied to how we classify patients with RA-ILD.”
 

Tracking ILD progression

Once ILD is identified, monitoring its progression poses challenges, as respiratory symptoms may be difficult to detect. RA patients may already be avoiding exercise because of joint pain, so they may not notice shortness of breath during physical activity, noted Jessica K. Gordon, MD, of the Hospital for Special Surgery, New York, in an interview with this news organization. She was not involved with the commentary. Cough is a potential symptom of ILD, but cough can also be the result of allergies, postnasal drip, or reflux, she said. Making the distinction between “preclinical” and symptomatic disease can be “complicated,” she added; “you may have to really dig.”

Hospital for Special Surgery

Additionally, there has been little research on the outcomes of patients with preclinical or subclinical ILD and clinical ILD, the commentary authors write. “It is therefore conceivable that some patients with rheumatoid arthritis diagnosed with preclinical or subclinical ILD could potentially have worse outcomes if both the rheumatoid arthritis and ILD are not monitored closely,” they note.

To better track RA-associated ILD for patients with and those without symptoms, the authors advocate for monitoring patients using pulmonary testing and CT scanning, as well as evaluating symptoms. How often these assessments should be conducted depends on the individual, they note. In her own practice, Dr. Volkmann sees patients every 3 months to evaluate their symptoms and conduct pulmonary function tests (PFTs). For patients early in the course of ILD, she orders HRCT imaging once per year.

For Dr. Davis, the frequency of follow-up depends on the severity of ILD. “For minimally symptomatic patients without compromised lung function, we would generally follow annually. For patients with symptomatic ILD on stable therapy, we may monitor every 6 months. For patients with active/progressive ILD, we would generally be following at least every 1-3 months,” he said.

Screening and future research

While there is no evidence to recommend screening patients for ILD using CT, there are certain risk factors for ILD in RA patients, including a history of smoking, male sex, and high RA disease activity despite antirheumatic treatment, Dr. Volkmann said. In both of their practices, Dr. Davis and Dr. Volkmann screen with RA via HRCT and PFTs for ILD for patients with known risk factors that predispose them to the lung condition and/or for patients who report respiratory symptoms.

National Jewish Health

“We still don’t have an algorithm [for screening patients], and that is a desperate need in this field,” added Joshua J. Solomon, MD, a pulmonologist at National Jewish Health, Denver, whose research focuses on RA-associated ILD. While recommendations state that all patients with scleroderma should be screened with CT, ILD incidence is lower among patients with RA, and thus these screening recommendations need to be narrowed, he said. But more research is needed to better fine tune recommendations, he said; “The only thing you can do is give some expert consensus until there are good data.”

Dr. Volkmann has received consulting and speaking fees from Boehringer Ingelheim and institutional support for performing studies on systemic sclerosis for Kadmon, Forbius, Boehringer Ingelheim, Horizon, and Prometheus. Dr. Gordon, Dr. Davis, and Dr. Solomon report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration approved sarilumab (Kevzara) on March 1 for the treatment of polymyalgia rheumatica (PMR) in adults who have had an inadequate response to corticosteroids or could not tolerate a corticosteroid taper, joint developers Sanofi and Regeneron announced. The drug is the first and only FDA-approved biologic treatment for this inflammatory rheumatic disease. 

The FDA previously approved sarilumab, an interleukin-6 receptor antagonist, in May 2017 for the treatment of moderate to severe active rheumatoid arthritis in adults who do not respond well or have an intolerance to disease-modifying antirheumatic drugs (DMARDs), like methotrexate.

Olivier Le Moal/Getty Images

The FDA approval for this new indication was based on results from the multicenter, phase 3 SAPHYR trial in patients with corticosteroid-resistant, active PMR. In the randomized, double-blind, placebo-controlled study, 59 participants received 200 mg of sarilumab plus a 14-week taper of corticosteroid treatment and 58 participants received placebo every 2 weeks along with a 52-week taper of corticosteroid treatment.

After 1 year, 28% of sarilumab patients achieved sustained remission, compared with 10% of the placebo group (P = .0193). This news organization previously reported these trial results in November when they were presented at the 2022 annual meeting of the American College of Rheumatology.

The most common adverse events in the sarilumab group were neutropenia (15%), leukopenia (7%), constipation (7%), pruritic rash (5%), myalgia (7%), fatigue (5%), and injection-site pruritus (5%). Two patients had serious adverse reactions of neutropenia, which resolved after discontinuing treatment.

“Polymyalgia rheumatica can be an incapacitating disease, causing painful disease flares in multiple parts of the bodies that leave people fatigued and unable to fully perform everyday activities. Corticosteroids have been the primary treatment to date, but many patients do not adequately respond to steroids or cannot be tapered off steroids, which puts such patients at risk of complications from long-term steroid therapy,” George D. Yancopolous, MD, PhD, president and chief scientific officer at Regeneron, said in the announcement. “With the approval of Kevzara for polymyalgia rheumatica, patients now have an FDA-approved treatment to help offer relief from the disabling symptoms of this disease and long-term dependence on steroids.”

A version of this article originally appeared on Medscape.com.

The Food and Drug Administration approved sarilumab (Kevzara) on March 1 for the treatment of polymyalgia rheumatica (PMR) in adults who have had an inadequate response to corticosteroids or could not tolerate a corticosteroid taper, joint developers Sanofi and Regeneron announced. The drug is the first and only FDA-approved biologic treatment for this inflammatory rheumatic disease. 

The FDA previously approved sarilumab, an interleukin-6 receptor antagonist, in May 2017 for the treatment of moderate to severe active rheumatoid arthritis in adults who do not respond well or have an intolerance to disease-modifying antirheumatic drugs (DMARDs), like methotrexate.

Olivier Le Moal/Getty Images

The FDA approval for this new indication was based on results from the multicenter, phase 3 SAPHYR trial in patients with corticosteroid-resistant, active PMR. In the randomized, double-blind, placebo-controlled study, 59 participants received 200 mg of sarilumab plus a 14-week taper of corticosteroid treatment and 58 participants received placebo every 2 weeks along with a 52-week taper of corticosteroid treatment.

After 1 year, 28% of sarilumab patients achieved sustained remission, compared with 10% of the placebo group (P = .0193). This news organization previously reported these trial results in November when they were presented at the 2022 annual meeting of the American College of Rheumatology.

The most common adverse events in the sarilumab group were neutropenia (15%), leukopenia (7%), constipation (7%), pruritic rash (5%), myalgia (7%), fatigue (5%), and injection-site pruritus (5%). Two patients had serious adverse reactions of neutropenia, which resolved after discontinuing treatment.

“Polymyalgia rheumatica can be an incapacitating disease, causing painful disease flares in multiple parts of the bodies that leave people fatigued and unable to fully perform everyday activities. Corticosteroids have been the primary treatment to date, but many patients do not adequately respond to steroids or cannot be tapered off steroids, which puts such patients at risk of complications from long-term steroid therapy,” George D. Yancopolous, MD, PhD, president and chief scientific officer at Regeneron, said in the announcement. “With the approval of Kevzara for polymyalgia rheumatica, patients now have an FDA-approved treatment to help offer relief from the disabling symptoms of this disease and long-term dependence on steroids.”

A version of this article originally appeared on Medscape.com.

The Food and Drug Administration approved sarilumab (Kevzara) on March 1 for the treatment of polymyalgia rheumatica (PMR) in adults who have had an inadequate response to corticosteroids or could not tolerate a corticosteroid taper, joint developers Sanofi and Regeneron announced. The drug is the first and only FDA-approved biologic treatment for this inflammatory rheumatic disease. 

The FDA previously approved sarilumab, an interleukin-6 receptor antagonist, in May 2017 for the treatment of moderate to severe active rheumatoid arthritis in adults who do not respond well or have an intolerance to disease-modifying antirheumatic drugs (DMARDs), like methotrexate.

Olivier Le Moal/Getty Images

The FDA approval for this new indication was based on results from the multicenter, phase 3 SAPHYR trial in patients with corticosteroid-resistant, active PMR. In the randomized, double-blind, placebo-controlled study, 59 participants received 200 mg of sarilumab plus a 14-week taper of corticosteroid treatment and 58 participants received placebo every 2 weeks along with a 52-week taper of corticosteroid treatment.

After 1 year, 28% of sarilumab patients achieved sustained remission, compared with 10% of the placebo group (P = .0193). This news organization previously reported these trial results in November when they were presented at the 2022 annual meeting of the American College of Rheumatology.

The most common adverse events in the sarilumab group were neutropenia (15%), leukopenia (7%), constipation (7%), pruritic rash (5%), myalgia (7%), fatigue (5%), and injection-site pruritus (5%). Two patients had serious adverse reactions of neutropenia, which resolved after discontinuing treatment.

“Polymyalgia rheumatica can be an incapacitating disease, causing painful disease flares in multiple parts of the bodies that leave people fatigued and unable to fully perform everyday activities. Corticosteroids have been the primary treatment to date, but many patients do not adequately respond to steroids or cannot be tapered off steroids, which puts such patients at risk of complications from long-term steroid therapy,” George D. Yancopolous, MD, PhD, president and chief scientific officer at Regeneron, said in the announcement. “With the approval of Kevzara for polymyalgia rheumatica, patients now have an FDA-approved treatment to help offer relief from the disabling symptoms of this disease and long-term dependence on steroids.”

A version of this article originally appeared on Medscape.com.

The often-delayed diagnosis of isolated nail psoriasis (NP), along with the possibility of a “reciprocal relationship” with psoriatic arthritis, “should serve as an impetus for dermatologists to improve their diagnostic accuracy,” investigators said in a research letter.

Diagnosis of isolated NP was delayed by almost 3 years among the 87 cases recorded and “arthritis was most often diagnosed concurrently with NP,” at a major nail referral center between Jan. 1, 2001, and Dec. 21, 2022, Michelle J. Chang of Drexel University, Philadelphia, and associates reported.

In what the authors say is, “the largest study documenting clinical and histologic features in patients with isolated NP,” the two most common clinical features were onycholysis and nail plate pitting, seen in 79% and 70% of cases, respectively. No other single feature had a prevalence higher than 28%.

The most frequent clinical dyad was onycholysis and pitting in 66% of patients, followed by onycholysis/nail thickening in 33% and onycholysis/splinter hemorrhage in 32%. The most common histologic features were parakeratosis in 79% and neutrophil infiltration in 48%, the investigators said.

Psoriatic arthritis (PsA), a focus of the study, occurred in 10 (11%) of the 87 individuals with isolated NP. Considering this finding, and “the close proximity between the nail apparatus and joint, we hypothesize a reciprocal relationship, with nail unit inflammation precipitating PsA,” Ms. Chang and associates wrote.

Senior author, Shari Lipner, MD, PhD, of the department of dermatology, Weill Cornell Medicine, New York, is a consultant for Ortho-Dermatologics, Hoth Therapeutics, and BelleTorus. Ms. Chang and the two other investigators had no conflicts of interest to declare.

 

The often-delayed diagnosis of isolated nail psoriasis (NP), along with the possibility of a “reciprocal relationship” with psoriatic arthritis, “should serve as an impetus for dermatologists to improve their diagnostic accuracy,” investigators said in a research letter.

Diagnosis of isolated NP was delayed by almost 3 years among the 87 cases recorded and “arthritis was most often diagnosed concurrently with NP,” at a major nail referral center between Jan. 1, 2001, and Dec. 21, 2022, Michelle J. Chang of Drexel University, Philadelphia, and associates reported.

In what the authors say is, “the largest study documenting clinical and histologic features in patients with isolated NP,” the two most common clinical features were onycholysis and nail plate pitting, seen in 79% and 70% of cases, respectively. No other single feature had a prevalence higher than 28%.

The most frequent clinical dyad was onycholysis and pitting in 66% of patients, followed by onycholysis/nail thickening in 33% and onycholysis/splinter hemorrhage in 32%. The most common histologic features were parakeratosis in 79% and neutrophil infiltration in 48%, the investigators said.

Psoriatic arthritis (PsA), a focus of the study, occurred in 10 (11%) of the 87 individuals with isolated NP. Considering this finding, and “the close proximity between the nail apparatus and joint, we hypothesize a reciprocal relationship, with nail unit inflammation precipitating PsA,” Ms. Chang and associates wrote.

Senior author, Shari Lipner, MD, PhD, of the department of dermatology, Weill Cornell Medicine, New York, is a consultant for Ortho-Dermatologics, Hoth Therapeutics, and BelleTorus. Ms. Chang and the two other investigators had no conflicts of interest to declare.

 

The often-delayed diagnosis of isolated nail psoriasis (NP), along with the possibility of a “reciprocal relationship” with psoriatic arthritis, “should serve as an impetus for dermatologists to improve their diagnostic accuracy,” investigators said in a research letter.

Diagnosis of isolated NP was delayed by almost 3 years among the 87 cases recorded and “arthritis was most often diagnosed concurrently with NP,” at a major nail referral center between Jan. 1, 2001, and Dec. 21, 2022, Michelle J. Chang of Drexel University, Philadelphia, and associates reported.

In what the authors say is, “the largest study documenting clinical and histologic features in patients with isolated NP,” the two most common clinical features were onycholysis and nail plate pitting, seen in 79% and 70% of cases, respectively. No other single feature had a prevalence higher than 28%.

The most frequent clinical dyad was onycholysis and pitting in 66% of patients, followed by onycholysis/nail thickening in 33% and onycholysis/splinter hemorrhage in 32%. The most common histologic features were parakeratosis in 79% and neutrophil infiltration in 48%, the investigators said.

Psoriatic arthritis (PsA), a focus of the study, occurred in 10 (11%) of the 87 individuals with isolated NP. Considering this finding, and “the close proximity between the nail apparatus and joint, we hypothesize a reciprocal relationship, with nail unit inflammation precipitating PsA,” Ms. Chang and associates wrote.

Senior author, Shari Lipner, MD, PhD, of the department of dermatology, Weill Cornell Medicine, New York, is a consultant for Ortho-Dermatologics, Hoth Therapeutics, and BelleTorus. Ms. Chang and the two other investigators had no conflicts of interest to declare.

 

Bacterial proteins in the bleeding gums of patients with periodontal disease (PD) and rheumatoid arthritis (RA) enter the bloodstream and trigger immune responses that may contribute to RA pathogenesis and disease flares, a new longitudinal study suggests.

The results suggest that PD involves repeated oral mucosa breakdowns with the release of citrullinated oral bacteria into the bloodstream and that these bacteria activate inflammatory monocytes in the inflamed RA synovium and in the blood of patients with RA. The bacteria also activate anti-citrullinated protein antibody (ACPA)–positive B cells, promoting affinity maturation and epitope spreading to citrullinated human antigens, the authors wrote.

“Our study discovered frequent and repeated episodes of oral bacteria in the blood of patients with periodontal disease and rheumatoid arthritis,” senior study author Dana E. Orange, MD, associate professor of clinical investigation at Rockefeller University, New York, said in an interview. “We saw that these bacteria were triggering an inflammatory [monocyte] response that is similar to what we see in the inflamed joints of patients with RA.

“RA patients are less likely to benefit from RA treatment if they have concurrent periodontal disease,” she said.

“RA patients tend to harbor cyclic citrullinated peptide [CCP] autoantibodies. Many groups have noted that CCP antibodies are very highly mutated, a signature of a B-cell/antibody response that has been stimulated over and over again,” Dr. Orange explained. “We found that CCP antibodies also bind the same oral bacteria we detected in the bloodstream. That patients with PD experience frequent, repeated episodes of oral bacteria in the blood is consistent with the very high level of mutation burden of CCP antibodies.”
 

Periodontal disease is a large problem among older adults

Periodontal disease ranges from gingivitis with swollen, red gums that may bleed, to periodontitis with gums pulling away from teeth, bone loss, and loose or lost teeth. PD is very prevalent in the United States, with some form of it occurring in 47% of people 30 years of age and older and in 70% of those 65 years and older, according to the Centers for Disease Control and Prevention.

PD is more common in people with RA who have detectable ACPAs, and that link implicates oral mucosal inflammation in RA pathogenesis.
 

Investigating whether PD leads to RA

At Rockefeller University, Dr. Orange and her colleagues followed five female patients with RA who were seropositive for CCP over the course of 1-4 years. Two had severe PD, and three showed no signs of PD. Each week, participants provided finger-stick blood samples for RNA sequencing and B-cell repertoire sequencing, reported changes in their medication and dental work, and completed questionnaires. They also underwent monthly physical exams that evaluated tenderness and swelling in 28 joints, and they provided additional samples during self-reported flares.

At Stanford (Calif.) University, researchers isolated plasmablasts from blood samples collected from 12 donors with anti-CPP+ RA and healthy donors. They also analyzed synovial fluid samples from 65 RA and OA patients.

In addition, University of Colorado researchers collected plasma samples from patients with RA and healthy donors, and they classified the gingival health of participants.

The researchers found that the patients with PD also had repeated flare-ups of oral bacteria in the blood, mainly from the Streptococcaceae family, suggesting that the oral mucosa repeatedly broke down and introduced bacteria into the bloodstream. In the blood, inflammatory immune cells targeted the bacteria and released ACPAs, which have been linked with RA.

“Even without dental procedures, patients with RA and periodontal disease experience repeated episodes of bacteremia,” Dr. Orange said. “While dental procedures are known to be associated with dissemination of oral bacteria into the bloodstream, we didn’t expect to see this happening so frequently and independent of dental procedures. We also had thought that people with oral bacteria in their blood would have symptoms such as fever or malaise, but they were asymptomatic.”
 

Experts welcome the results

“It is well established that oral health impacts overall health. In particular, the link between periodontal disease and chronic systemic diseases has been explored in many robust studies,” Chi T. Viet, MD, DDS, PhD, oral and maxillofacial surgeon and associate professor at the Loma Linda (Calif.) University School of Dentistry, told this news organization.

“The study ... highlights the importance of early treatment and prevention of oral health issues, as they can have devastating systemic sequelae,” added Dr. Viet, who was not involved in the study.

Devon Charlton, MD, MPH, director of rheumatology at the University of Pittsburgh Medical Center Regional Orthopedics in New Castle, Pa., advised patients and providers to team up to manage RA and PD.

“If the patient and provider aggressively treat periodontal disease and dental health in general, the patient decreases their risk of infection and inflammation, decreases the potential development of RA, and increases their future quality of life,” said Dr. Charlton, also not involved in the study.

However, findings from the study population may be difficult to generalize to other populations, he added.

Dr. Orange and her colleagues suggest further related research, including studies on whether treating PD makes RA easier to treat and whether the treatment of PD in patients whose RA is in clinical remission raises the likelihood of being able to discontinue therapy safely.

The study was supported through grant funding from the National Institutes of Health, the National Science Foundation, the Robertson Foundation, Rockefeller University, the Bernard and Irene Schwartz Foundation, the Iris and Junming Le Foundation, and the Rheumatology Research Foundation. Dr. Orange reports no relevant financial relationships. Several coauthors report financial relationships with the pharmaceutical industry. Dr. Viet and Dr. Charlton report no relevant financial relationships. All experts commented by email.

A version of this article first appeared on Medscape.com.

Bacterial proteins in the bleeding gums of patients with periodontal disease (PD) and rheumatoid arthritis (RA) enter the bloodstream and trigger immune responses that may contribute to RA pathogenesis and disease flares, a new longitudinal study suggests.

The results suggest that PD involves repeated oral mucosa breakdowns with the release of citrullinated oral bacteria into the bloodstream and that these bacteria activate inflammatory monocytes in the inflamed RA synovium and in the blood of patients with RA. The bacteria also activate anti-citrullinated protein antibody (ACPA)–positive B cells, promoting affinity maturation and epitope spreading to citrullinated human antigens, the authors wrote.

“Our study discovered frequent and repeated episodes of oral bacteria in the blood of patients with periodontal disease and rheumatoid arthritis,” senior study author Dana E. Orange, MD, associate professor of clinical investigation at Rockefeller University, New York, said in an interview. “We saw that these bacteria were triggering an inflammatory [monocyte] response that is similar to what we see in the inflamed joints of patients with RA.

“RA patients are less likely to benefit from RA treatment if they have concurrent periodontal disease,” she said.

“RA patients tend to harbor cyclic citrullinated peptide [CCP] autoantibodies. Many groups have noted that CCP antibodies are very highly mutated, a signature of a B-cell/antibody response that has been stimulated over and over again,” Dr. Orange explained. “We found that CCP antibodies also bind the same oral bacteria we detected in the bloodstream. That patients with PD experience frequent, repeated episodes of oral bacteria in the blood is consistent with the very high level of mutation burden of CCP antibodies.”
 

Periodontal disease is a large problem among older adults

Periodontal disease ranges from gingivitis with swollen, red gums that may bleed, to periodontitis with gums pulling away from teeth, bone loss, and loose or lost teeth. PD is very prevalent in the United States, with some form of it occurring in 47% of people 30 years of age and older and in 70% of those 65 years and older, according to the Centers for Disease Control and Prevention.

PD is more common in people with RA who have detectable ACPAs, and that link implicates oral mucosal inflammation in RA pathogenesis.
 

Investigating whether PD leads to RA

At Rockefeller University, Dr. Orange and her colleagues followed five female patients with RA who were seropositive for CCP over the course of 1-4 years. Two had severe PD, and three showed no signs of PD. Each week, participants provided finger-stick blood samples for RNA sequencing and B-cell repertoire sequencing, reported changes in their medication and dental work, and completed questionnaires. They also underwent monthly physical exams that evaluated tenderness and swelling in 28 joints, and they provided additional samples during self-reported flares.

At Stanford (Calif.) University, researchers isolated plasmablasts from blood samples collected from 12 donors with anti-CPP+ RA and healthy donors. They also analyzed synovial fluid samples from 65 RA and OA patients.

In addition, University of Colorado researchers collected plasma samples from patients with RA and healthy donors, and they classified the gingival health of participants.

The researchers found that the patients with PD also had repeated flare-ups of oral bacteria in the blood, mainly from the Streptococcaceae family, suggesting that the oral mucosa repeatedly broke down and introduced bacteria into the bloodstream. In the blood, inflammatory immune cells targeted the bacteria and released ACPAs, which have been linked with RA.

“Even without dental procedures, patients with RA and periodontal disease experience repeated episodes of bacteremia,” Dr. Orange said. “While dental procedures are known to be associated with dissemination of oral bacteria into the bloodstream, we didn’t expect to see this happening so frequently and independent of dental procedures. We also had thought that people with oral bacteria in their blood would have symptoms such as fever or malaise, but they were asymptomatic.”
 

Experts welcome the results

“It is well established that oral health impacts overall health. In particular, the link between periodontal disease and chronic systemic diseases has been explored in many robust studies,” Chi T. Viet, MD, DDS, PhD, oral and maxillofacial surgeon and associate professor at the Loma Linda (Calif.) University School of Dentistry, told this news organization.

“The study ... highlights the importance of early treatment and prevention of oral health issues, as they can have devastating systemic sequelae,” added Dr. Viet, who was not involved in the study.

Devon Charlton, MD, MPH, director of rheumatology at the University of Pittsburgh Medical Center Regional Orthopedics in New Castle, Pa., advised patients and providers to team up to manage RA and PD.

“If the patient and provider aggressively treat periodontal disease and dental health in general, the patient decreases their risk of infection and inflammation, decreases the potential development of RA, and increases their future quality of life,” said Dr. Charlton, also not involved in the study.

However, findings from the study population may be difficult to generalize to other populations, he added.

Dr. Orange and her colleagues suggest further related research, including studies on whether treating PD makes RA easier to treat and whether the treatment of PD in patients whose RA is in clinical remission raises the likelihood of being able to discontinue therapy safely.

The study was supported through grant funding from the National Institutes of Health, the National Science Foundation, the Robertson Foundation, Rockefeller University, the Bernard and Irene Schwartz Foundation, the Iris and Junming Le Foundation, and the Rheumatology Research Foundation. Dr. Orange reports no relevant financial relationships. Several coauthors report financial relationships with the pharmaceutical industry. Dr. Viet and Dr. Charlton report no relevant financial relationships. All experts commented by email.

A version of this article first appeared on Medscape.com.

Bacterial proteins in the bleeding gums of patients with periodontal disease (PD) and rheumatoid arthritis (RA) enter the bloodstream and trigger immune responses that may contribute to RA pathogenesis and disease flares, a new longitudinal study suggests.

The results suggest that PD involves repeated oral mucosa breakdowns with the release of citrullinated oral bacteria into the bloodstream and that these bacteria activate inflammatory monocytes in the inflamed RA synovium and in the blood of patients with RA. The bacteria also activate anti-citrullinated protein antibody (ACPA)–positive B cells, promoting affinity maturation and epitope spreading to citrullinated human antigens, the authors wrote.

“Our study discovered frequent and repeated episodes of oral bacteria in the blood of patients with periodontal disease and rheumatoid arthritis,” senior study author Dana E. Orange, MD, associate professor of clinical investigation at Rockefeller University, New York, said in an interview. “We saw that these bacteria were triggering an inflammatory [monocyte] response that is similar to what we see in the inflamed joints of patients with RA.

“RA patients are less likely to benefit from RA treatment if they have concurrent periodontal disease,” she said.

“RA patients tend to harbor cyclic citrullinated peptide [CCP] autoantibodies. Many groups have noted that CCP antibodies are very highly mutated, a signature of a B-cell/antibody response that has been stimulated over and over again,” Dr. Orange explained. “We found that CCP antibodies also bind the same oral bacteria we detected in the bloodstream. That patients with PD experience frequent, repeated episodes of oral bacteria in the blood is consistent with the very high level of mutation burden of CCP antibodies.”
 

Periodontal disease is a large problem among older adults

Periodontal disease ranges from gingivitis with swollen, red gums that may bleed, to periodontitis with gums pulling away from teeth, bone loss, and loose or lost teeth. PD is very prevalent in the United States, with some form of it occurring in 47% of people 30 years of age and older and in 70% of those 65 years and older, according to the Centers for Disease Control and Prevention.

PD is more common in people with RA who have detectable ACPAs, and that link implicates oral mucosal inflammation in RA pathogenesis.
 

Investigating whether PD leads to RA

At Rockefeller University, Dr. Orange and her colleagues followed five female patients with RA who were seropositive for CCP over the course of 1-4 years. Two had severe PD, and three showed no signs of PD. Each week, participants provided finger-stick blood samples for RNA sequencing and B-cell repertoire sequencing, reported changes in their medication and dental work, and completed questionnaires. They also underwent monthly physical exams that evaluated tenderness and swelling in 28 joints, and they provided additional samples during self-reported flares.

At Stanford (Calif.) University, researchers isolated plasmablasts from blood samples collected from 12 donors with anti-CPP+ RA and healthy donors. They also analyzed synovial fluid samples from 65 RA and OA patients.

In addition, University of Colorado researchers collected plasma samples from patients with RA and healthy donors, and they classified the gingival health of participants.

The researchers found that the patients with PD also had repeated flare-ups of oral bacteria in the blood, mainly from the Streptococcaceae family, suggesting that the oral mucosa repeatedly broke down and introduced bacteria into the bloodstream. In the blood, inflammatory immune cells targeted the bacteria and released ACPAs, which have been linked with RA.

“Even without dental procedures, patients with RA and periodontal disease experience repeated episodes of bacteremia,” Dr. Orange said. “While dental procedures are known to be associated with dissemination of oral bacteria into the bloodstream, we didn’t expect to see this happening so frequently and independent of dental procedures. We also had thought that people with oral bacteria in their blood would have symptoms such as fever or malaise, but they were asymptomatic.”
 

Experts welcome the results

“It is well established that oral health impacts overall health. In particular, the link between periodontal disease and chronic systemic diseases has been explored in many robust studies,” Chi T. Viet, MD, DDS, PhD, oral and maxillofacial surgeon and associate professor at the Loma Linda (Calif.) University School of Dentistry, told this news organization.

“The study ... highlights the importance of early treatment and prevention of oral health issues, as they can have devastating systemic sequelae,” added Dr. Viet, who was not involved in the study.

Devon Charlton, MD, MPH, director of rheumatology at the University of Pittsburgh Medical Center Regional Orthopedics in New Castle, Pa., advised patients and providers to team up to manage RA and PD.

“If the patient and provider aggressively treat periodontal disease and dental health in general, the patient decreases their risk of infection and inflammation, decreases the potential development of RA, and increases their future quality of life,” said Dr. Charlton, also not involved in the study.

However, findings from the study population may be difficult to generalize to other populations, he added.

Dr. Orange and her colleagues suggest further related research, including studies on whether treating PD makes RA easier to treat and whether the treatment of PD in patients whose RA is in clinical remission raises the likelihood of being able to discontinue therapy safely.

The study was supported through grant funding from the National Institutes of Health, the National Science Foundation, the Robertson Foundation, Rockefeller University, the Bernard and Irene Schwartz Foundation, the Iris and Junming Le Foundation, and the Rheumatology Research Foundation. Dr. Orange reports no relevant financial relationships. Several coauthors report financial relationships with the pharmaceutical industry. Dr. Viet and Dr. Charlton report no relevant financial relationships. All experts commented by email.

A version of this article first appeared on Medscape.com.

While most providers think that biosimilars will positively impact care, few feel that the economic benefits of biosimilars to date are enough to motivate switching.

Fuse/Thinkstock

In a new survey of over 350 dermatologists, gastroenterologists, ophthalmologists, and rheumatologists, clinicians shared their opinions on the rapidly evolving landscape of biosimilars, detailing top concerns about prescribing these medications and how they presently use biosimilars in clinical practice. Across all specialties, providers said they would be most likely to prescribe biosimilars to new patients or if a patient’s health plan mandated the switch. Most providers listed concerns about biosimilar efficacy and lack of economic benefit as the main barriers to adoption of biosimilars in clinical practice.

Cardinal Health, a health care services company based in Dublin, Ohio, conducted the surveys from July through October 2022.
 

Rheumatologists want cost-savings for patients

2023 is gearing up to be a big year for biosimilars for inflammatory diseases, with at least eight adalimumab biosimilars entering the market in the United States. Amjevita, manufactured by Amgen, was the first to become commercially available on Jan. 31. Out of 103 surveyed rheumatologists, 62% said they were very comfortable prescribing biosimilars to patients, and 32% said they were somewhat comfortable. Providers said they would be most likely to prescribe a biosimilar to new patients (40%) or if biosimilars were mandated by a patient’s health plan (41%). Nearly one-third (31%) of rheumatologists said that a discount of 21%-30% from a reference product would be necessary to consider switching a patient to a biosimilar.

There are several reasons why a rheumatologist might be wary of switching patients to biosimilars, said Marcus Snow, MD, chair of the American College of Rheumatology’s Committee on Rheumatologic Care. “Rheumatologists will always express concern about changing medications that work well for their patients. It is not ideal to ‘force switch’ to a different product, even if it is almost identical,” he told this news organization in an email. “Also, we must remember that a patient on a biologic has failed traditional medications, which speaks to the struggle a patient must endure to get their disease under control. Fail-first situations can cause a rheumatologist to be initially resistant or hesitant to any changes.”

The top concerns among rheumatologists about prescribing biosimilars were medication efficacy (36%), lack of economic benefit (24%), and evaluating when to prescribe a biosimilar versus a reference product (17%). For adalimumab biosimilars, rheumatologists said that interchangeability – a regulatory designation where a biosimilar can be automatically substituted for its reference product at the pharmacy – and citrate-free formulation were the most important product attributes. Sixty-four percent of providers also noted that patient out-of-pocket cost would be key when deciding to prescribe an adalimumab biosimilar.

“There needs to be a true reduction in price, to change providers’ opinions on the economic benefits of biosimilars – in the system generally and for the patient,” Dr. Snow said. “Things will get there eventually, but it is not there yet, based on the list prices we see for some biosimilars.”
 

Gastroenterologists emphasize patient education

Gastroenterology is another specialty to be affected by the influx of adalimumab biosimilars. Out of 72 surveyed gastroenterologists, 86% said they were very comfortable prescribing biosimilars. About half (49%) said they would be most likely to prescribe a biosimilar to patients with health plans mandating a biosimilar. More than 60% of surveyed gastroenterologists said that biosimilars would positively impact care; providers were divided on the current economic benefits of biosimilars, with 36% saying that the current discounts on biosimilars versus reference products were not favorable enough to motivate switching, and 35% stating that they were. A total of 40% of surveyed providers said that savings of 21%-30%, compared with savings of a reference product, would motivate them to switch patients to a biosimilar, with all other clinical factors being equal.

Gastroenterologists said that, along with the efficacy and cost savings of biosimilars, providing patient education (18%) was a top concern when prescribing biosimilars. Eighty-four percent of respondents said that educating patients about biosimilars as safe and effective treatment options was at least somewhat important. Nearly all participants (99%) cited device ease-of-use as at least somewhat important when considering prescribing adalimumab biosimilars, in addition to interchangeability (97%) and citrate-free formulation (93%).

“Despite general acceptance of biosimilars, there remains some uncertainty regarding their place in the current gastroenterology landscape,” wrote Vivek Kaul, MD, a professor of medicine at the University of Rochester (N.Y.) Medical Center, in the report. “This is likely because only half of the survey respondents believed that biosimilars will positively impact gastroenterology care, further highlighting the ongoing need for real-world data and incorporation of biosimilar use and interchangeability into clinical guidelines.”

Few dermatologists currently prescribe biosimilars

Eight out of ten dermatologists reported being at least somewhat comfortable prescribing biosimilars to patients, though fewer than 20% said they had prescribed a biosimilar in the past year. This indicates limited adoption of infliximab biosimilars, which were the only biosimilars with a dermatologic indication available in 2022, Alex Gross, MD, a dermatologist in Cumming, Ga., noted in his featured commentary in the report. Just 15% of respondents disagreed that biosimilars would have a positive impact on care, and 41% said they were excited about new biosimilars becoming available.

About half (47%) of dermatologists thought the economic benefits of biosimilars were not strong enough to motivate switching patients from reference products. Twenty-nine percent of respondents said that discounts of 21%-30% from a reference product would motivate them to switch patients to a biosimilar, with all other clinical factors being equal, while 20% said they were not likely to prescribe a biosimilar regardless of savings.

Dermatologists may be concerned that these cost savings may not be passed onto patients, said Alison Ehrlich, MD, a dermatologist in Washington, in an email to this news organization. Patient out-of-pocket cost savings would need to be “both significant and transparent” to begin to change providers’ minds, she noted.

Biosimilar efficacy was a top concern for 48% of dermatologists, while 13% said their main concern around prescribing biosimilars was lack of payer adoption. At least 95% of providers said that device ease-of-use and interchangeability were the most important attributes when considering adalimumab biosimilars. Nearly two-thirds (65%) reported that patient out-of-pocket cost would be key when deciding to prescribe an adalimumab biosimilar.

If both patients and providers are informed on biosimilar use and there are cost benefits, dermatologists’ opinions may become more favorable toward biosimilars, but that will take time, Dr. Ehrlich said. “We are very early in the game for biosimilar use in dermatology,” she added.
 

Ophthalmologists remain wary

Biosimilars have been relatively new to ophthalmology, with the first ranibizumab biosimilar becoming commercially available in July 2022. In the survey, 64 retina specialists were asked different questions than participants from other specialties to gauge ophthalmologists› familiarity with the biosimilars approval process and their overall comfort prescribing these medications. The primary concerns with prescribing biosimilars among respondents was payer coverage (52%), being uncomfortable with biosimilars from a clinical standpoint (48%), and administrative barriers (45%), such as prior authorization. Despite this lack of comfort with biosimilars, two-thirds of participants thought the U.S. Food and Drug Administration approval process for these medications was sufficient to evaluate their efficacy and safety. Still, fewer than half (48%) of providers said they do or would prescribe biosimilars.

George Williams, MD, a spokesperson for the American Academy of Ophthalmology, noted that the FDA approval process for biosimilars was not as rigorous as for the respective reference product, and fewer patients are followed over a shorter time period. “Since anti–[vascular endothelial growth factor (VEGF)] therapy for indications such as neovascular age-related macular degeneration continues indefinitely over years, ophthalmologists may have concerns about the long-term efficacy and safety when applied to larger real-world populations. Ophthalmologists are well aware of safety issues with VEGF inhibitors arising after FDA approval,” he told this news organization in an email.

When asked about the likelihood of using either aflibercept or ranibizumab biosimilars in their clinical practice once commercially available, 70% of ophthalmologists said they would be at least somewhat likely to prescribe aflibercept biosimilars, and 64% said they would be at least somewhat likely to prescribe ranibizumab biosimilars. About half of respondents said they would not likely switch a currently stable patient on either aflibercept or ranibizumab to the corresponding biosimilar. More than half of ophthalmologists (56%) said they would prescribe a biosimilar only if it had an interchangeability designation.

Out of all four specialties, ophthalmologists more frequently reported that higher discounts from a reference product would be necessary to consider switching a patient to a biosimilar. Currently, many ophthalmologists are comfortable with the off-label use of bevacizumab (Avastin) for treating wet age-related macular degeneration, which also offers more cost savings than any currently available biosimilar on the market, Dr. Williams said.

While the limited number of respondents makes it difficult to draw concrete conclusions, Dr. Williams emphasized that the AAO supported the use of biosimilars. “We believe that with clinical experience ophthalmic biosimilars will become useful therapeutic agents,” he noted.

A version of this article first appeared on Medscape.com.

While most providers think that biosimilars will positively impact care, few feel that the economic benefits of biosimilars to date are enough to motivate switching.

Fuse/Thinkstock

In a new survey of over 350 dermatologists, gastroenterologists, ophthalmologists, and rheumatologists, clinicians shared their opinions on the rapidly evolving landscape of biosimilars, detailing top concerns about prescribing these medications and how they presently use biosimilars in clinical practice. Across all specialties, providers said they would be most likely to prescribe biosimilars to new patients or if a patient’s health plan mandated the switch. Most providers listed concerns about biosimilar efficacy and lack of economic benefit as the main barriers to adoption of biosimilars in clinical practice.

Cardinal Health, a health care services company based in Dublin, Ohio, conducted the surveys from July through October 2022.
 

Rheumatologists want cost-savings for patients

2023 is gearing up to be a big year for biosimilars for inflammatory diseases, with at least eight adalimumab biosimilars entering the market in the United States. Amjevita, manufactured by Amgen, was the first to become commercially available on Jan. 31. Out of 103 surveyed rheumatologists, 62% said they were very comfortable prescribing biosimilars to patients, and 32% said they were somewhat comfortable. Providers said they would be most likely to prescribe a biosimilar to new patients (40%) or if biosimilars were mandated by a patient’s health plan (41%). Nearly one-third (31%) of rheumatologists said that a discount of 21%-30% from a reference product would be necessary to consider switching a patient to a biosimilar.

There are several reasons why a rheumatologist might be wary of switching patients to biosimilars, said Marcus Snow, MD, chair of the American College of Rheumatology’s Committee on Rheumatologic Care. “Rheumatologists will always express concern about changing medications that work well for their patients. It is not ideal to ‘force switch’ to a different product, even if it is almost identical,” he told this news organization in an email. “Also, we must remember that a patient on a biologic has failed traditional medications, which speaks to the struggle a patient must endure to get their disease under control. Fail-first situations can cause a rheumatologist to be initially resistant or hesitant to any changes.”

The top concerns among rheumatologists about prescribing biosimilars were medication efficacy (36%), lack of economic benefit (24%), and evaluating when to prescribe a biosimilar versus a reference product (17%). For adalimumab biosimilars, rheumatologists said that interchangeability – a regulatory designation where a biosimilar can be automatically substituted for its reference product at the pharmacy – and citrate-free formulation were the most important product attributes. Sixty-four percent of providers also noted that patient out-of-pocket cost would be key when deciding to prescribe an adalimumab biosimilar.

“There needs to be a true reduction in price, to change providers’ opinions on the economic benefits of biosimilars – in the system generally and for the patient,” Dr. Snow said. “Things will get there eventually, but it is not there yet, based on the list prices we see for some biosimilars.”
 

Gastroenterologists emphasize patient education

Gastroenterology is another specialty to be affected by the influx of adalimumab biosimilars. Out of 72 surveyed gastroenterologists, 86% said they were very comfortable prescribing biosimilars. About half (49%) said they would be most likely to prescribe a biosimilar to patients with health plans mandating a biosimilar. More than 60% of surveyed gastroenterologists said that biosimilars would positively impact care; providers were divided on the current economic benefits of biosimilars, with 36% saying that the current discounts on biosimilars versus reference products were not favorable enough to motivate switching, and 35% stating that they were. A total of 40% of surveyed providers said that savings of 21%-30%, compared with savings of a reference product, would motivate them to switch patients to a biosimilar, with all other clinical factors being equal.

Gastroenterologists said that, along with the efficacy and cost savings of biosimilars, providing patient education (18%) was a top concern when prescribing biosimilars. Eighty-four percent of respondents said that educating patients about biosimilars as safe and effective treatment options was at least somewhat important. Nearly all participants (99%) cited device ease-of-use as at least somewhat important when considering prescribing adalimumab biosimilars, in addition to interchangeability (97%) and citrate-free formulation (93%).

“Despite general acceptance of biosimilars, there remains some uncertainty regarding their place in the current gastroenterology landscape,” wrote Vivek Kaul, MD, a professor of medicine at the University of Rochester (N.Y.) Medical Center, in the report. “This is likely because only half of the survey respondents believed that biosimilars will positively impact gastroenterology care, further highlighting the ongoing need for real-world data and incorporation of biosimilar use and interchangeability into clinical guidelines.”

Few dermatologists currently prescribe biosimilars

Eight out of ten dermatologists reported being at least somewhat comfortable prescribing biosimilars to patients, though fewer than 20% said they had prescribed a biosimilar in the past year. This indicates limited adoption of infliximab biosimilars, which were the only biosimilars with a dermatologic indication available in 2022, Alex Gross, MD, a dermatologist in Cumming, Ga., noted in his featured commentary in the report. Just 15% of respondents disagreed that biosimilars would have a positive impact on care, and 41% said they were excited about new biosimilars becoming available.

About half (47%) of dermatologists thought the economic benefits of biosimilars were not strong enough to motivate switching patients from reference products. Twenty-nine percent of respondents said that discounts of 21%-30% from a reference product would motivate them to switch patients to a biosimilar, with all other clinical factors being equal, while 20% said they were not likely to prescribe a biosimilar regardless of savings.

Dermatologists may be concerned that these cost savings may not be passed onto patients, said Alison Ehrlich, MD, a dermatologist in Washington, in an email to this news organization. Patient out-of-pocket cost savings would need to be “both significant and transparent” to begin to change providers’ minds, she noted.

Biosimilar efficacy was a top concern for 48% of dermatologists, while 13% said their main concern around prescribing biosimilars was lack of payer adoption. At least 95% of providers said that device ease-of-use and interchangeability were the most important attributes when considering adalimumab biosimilars. Nearly two-thirds (65%) reported that patient out-of-pocket cost would be key when deciding to prescribe an adalimumab biosimilar.

If both patients and providers are informed on biosimilar use and there are cost benefits, dermatologists’ opinions may become more favorable toward biosimilars, but that will take time, Dr. Ehrlich said. “We are very early in the game for biosimilar use in dermatology,” she added.
 

Ophthalmologists remain wary

Biosimilars have been relatively new to ophthalmology, with the first ranibizumab biosimilar becoming commercially available in July 2022. In the survey, 64 retina specialists were asked different questions than participants from other specialties to gauge ophthalmologists› familiarity with the biosimilars approval process and their overall comfort prescribing these medications. The primary concerns with prescribing biosimilars among respondents was payer coverage (52%), being uncomfortable with biosimilars from a clinical standpoint (48%), and administrative barriers (45%), such as prior authorization. Despite this lack of comfort with biosimilars, two-thirds of participants thought the U.S. Food and Drug Administration approval process for these medications was sufficient to evaluate their efficacy and safety. Still, fewer than half (48%) of providers said they do or would prescribe biosimilars.

George Williams, MD, a spokesperson for the American Academy of Ophthalmology, noted that the FDA approval process for biosimilars was not as rigorous as for the respective reference product, and fewer patients are followed over a shorter time period. “Since anti–[vascular endothelial growth factor (VEGF)] therapy for indications such as neovascular age-related macular degeneration continues indefinitely over years, ophthalmologists may have concerns about the long-term efficacy and safety when applied to larger real-world populations. Ophthalmologists are well aware of safety issues with VEGF inhibitors arising after FDA approval,” he told this news organization in an email.

When asked about the likelihood of using either aflibercept or ranibizumab biosimilars in their clinical practice once commercially available, 70% of ophthalmologists said they would be at least somewhat likely to prescribe aflibercept biosimilars, and 64% said they would be at least somewhat likely to prescribe ranibizumab biosimilars. About half of respondents said they would not likely switch a currently stable patient on either aflibercept or ranibizumab to the corresponding biosimilar. More than half of ophthalmologists (56%) said they would prescribe a biosimilar only if it had an interchangeability designation.

Out of all four specialties, ophthalmologists more frequently reported that higher discounts from a reference product would be necessary to consider switching a patient to a biosimilar. Currently, many ophthalmologists are comfortable with the off-label use of bevacizumab (Avastin) for treating wet age-related macular degeneration, which also offers more cost savings than any currently available biosimilar on the market, Dr. Williams said.

While the limited number of respondents makes it difficult to draw concrete conclusions, Dr. Williams emphasized that the AAO supported the use of biosimilars. “We believe that with clinical experience ophthalmic biosimilars will become useful therapeutic agents,” he noted.

A version of this article first appeared on Medscape.com.

While most providers think that biosimilars will positively impact care, few feel that the economic benefits of biosimilars to date are enough to motivate switching.

Fuse/Thinkstock

In a new survey of over 350 dermatologists, gastroenterologists, ophthalmologists, and rheumatologists, clinicians shared their opinions on the rapidly evolving landscape of biosimilars, detailing top concerns about prescribing these medications and how they presently use biosimilars in clinical practice. Across all specialties, providers said they would be most likely to prescribe biosimilars to new patients or if a patient’s health plan mandated the switch. Most providers listed concerns about biosimilar efficacy and lack of economic benefit as the main barriers to adoption of biosimilars in clinical practice.

Cardinal Health, a health care services company based in Dublin, Ohio, conducted the surveys from July through October 2022.
 

Rheumatologists want cost-savings for patients

2023 is gearing up to be a big year for biosimilars for inflammatory diseases, with at least eight adalimumab biosimilars entering the market in the United States. Amjevita, manufactured by Amgen, was the first to become commercially available on Jan. 31. Out of 103 surveyed rheumatologists, 62% said they were very comfortable prescribing biosimilars to patients, and 32% said they were somewhat comfortable. Providers said they would be most likely to prescribe a biosimilar to new patients (40%) or if biosimilars were mandated by a patient’s health plan (41%). Nearly one-third (31%) of rheumatologists said that a discount of 21%-30% from a reference product would be necessary to consider switching a patient to a biosimilar.

There are several reasons why a rheumatologist might be wary of switching patients to biosimilars, said Marcus Snow, MD, chair of the American College of Rheumatology’s Committee on Rheumatologic Care. “Rheumatologists will always express concern about changing medications that work well for their patients. It is not ideal to ‘force switch’ to a different product, even if it is almost identical,” he told this news organization in an email. “Also, we must remember that a patient on a biologic has failed traditional medications, which speaks to the struggle a patient must endure to get their disease under control. Fail-first situations can cause a rheumatologist to be initially resistant or hesitant to any changes.”

The top concerns among rheumatologists about prescribing biosimilars were medication efficacy (36%), lack of economic benefit (24%), and evaluating when to prescribe a biosimilar versus a reference product (17%). For adalimumab biosimilars, rheumatologists said that interchangeability – a regulatory designation where a biosimilar can be automatically substituted for its reference product at the pharmacy – and citrate-free formulation were the most important product attributes. Sixty-four percent of providers also noted that patient out-of-pocket cost would be key when deciding to prescribe an adalimumab biosimilar.

“There needs to be a true reduction in price, to change providers’ opinions on the economic benefits of biosimilars – in the system generally and for the patient,” Dr. Snow said. “Things will get there eventually, but it is not there yet, based on the list prices we see for some biosimilars.”
 

Gastroenterologists emphasize patient education

Gastroenterology is another specialty to be affected by the influx of adalimumab biosimilars. Out of 72 surveyed gastroenterologists, 86% said they were very comfortable prescribing biosimilars. About half (49%) said they would be most likely to prescribe a biosimilar to patients with health plans mandating a biosimilar. More than 60% of surveyed gastroenterologists said that biosimilars would positively impact care; providers were divided on the current economic benefits of biosimilars, with 36% saying that the current discounts on biosimilars versus reference products were not favorable enough to motivate switching, and 35% stating that they were. A total of 40% of surveyed providers said that savings of 21%-30%, compared with savings of a reference product, would motivate them to switch patients to a biosimilar, with all other clinical factors being equal.

Gastroenterologists said that, along with the efficacy and cost savings of biosimilars, providing patient education (18%) was a top concern when prescribing biosimilars. Eighty-four percent of respondents said that educating patients about biosimilars as safe and effective treatment options was at least somewhat important. Nearly all participants (99%) cited device ease-of-use as at least somewhat important when considering prescribing adalimumab biosimilars, in addition to interchangeability (97%) and citrate-free formulation (93%).

“Despite general acceptance of biosimilars, there remains some uncertainty regarding their place in the current gastroenterology landscape,” wrote Vivek Kaul, MD, a professor of medicine at the University of Rochester (N.Y.) Medical Center, in the report. “This is likely because only half of the survey respondents believed that biosimilars will positively impact gastroenterology care, further highlighting the ongoing need for real-world data and incorporation of biosimilar use and interchangeability into clinical guidelines.”

Few dermatologists currently prescribe biosimilars

Eight out of ten dermatologists reported being at least somewhat comfortable prescribing biosimilars to patients, though fewer than 20% said they had prescribed a biosimilar in the past year. This indicates limited adoption of infliximab biosimilars, which were the only biosimilars with a dermatologic indication available in 2022, Alex Gross, MD, a dermatologist in Cumming, Ga., noted in his featured commentary in the report. Just 15% of respondents disagreed that biosimilars would have a positive impact on care, and 41% said they were excited about new biosimilars becoming available.

About half (47%) of dermatologists thought the economic benefits of biosimilars were not strong enough to motivate switching patients from reference products. Twenty-nine percent of respondents said that discounts of 21%-30% from a reference product would motivate them to switch patients to a biosimilar, with all other clinical factors being equal, while 20% said they were not likely to prescribe a biosimilar regardless of savings.

Dermatologists may be concerned that these cost savings may not be passed onto patients, said Alison Ehrlich, MD, a dermatologist in Washington, in an email to this news organization. Patient out-of-pocket cost savings would need to be “both significant and transparent” to begin to change providers’ minds, she noted.

Biosimilar efficacy was a top concern for 48% of dermatologists, while 13% said their main concern around prescribing biosimilars was lack of payer adoption. At least 95% of providers said that device ease-of-use and interchangeability were the most important attributes when considering adalimumab biosimilars. Nearly two-thirds (65%) reported that patient out-of-pocket cost would be key when deciding to prescribe an adalimumab biosimilar.

If both patients and providers are informed on biosimilar use and there are cost benefits, dermatologists’ opinions may become more favorable toward biosimilars, but that will take time, Dr. Ehrlich said. “We are very early in the game for biosimilar use in dermatology,” she added.
 

Ophthalmologists remain wary

Biosimilars have been relatively new to ophthalmology, with the first ranibizumab biosimilar becoming commercially available in July 2022. In the survey, 64 retina specialists were asked different questions than participants from other specialties to gauge ophthalmologists› familiarity with the biosimilars approval process and their overall comfort prescribing these medications. The primary concerns with prescribing biosimilars among respondents was payer coverage (52%), being uncomfortable with biosimilars from a clinical standpoint (48%), and administrative barriers (45%), such as prior authorization. Despite this lack of comfort with biosimilars, two-thirds of participants thought the U.S. Food and Drug Administration approval process for these medications was sufficient to evaluate their efficacy and safety. Still, fewer than half (48%) of providers said they do or would prescribe biosimilars.

George Williams, MD, a spokesperson for the American Academy of Ophthalmology, noted that the FDA approval process for biosimilars was not as rigorous as for the respective reference product, and fewer patients are followed over a shorter time period. “Since anti–[vascular endothelial growth factor (VEGF)] therapy for indications such as neovascular age-related macular degeneration continues indefinitely over years, ophthalmologists may have concerns about the long-term efficacy and safety when applied to larger real-world populations. Ophthalmologists are well aware of safety issues with VEGF inhibitors arising after FDA approval,” he told this news organization in an email.

When asked about the likelihood of using either aflibercept or ranibizumab biosimilars in their clinical practice once commercially available, 70% of ophthalmologists said they would be at least somewhat likely to prescribe aflibercept biosimilars, and 64% said they would be at least somewhat likely to prescribe ranibizumab biosimilars. About half of respondents said they would not likely switch a currently stable patient on either aflibercept or ranibizumab to the corresponding biosimilar. More than half of ophthalmologists (56%) said they would prescribe a biosimilar only if it had an interchangeability designation.

Out of all four specialties, ophthalmologists more frequently reported that higher discounts from a reference product would be necessary to consider switching a patient to a biosimilar. Currently, many ophthalmologists are comfortable with the off-label use of bevacizumab (Avastin) for treating wet age-related macular degeneration, which also offers more cost savings than any currently available biosimilar on the market, Dr. Williams said.

While the limited number of respondents makes it difficult to draw concrete conclusions, Dr. Williams emphasized that the AAO supported the use of biosimilars. “We believe that with clinical experience ophthalmic biosimilars will become useful therapeutic agents,” he noted.

A version of this article first appeared on Medscape.com.

The latest guideline for perioperative management of antirheumatic medication in patients undergoing total hip (THA) and total knee arthroplasty (TKA) offers recommendations based on the latest evidence, but many of those recommendations are based on a low level of evidence, according to a speaker at the 2023 Rheumatology Winter Clinical Symposium.

Martin Bergman, MD, clinical professor of medicine at Drexel University, Philadelphia, said the development of the American College of Rheumatology/American Association of Hip and Knee Surgeons guideline was necessary because there was a lack of consensus on when to stop treatments prior to patients with rheumatologic disease undergoing THA and TKA, and when it was appropriate to restart those treatments.

“We all were having the same problem, and I think everybody recognized that just stopping medicines forever didn’t make sense, but maybe continuing medicines also didn’t make sense,” Dr. Bergman said.

While the 2017 ACR/AAHKS perioperative management guideline contained good recommendations, the “explosion” of new medications in rheumatology made it necessary to update the guideline with the latest data on new medications such as immunosuppressants.
 

2022 guideline recommendations

In the 2022 guideline, which covers disease-modifying treatments taken by patients with rheumatoid arthritis, spondyloarthritis, and psoriatic arthritis, the authors reaffirmed their recommendations to continue methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, and apremilast through total joint arthroplasty.

Where the 2022 guideline differs from the 2017 guideline is in which biologics are covered and under what circumstances they should be withheld and restarted around surgery. The 2022 guideline includes recommendations for abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, guselkumab, infliximab, ixekizumab, rituximab, secukinumab, tocilizumab, and ustekinumab. Each biologic has its own recommended stop and restart times based around the dosing interval and respective method of administration. Dr. Bergman said a general rule with biologics under the new guideline is that the timing of surgery should occur approximately 1 week after the first missed dose of the medication. The only biologic that does not follow this pattern is rituximab, where surgery should be planned for 1 month after the last missed dose.

Dr. Bergman noted that how the guidelines handle interval dosing with infliximab may present a problem. The guideline provides recommendations for patients receiving infliximab every 4 weeks, every 6 weeks, and every 8 weeks. However, Dr. Bergman said this can create a scenario where a patient receiving infliximab at a dose of 3 mg/kg every 8 weeks has surgery at 9 weeks, a patient receiving 5 mg/kg every 6 weeks has surgery at 7 weeks, and a patient receiving 10 mg/kg every 4 weeks has surgery at 5 weeks. “There is some intellectual problem with it,” he said.

Another change from the 2017 guideline is how long to wait for surgery after stopping Janus kinase inhibitors. While the 2017 guideline recommended withholding JAK inhibitors 7 days before surgery, the 2022 guideline lowered that waiting period to 3 days, Dr. Bergman explained.

Concerning use of steroids around THA and TKA surgery, “the days of stress steroid dosing are done,” Dr. Bergman said. “You don’t have to stress dose them. You just follow them, and you keep them on their steroid dose.”

The new guideline recommends restarting therapy once the wound is healed and there is no physical evidence of infection at approximately 2 weeks. “There’s no data to support this,” he said, and his concern is that patients who have stopped a tumor necrosis factor inhibitor may flare if they don’t restart their medication.

While the guideline also covered recommendations for systemic lupus erythematosus, they are “very similar” to the recommendations for inflammatory arthritis, Dr. Bergman noted. “If you have somebody who is not very sick, you stop the medications,” he said, “but try to stop anything else about a week before the surgery. If they’re sick, you basically have to keep them on their medications.”
 

Caveats in guideline

The recommendations in the 2022 guideline come with a number of caveats, Dr. Bergman noted. For instance, the authors acknowledged limitations in the guideline regarding providing recommendations for only THA and TKA, the “paucity of evidence” around direct infection risk resulting from medications in the perioperative period for THA and TKA, the nonseparation of biologics when assessing infection risk, and the use of dosing interval as a metric for stopping the drug without considering the drug’s half-life.

A “crucial caveat,” Dr. Bergman said, was that the guideline focused on infection risk based on a statement from a panel of patients prior to the development of the 2017 guideline, which “stated very clearly any risk of infection, while rare, was more significant to them than the possibility of postoperative flares, despite flares being reported in over 60% of patients after surgery.

“For the patients, the paramount question was infection, infection, infection, infection. That’s all they cared about, and that is the basis behind a lot of the decision-making here,” Dr. Bergman said.

Another caveat came from a communication Dr. Bergman received from one of the panel members. The panel member noted there were no conclusions or recommendations provided in the guideline for how to manage perioperative flares, such as restarting a corticosteroid or biologic agent. “There was a lot of discussion about what to do with steroids if patients flare, or what to do with [other] medications if they flare, and they just couldn’t come to a consensus,” Dr. Bergman said. “It’s just not discussed.”

Dr. Bergman said he is “somewhat critical” of the ACR/AAHKS guideline, but noted it is an “ambitious project” given the lack of evidence for the recommendations. “The alternative was stop the medications forever and having people really flare, or at least try to get some semblance of rationality behind what we’re going to do,” he said.
 

Response from attendees

Jack Cush, MD, a rheumatologist based in Dallas and executive editor of RheumNow.com, took issue with the new recommendations surrounding stopping infliximab. When giving a patient infliximab every 8 weeks at 3 mg/kg, “you’re giving [it] at the nadir of the drug,” he said.

Rather than drug half-life, “it’s about inflammation,” he emphasized. “Inflammation is dominant in causing infection. It drives risk more than anything. The worst thing you can do is wash someone out.

“If you’re going beyond 8 weeks on infliximab, you’re getting closer to washing them out,” he pointed out. “I think it’s a really bad idea.”

Allan Gibofsky, MD, JD, professor of medicine at Weill Cornell Medicine and codirector of the Clinic for Inflammatory Arthritis and Biologic Therapy at Hospital for Special Surgery, both in New York, explained that the guideline is not standard of care, which would be subject to malpractice if not implemented properly.

“When you have guidelines, you follow them unless there are clinical situations which would necessitate another approach to the patient,” he said. “Professional institutions and associations will never put forth rules, they will put forth guidelines so you have the opportunity to deviate from them when the appropriate clinical situation dictates.”

Dr. Bergman reported being a speaker and consultant for AbbVie, Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Novartis, Pfizer, and Regeneron; he holds stock in Johnson & Johnson and Merck.

The latest guideline for perioperative management of antirheumatic medication in patients undergoing total hip (THA) and total knee arthroplasty (TKA) offers recommendations based on the latest evidence, but many of those recommendations are based on a low level of evidence, according to a speaker at the 2023 Rheumatology Winter Clinical Symposium.

Martin Bergman, MD, clinical professor of medicine at Drexel University, Philadelphia, said the development of the American College of Rheumatology/American Association of Hip and Knee Surgeons guideline was necessary because there was a lack of consensus on when to stop treatments prior to patients with rheumatologic disease undergoing THA and TKA, and when it was appropriate to restart those treatments.

“We all were having the same problem, and I think everybody recognized that just stopping medicines forever didn’t make sense, but maybe continuing medicines also didn’t make sense,” Dr. Bergman said.

While the 2017 ACR/AAHKS perioperative management guideline contained good recommendations, the “explosion” of new medications in rheumatology made it necessary to update the guideline with the latest data on new medications such as immunosuppressants.
 

2022 guideline recommendations

In the 2022 guideline, which covers disease-modifying treatments taken by patients with rheumatoid arthritis, spondyloarthritis, and psoriatic arthritis, the authors reaffirmed their recommendations to continue methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, and apremilast through total joint arthroplasty.

Where the 2022 guideline differs from the 2017 guideline is in which biologics are covered and under what circumstances they should be withheld and restarted around surgery. The 2022 guideline includes recommendations for abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, guselkumab, infliximab, ixekizumab, rituximab, secukinumab, tocilizumab, and ustekinumab. Each biologic has its own recommended stop and restart times based around the dosing interval and respective method of administration. Dr. Bergman said a general rule with biologics under the new guideline is that the timing of surgery should occur approximately 1 week after the first missed dose of the medication. The only biologic that does not follow this pattern is rituximab, where surgery should be planned for 1 month after the last missed dose.

Dr. Bergman noted that how the guidelines handle interval dosing with infliximab may present a problem. The guideline provides recommendations for patients receiving infliximab every 4 weeks, every 6 weeks, and every 8 weeks. However, Dr. Bergman said this can create a scenario where a patient receiving infliximab at a dose of 3 mg/kg every 8 weeks has surgery at 9 weeks, a patient receiving 5 mg/kg every 6 weeks has surgery at 7 weeks, and a patient receiving 10 mg/kg every 4 weeks has surgery at 5 weeks. “There is some intellectual problem with it,” he said.

Another change from the 2017 guideline is how long to wait for surgery after stopping Janus kinase inhibitors. While the 2017 guideline recommended withholding JAK inhibitors 7 days before surgery, the 2022 guideline lowered that waiting period to 3 days, Dr. Bergman explained.

Concerning use of steroids around THA and TKA surgery, “the days of stress steroid dosing are done,” Dr. Bergman said. “You don’t have to stress dose them. You just follow them, and you keep them on their steroid dose.”

The new guideline recommends restarting therapy once the wound is healed and there is no physical evidence of infection at approximately 2 weeks. “There’s no data to support this,” he said, and his concern is that patients who have stopped a tumor necrosis factor inhibitor may flare if they don’t restart their medication.

While the guideline also covered recommendations for systemic lupus erythematosus, they are “very similar” to the recommendations for inflammatory arthritis, Dr. Bergman noted. “If you have somebody who is not very sick, you stop the medications,” he said, “but try to stop anything else about a week before the surgery. If they’re sick, you basically have to keep them on their medications.”
 

Caveats in guideline

The recommendations in the 2022 guideline come with a number of caveats, Dr. Bergman noted. For instance, the authors acknowledged limitations in the guideline regarding providing recommendations for only THA and TKA, the “paucity of evidence” around direct infection risk resulting from medications in the perioperative period for THA and TKA, the nonseparation of biologics when assessing infection risk, and the use of dosing interval as a metric for stopping the drug without considering the drug’s half-life.

A “crucial caveat,” Dr. Bergman said, was that the guideline focused on infection risk based on a statement from a panel of patients prior to the development of the 2017 guideline, which “stated very clearly any risk of infection, while rare, was more significant to them than the possibility of postoperative flares, despite flares being reported in over 60% of patients after surgery.

“For the patients, the paramount question was infection, infection, infection, infection. That’s all they cared about, and that is the basis behind a lot of the decision-making here,” Dr. Bergman said.

Another caveat came from a communication Dr. Bergman received from one of the panel members. The panel member noted there were no conclusions or recommendations provided in the guideline for how to manage perioperative flares, such as restarting a corticosteroid or biologic agent. “There was a lot of discussion about what to do with steroids if patients flare, or what to do with [other] medications if they flare, and they just couldn’t come to a consensus,” Dr. Bergman said. “It’s just not discussed.”

Dr. Bergman said he is “somewhat critical” of the ACR/AAHKS guideline, but noted it is an “ambitious project” given the lack of evidence for the recommendations. “The alternative was stop the medications forever and having people really flare, or at least try to get some semblance of rationality behind what we’re going to do,” he said.
 

Response from attendees

Jack Cush, MD, a rheumatologist based in Dallas and executive editor of RheumNow.com, took issue with the new recommendations surrounding stopping infliximab. When giving a patient infliximab every 8 weeks at 3 mg/kg, “you’re giving [it] at the nadir of the drug,” he said.

Rather than drug half-life, “it’s about inflammation,” he emphasized. “Inflammation is dominant in causing infection. It drives risk more than anything. The worst thing you can do is wash someone out.

“If you’re going beyond 8 weeks on infliximab, you’re getting closer to washing them out,” he pointed out. “I think it’s a really bad idea.”

Allan Gibofsky, MD, JD, professor of medicine at Weill Cornell Medicine and codirector of the Clinic for Inflammatory Arthritis and Biologic Therapy at Hospital for Special Surgery, both in New York, explained that the guideline is not standard of care, which would be subject to malpractice if not implemented properly.

“When you have guidelines, you follow them unless there are clinical situations which would necessitate another approach to the patient,” he said. “Professional institutions and associations will never put forth rules, they will put forth guidelines so you have the opportunity to deviate from them when the appropriate clinical situation dictates.”

Dr. Bergman reported being a speaker and consultant for AbbVie, Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Novartis, Pfizer, and Regeneron; he holds stock in Johnson & Johnson and Merck.

The latest guideline for perioperative management of antirheumatic medication in patients undergoing total hip (THA) and total knee arthroplasty (TKA) offers recommendations based on the latest evidence, but many of those recommendations are based on a low level of evidence, according to a speaker at the 2023 Rheumatology Winter Clinical Symposium.

Martin Bergman, MD, clinical professor of medicine at Drexel University, Philadelphia, said the development of the American College of Rheumatology/American Association of Hip and Knee Surgeons guideline was necessary because there was a lack of consensus on when to stop treatments prior to patients with rheumatologic disease undergoing THA and TKA, and when it was appropriate to restart those treatments.

“We all were having the same problem, and I think everybody recognized that just stopping medicines forever didn’t make sense, but maybe continuing medicines also didn’t make sense,” Dr. Bergman said.

While the 2017 ACR/AAHKS perioperative management guideline contained good recommendations, the “explosion” of new medications in rheumatology made it necessary to update the guideline with the latest data on new medications such as immunosuppressants.
 

2022 guideline recommendations

In the 2022 guideline, which covers disease-modifying treatments taken by patients with rheumatoid arthritis, spondyloarthritis, and psoriatic arthritis, the authors reaffirmed their recommendations to continue methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, and apremilast through total joint arthroplasty.

Where the 2022 guideline differs from the 2017 guideline is in which biologics are covered and under what circumstances they should be withheld and restarted around surgery. The 2022 guideline includes recommendations for abatacept, adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, guselkumab, infliximab, ixekizumab, rituximab, secukinumab, tocilizumab, and ustekinumab. Each biologic has its own recommended stop and restart times based around the dosing interval and respective method of administration. Dr. Bergman said a general rule with biologics under the new guideline is that the timing of surgery should occur approximately 1 week after the first missed dose of the medication. The only biologic that does not follow this pattern is rituximab, where surgery should be planned for 1 month after the last missed dose.

Dr. Bergman noted that how the guidelines handle interval dosing with infliximab may present a problem. The guideline provides recommendations for patients receiving infliximab every 4 weeks, every 6 weeks, and every 8 weeks. However, Dr. Bergman said this can create a scenario where a patient receiving infliximab at a dose of 3 mg/kg every 8 weeks has surgery at 9 weeks, a patient receiving 5 mg/kg every 6 weeks has surgery at 7 weeks, and a patient receiving 10 mg/kg every 4 weeks has surgery at 5 weeks. “There is some intellectual problem with it,” he said.

Another change from the 2017 guideline is how long to wait for surgery after stopping Janus kinase inhibitors. While the 2017 guideline recommended withholding JAK inhibitors 7 days before surgery, the 2022 guideline lowered that waiting period to 3 days, Dr. Bergman explained.

Concerning use of steroids around THA and TKA surgery, “the days of stress steroid dosing are done,” Dr. Bergman said. “You don’t have to stress dose them. You just follow them, and you keep them on their steroid dose.”

The new guideline recommends restarting therapy once the wound is healed and there is no physical evidence of infection at approximately 2 weeks. “There’s no data to support this,” he said, and his concern is that patients who have stopped a tumor necrosis factor inhibitor may flare if they don’t restart their medication.

While the guideline also covered recommendations for systemic lupus erythematosus, they are “very similar” to the recommendations for inflammatory arthritis, Dr. Bergman noted. “If you have somebody who is not very sick, you stop the medications,” he said, “but try to stop anything else about a week before the surgery. If they’re sick, you basically have to keep them on their medications.”
 

Caveats in guideline

The recommendations in the 2022 guideline come with a number of caveats, Dr. Bergman noted. For instance, the authors acknowledged limitations in the guideline regarding providing recommendations for only THA and TKA, the “paucity of evidence” around direct infection risk resulting from medications in the perioperative period for THA and TKA, the nonseparation of biologics when assessing infection risk, and the use of dosing interval as a metric for stopping the drug without considering the drug’s half-life.

A “crucial caveat,” Dr. Bergman said, was that the guideline focused on infection risk based on a statement from a panel of patients prior to the development of the 2017 guideline, which “stated very clearly any risk of infection, while rare, was more significant to them than the possibility of postoperative flares, despite flares being reported in over 60% of patients after surgery.

“For the patients, the paramount question was infection, infection, infection, infection. That’s all they cared about, and that is the basis behind a lot of the decision-making here,” Dr. Bergman said.

Another caveat came from a communication Dr. Bergman received from one of the panel members. The panel member noted there were no conclusions or recommendations provided in the guideline for how to manage perioperative flares, such as restarting a corticosteroid or biologic agent. “There was a lot of discussion about what to do with steroids if patients flare, or what to do with [other] medications if they flare, and they just couldn’t come to a consensus,” Dr. Bergman said. “It’s just not discussed.”

Dr. Bergman said he is “somewhat critical” of the ACR/AAHKS guideline, but noted it is an “ambitious project” given the lack of evidence for the recommendations. “The alternative was stop the medications forever and having people really flare, or at least try to get some semblance of rationality behind what we’re going to do,” he said.
 

Response from attendees

Jack Cush, MD, a rheumatologist based in Dallas and executive editor of RheumNow.com, took issue with the new recommendations surrounding stopping infliximab. When giving a patient infliximab every 8 weeks at 3 mg/kg, “you’re giving [it] at the nadir of the drug,” he said.

Rather than drug half-life, “it’s about inflammation,” he emphasized. “Inflammation is dominant in causing infection. It drives risk more than anything. The worst thing you can do is wash someone out.

“If you’re going beyond 8 weeks on infliximab, you’re getting closer to washing them out,” he pointed out. “I think it’s a really bad idea.”

Allan Gibofsky, MD, JD, professor of medicine at Weill Cornell Medicine and codirector of the Clinic for Inflammatory Arthritis and Biologic Therapy at Hospital for Special Surgery, both in New York, explained that the guideline is not standard of care, which would be subject to malpractice if not implemented properly.

“When you have guidelines, you follow them unless there are clinical situations which would necessitate another approach to the patient,” he said. “Professional institutions and associations will never put forth rules, they will put forth guidelines so you have the opportunity to deviate from them when the appropriate clinical situation dictates.”

Dr. Bergman reported being a speaker and consultant for AbbVie, Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Novartis, Pfizer, and Regeneron; he holds stock in Johnson & Johnson and Merck.

IgG4 fights viruses and bacteria. However, sometimes it targets the body itself. “This then leads to inflammation, the healing of which the body is unable to keep under control,” explained Ulf Müller-Ladner, MD, PhD, chairperson of the German Society of Internal Medicine.

At the DGIM annual press conference, Dr. Müller-Ladner, who is also director of the department of rheumatology and clinical immunology at the Kerckhoff Clinic in Bad Nauheim, Germany, explained how IgG4 inflammation is triggered throughout the body and what therapeutic options are available.
 

Many manifestations

IgG4-associated inflammation can affect one or more organs or the surrounding connective tissue and cause fibrosis. As a result of fibrosis, the organ gradually loses function and is eventually transformed completely into scarred connective tissue.

“In the case of IgG4-associated inflammation, these fibroses have a histological structure, but extracting a sample is not possible from every affected organ,” said Dr. Müller-Ladner. Liver, bile ducts, blood vessels, skin, eyes, or even the central nervous system – practically every organ system can be affected by these inflammatory reactions.

IgG4-associated diseases have likely been around for some time, but it is only in the past 10 years that awareness has grown that, despite various manifestations, “they are all one and the same disease,” said Dr. Müller-Ladner.

IgG4-associated chronic, inflammatory, fibrosing diseases were only classified together as a single entity in the past few years. In terms of pathophysiology, B lymphocytes, IgG4-positive plasma cells, follicular T-helper cells, cytotoxic CD4-positive T cells, and macrophages work together and trigger an inflammatory reaction, which then encourages fibroblasts to overproduce connective tissue.
 

Beware inexplicable inflammation

It is estimated that 1 in 100,000 people suffer from the disease, but the number of incorrectly categorized patients may be significantly higher.

The diagnostic challenge lies in the fact that IgG4-associated inflammation occurs in almost every organ. It can cause different symptoms, depending on the organ affected.

Dr. Müller-Ladner provided the following take-home message: “Every inexplicable inflammation event and every organ dysfunction, especially if associated with an increase in connective tissue, could be an IgG4-associated disease. Keeping this in mind is the key to recovery.”

With most people, the inflammation persists for many years before any symptoms of the disease develop. Highly acute courses of progression are also possible.

Classic symptoms, such as fever, are not so characteristic of the latent inflammatory reaction, and according to classification criteria published by specialist rheumatology societies, they are an exclusion criterion. This is true with respect to the differential diagnosis for vasculitis, which also occurs throughout the body.
 

Histology is key

Blood levels of IgG4 and imaging are not always enough to confirm the diagnosis. In such cases, the histology is often a crucial factor in making a definitive diagnosis. Dominant organs in IgG4-associated diseases are the pancreas, the liver, the gallbladder, the intestines, the retroperitoneum, large blood vessels, the kidneys, the heart, the brain, saliva, tear ducts, as well all of the body’s connective tissue.

The kidneys play host to inflammation in the connective tissue and space-occupying masses in particular. “If the pancreas is affected, the signs can vary from diffuse swelling to the onset of diabetes mellitus. In contrast, if the aorta is affected, then the inflammation is characterized through a thickening of the vessel walls, aneurysms, and the corresponding circulation disorders,” said Dr. Müller-Ladner.

Because of the long period before the diagnosis is made, more than 50% of patients exhibit irreversible organ damage at the time of diagnosis, he added.
 

Glucocorticoids and immunosuppressants

Despite therapeutic intervention, the disease can have a fatal outcome, even if the patient is young, said Dr. Müller-Ladner. Glucocorticoids are the current therapy of choice. The dose is more than 0.5 mg of prednisolone equivalent per kg of body weight. “This usually leads to a rapid improvement in the inflammation. Subsequently, every organ is thoroughly diagnosed to assess the severity of the disease and to plan further treatment steps.”

In the long term, proven immunosuppressants, such as azathioprine, mycophenolate, leflunomide, and methotrexate, can be used, just as for many other chronic inflammatory diseases. Cyclophosphamide or cyclosporine is used more rarely, owing to their side effect profiles.

Because of the B-cell dominance, B-cell–depleting therapy with rituximab is currently a highly effective therapeutic option but one that must be applied for, because such use is off label. “If the body responds well to the medication, organ function often recovers,” said Dr. Müller-Ladner.

This article was translated from the Medscape German edition. A version appeared on Medscape.com.

IgG4 fights viruses and bacteria. However, sometimes it targets the body itself. “This then leads to inflammation, the healing of which the body is unable to keep under control,” explained Ulf Müller-Ladner, MD, PhD, chairperson of the German Society of Internal Medicine.

At the DGIM annual press conference, Dr. Müller-Ladner, who is also director of the department of rheumatology and clinical immunology at the Kerckhoff Clinic in Bad Nauheim, Germany, explained how IgG4 inflammation is triggered throughout the body and what therapeutic options are available.
 

Many manifestations

IgG4-associated inflammation can affect one or more organs or the surrounding connective tissue and cause fibrosis. As a result of fibrosis, the organ gradually loses function and is eventually transformed completely into scarred connective tissue.

“In the case of IgG4-associated inflammation, these fibroses have a histological structure, but extracting a sample is not possible from every affected organ,” said Dr. Müller-Ladner. Liver, bile ducts, blood vessels, skin, eyes, or even the central nervous system – practically every organ system can be affected by these inflammatory reactions.

IgG4-associated diseases have likely been around for some time, but it is only in the past 10 years that awareness has grown that, despite various manifestations, “they are all one and the same disease,” said Dr. Müller-Ladner.

IgG4-associated chronic, inflammatory, fibrosing diseases were only classified together as a single entity in the past few years. In terms of pathophysiology, B lymphocytes, IgG4-positive plasma cells, follicular T-helper cells, cytotoxic CD4-positive T cells, and macrophages work together and trigger an inflammatory reaction, which then encourages fibroblasts to overproduce connective tissue.
 

Beware inexplicable inflammation

It is estimated that 1 in 100,000 people suffer from the disease, but the number of incorrectly categorized patients may be significantly higher.

The diagnostic challenge lies in the fact that IgG4-associated inflammation occurs in almost every organ. It can cause different symptoms, depending on the organ affected.

Dr. Müller-Ladner provided the following take-home message: “Every inexplicable inflammation event and every organ dysfunction, especially if associated with an increase in connective tissue, could be an IgG4-associated disease. Keeping this in mind is the key to recovery.”

With most people, the inflammation persists for many years before any symptoms of the disease develop. Highly acute courses of progression are also possible.

Classic symptoms, such as fever, are not so characteristic of the latent inflammatory reaction, and according to classification criteria published by specialist rheumatology societies, they are an exclusion criterion. This is true with respect to the differential diagnosis for vasculitis, which also occurs throughout the body.
 

Histology is key

Blood levels of IgG4 and imaging are not always enough to confirm the diagnosis. In such cases, the histology is often a crucial factor in making a definitive diagnosis. Dominant organs in IgG4-associated diseases are the pancreas, the liver, the gallbladder, the intestines, the retroperitoneum, large blood vessels, the kidneys, the heart, the brain, saliva, tear ducts, as well all of the body’s connective tissue.

The kidneys play host to inflammation in the connective tissue and space-occupying masses in particular. “If the pancreas is affected, the signs can vary from diffuse swelling to the onset of diabetes mellitus. In contrast, if the aorta is affected, then the inflammation is characterized through a thickening of the vessel walls, aneurysms, and the corresponding circulation disorders,” said Dr. Müller-Ladner.

Because of the long period before the diagnosis is made, more than 50% of patients exhibit irreversible organ damage at the time of diagnosis, he added.
 

Glucocorticoids and immunosuppressants

Despite therapeutic intervention, the disease can have a fatal outcome, even if the patient is young, said Dr. Müller-Ladner. Glucocorticoids are the current therapy of choice. The dose is more than 0.5 mg of prednisolone equivalent per kg of body weight. “This usually leads to a rapid improvement in the inflammation. Subsequently, every organ is thoroughly diagnosed to assess the severity of the disease and to plan further treatment steps.”

In the long term, proven immunosuppressants, such as azathioprine, mycophenolate, leflunomide, and methotrexate, can be used, just as for many other chronic inflammatory diseases. Cyclophosphamide or cyclosporine is used more rarely, owing to their side effect profiles.

Because of the B-cell dominance, B-cell–depleting therapy with rituximab is currently a highly effective therapeutic option but one that must be applied for, because such use is off label. “If the body responds well to the medication, organ function often recovers,” said Dr. Müller-Ladner.

This article was translated from the Medscape German edition. A version appeared on Medscape.com.

IgG4 fights viruses and bacteria. However, sometimes it targets the body itself. “This then leads to inflammation, the healing of which the body is unable to keep under control,” explained Ulf Müller-Ladner, MD, PhD, chairperson of the German Society of Internal Medicine.

At the DGIM annual press conference, Dr. Müller-Ladner, who is also director of the department of rheumatology and clinical immunology at the Kerckhoff Clinic in Bad Nauheim, Germany, explained how IgG4 inflammation is triggered throughout the body and what therapeutic options are available.
 

Many manifestations

IgG4-associated inflammation can affect one or more organs or the surrounding connective tissue and cause fibrosis. As a result of fibrosis, the organ gradually loses function and is eventually transformed completely into scarred connective tissue.

“In the case of IgG4-associated inflammation, these fibroses have a histological structure, but extracting a sample is not possible from every affected organ,” said Dr. Müller-Ladner. Liver, bile ducts, blood vessels, skin, eyes, or even the central nervous system – practically every organ system can be affected by these inflammatory reactions.

IgG4-associated diseases have likely been around for some time, but it is only in the past 10 years that awareness has grown that, despite various manifestations, “they are all one and the same disease,” said Dr. Müller-Ladner.

IgG4-associated chronic, inflammatory, fibrosing diseases were only classified together as a single entity in the past few years. In terms of pathophysiology, B lymphocytes, IgG4-positive plasma cells, follicular T-helper cells, cytotoxic CD4-positive T cells, and macrophages work together and trigger an inflammatory reaction, which then encourages fibroblasts to overproduce connective tissue.
 

Beware inexplicable inflammation

It is estimated that 1 in 100,000 people suffer from the disease, but the number of incorrectly categorized patients may be significantly higher.

The diagnostic challenge lies in the fact that IgG4-associated inflammation occurs in almost every organ. It can cause different symptoms, depending on the organ affected.

Dr. Müller-Ladner provided the following take-home message: “Every inexplicable inflammation event and every organ dysfunction, especially if associated with an increase in connective tissue, could be an IgG4-associated disease. Keeping this in mind is the key to recovery.”

With most people, the inflammation persists for many years before any symptoms of the disease develop. Highly acute courses of progression are also possible.

Classic symptoms, such as fever, are not so characteristic of the latent inflammatory reaction, and according to classification criteria published by specialist rheumatology societies, they are an exclusion criterion. This is true with respect to the differential diagnosis for vasculitis, which also occurs throughout the body.
 

Histology is key

Blood levels of IgG4 and imaging are not always enough to confirm the diagnosis. In such cases, the histology is often a crucial factor in making a definitive diagnosis. Dominant organs in IgG4-associated diseases are the pancreas, the liver, the gallbladder, the intestines, the retroperitoneum, large blood vessels, the kidneys, the heart, the brain, saliva, tear ducts, as well all of the body’s connective tissue.

The kidneys play host to inflammation in the connective tissue and space-occupying masses in particular. “If the pancreas is affected, the signs can vary from diffuse swelling to the onset of diabetes mellitus. In contrast, if the aorta is affected, then the inflammation is characterized through a thickening of the vessel walls, aneurysms, and the corresponding circulation disorders,” said Dr. Müller-Ladner.

Because of the long period before the diagnosis is made, more than 50% of patients exhibit irreversible organ damage at the time of diagnosis, he added.
 

Glucocorticoids and immunosuppressants

Despite therapeutic intervention, the disease can have a fatal outcome, even if the patient is young, said Dr. Müller-Ladner. Glucocorticoids are the current therapy of choice. The dose is more than 0.5 mg of prednisolone equivalent per kg of body weight. “This usually leads to a rapid improvement in the inflammation. Subsequently, every organ is thoroughly diagnosed to assess the severity of the disease and to plan further treatment steps.”

In the long term, proven immunosuppressants, such as azathioprine, mycophenolate, leflunomide, and methotrexate, can be used, just as for many other chronic inflammatory diseases. Cyclophosphamide or cyclosporine is used more rarely, owing to their side effect profiles.

Because of the B-cell dominance, B-cell–depleting therapy with rituximab is currently a highly effective therapeutic option but one that must be applied for, because such use is off label. “If the body responds well to the medication, organ function often recovers,” said Dr. Müller-Ladner.

This article was translated from the Medscape German edition. A version appeared on Medscape.com.

Follow-up radiographs after an initial baseline reading in patients with rheumatoid arthritis or psoriatic arthritis may still show radiographic progression despite treatment with current therapies, but it’s unclear if they will affect treatment decisions between patients and doctors that may take place regardless of the radiographic information, according to arguments made for and against their usefulness in a point-counterpoint session at the 2023 Rheumatology Winter Clinical Symposium.

Alvin Wells, MD, PhD, director of the department of rheumatology at Advocate Aurora Health in Franklin, Wisc., said that x-rays “reflect the history of joint pathology” and can get worse over time, correlating with disease activity and severity.

BSIP/UIG/GettyImages

While RA does not yet have the “holy grail” of complete or true remission, Dr. Wells argued, the combination of clinical remission, laboratory remission, and imaging remission gets patients with RA close to the ideal when measured over time. “You need to continue to monitor these patients as you follow them along,” he said.

The BARFOT study, which evaluated 1,938 patients with early RA in two cohorts during 1992-1999 and again between 2000 and 2006, showed that more active treatments in the 2000s did not result in improvements in Health Assessment Questionnaire (HAQ) and pain scores, compared with patients treated in the 1990s. “You can see in some of those patients those scores do increase, and that even despite aggressive therapies that we had in 2006, you can still see some of those patients still have progression of the disease,” Dr. Wells explained. “How did they know? Because they looked.”

He also cited a study from researchers at the Mayo Clinic who examined 586 patients with RA that showed a higher prevalence of functional disability in patients with RA who also had radiographic changes, compared with patients without RA. “Radiographic changes correlate with disease severity and functional disability as well,” Dr. Wells said.

Just as prostate-specific antigen levels are used in prostate cancer screening and hemoglobin A1c is measured in diabetes management, radiographs should be used to track progression of disease in RA and PsA, Dr. Wells argued. “[I]f you don’t know, you can’t treat,” he said.

Some patients near remission may have radiographic progression even though disease activity measurements such as C-reactive protein (CRP) values do not show presence of active disease. In a study analyzing 1,184 patients with RA in the ASPIRE, ERA, Leflunomide, PREMIER and TEMPO trials, swollen joint count (SJC) was a better predictor of radiographic progression than CRP in patients near remission.

“[E]ven where you don’t see smoke, there still could be fire,” Dr. Wells said. “Some of these patients still progress and these are outliers, and the way they saw that [was] because they followed those patients along. If you don’t look, you don’t know.”

Radiographic progression can also be seen among nonswollen joints in patients with RA and PsA. In a study of 1,207 joints in 55 patients with RA and 352 joints in 18 patients with PsA, researchers in Austria found tenderness in nonswollen joints was associated with radiographic progression.

Despite having effective treatments in RA and PsA, “none of our therapies show that they’re able to prevent progression,” Dr. Wells said.

When it comes to hitting the treatment target in RA, some rheumatologists may think they can accomplish it without use of repeated radiographs. “I have a different perspective on that – that you really do indeed need to do the x-rays today and follow those x-rays along, especially if it’s going to change your treatment paradigm and what your treatment decision would be for the patient,” he said.
 

Counterpoint: Repeat radiographs aren’t helpful

Almost all rheumatologists would likely order an initial radiograph for their patients with RA or PsA, Roy M. Fleischmann, MD, clinical professor of medicine at the University of Texas and codirector of the Metroplex Clinical Research Center, both in Dallas, said in his presentation.

“If you see erosions when you start, chances are you’re going to be much more aggressive,” Dr. Fleischmann said. “So it is justification for early, more aggressive treatment of disease.”

In recent decades, radiographic progression in RA has decreased as more effective antirheumatic treatments have come into use, Dr. Fleischmann argued.

“We had x-ray progression in virtually everybody, and it was consistent no matter what we treated with, which was gold or penicillamine or any of the NSAIDs or sulfasalazine,” he said. “With methotrexate ... about 60% of patients actually have no x-ray progression, and that was a major change, and that’s one of the reasons why methotrexate has become the keystone of therapy. But even with methotrexate, [we] still had many patients who progressed.”

After the introduction of tumor necrosis factor inhibitors and other mechanisms in the late 1990s, “all of a sudden, you don’t see x-ray progression – mean x-ray progression – in a group of patients,” he noted.

Many rheumatologists now use a treat-to-target strategy, and if the patient achieves true clinical remission or sustained very low disease activity as measured by Boolean remission, Simple Disease Activity Index, or Clinical Disease Activity Index, they have “very little chance of radiographic progression and functional decline,” he said.

“If a patient doesn’t achieve remission or very low disease activity, obtaining a radiograph doesn’t change what you do because the patient’s not where they want to be, where you want them to be; you’re going to make a change anyway,” Dr. Fleischmann explained. “The radiograph isn’t going to help you do that.”

If a patient is in sustained remission but a radiograph is ordered and shows disease progression, he questioned what the rheumatologist would do in that situation.

“Now the patient’s in, let’s say, a Boolean remission. They have no tender joints. They have no swollen joints ... their pain assessment is zero, their CRP is zero, and they do have some x-ray progression. Where are you going to change?” Dr. Fleischmann asked. “There’s no data that anything else would work. I don’t know what you would do. So, in conclusion, I would say you really don’t need to repeat an x-ray.”
 

AI reading x-rays?

Commenting on the point-counterpoint session, Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego, and director of RWCS, asked Dr. Fleischmann and Dr. Wells how they address the issue of how many radiologists seem to be unfamiliar with reading hand radiographs and RA progression.

Dr. Fleischmann said he was trained in how to read hand radiographs in medical school, but that training no longer appears to be occurring. “If you have a good bone radiologist, of which there are not a lot, you’re great. But if you don’t have a really good bone radiologist, it’s difficult,” he said.

Dr. Kavanaugh alluded to the advancement of artificial intelligence (AI) in radiology and posed the question of how both rheumatologists felt about AI reading and interpreting their radiographs. “If you could reliably submit x-rays and they would say what the Sharp score was and where the differences were, would that change anything?” he asked.

“I think having artificial intelligence read the x-ray or an MRI is really, really good. It’ll be better than the radiologists,” Dr. Fleischmann responded. “But I don’t think that you really need to repeat the x-ray. I mean, I really don’t think you need to repeat it. You need to treat the patient.”

Dr. Wells reported having financial relationships with numerous pharmaceutical companies. Dr. Fleischmann reported no relevant financial relationships.

Follow-up radiographs after an initial baseline reading in patients with rheumatoid arthritis or psoriatic arthritis may still show radiographic progression despite treatment with current therapies, but it’s unclear if they will affect treatment decisions between patients and doctors that may take place regardless of the radiographic information, according to arguments made for and against their usefulness in a point-counterpoint session at the 2023 Rheumatology Winter Clinical Symposium.

Alvin Wells, MD, PhD, director of the department of rheumatology at Advocate Aurora Health in Franklin, Wisc., said that x-rays “reflect the history of joint pathology” and can get worse over time, correlating with disease activity and severity.

BSIP/UIG/GettyImages

While RA does not yet have the “holy grail” of complete or true remission, Dr. Wells argued, the combination of clinical remission, laboratory remission, and imaging remission gets patients with RA close to the ideal when measured over time. “You need to continue to monitor these patients as you follow them along,” he said.

The BARFOT study, which evaluated 1,938 patients with early RA in two cohorts during 1992-1999 and again between 2000 and 2006, showed that more active treatments in the 2000s did not result in improvements in Health Assessment Questionnaire (HAQ) and pain scores, compared with patients treated in the 1990s. “You can see in some of those patients those scores do increase, and that even despite aggressive therapies that we had in 2006, you can still see some of those patients still have progression of the disease,” Dr. Wells explained. “How did they know? Because they looked.”

He also cited a study from researchers at the Mayo Clinic who examined 586 patients with RA that showed a higher prevalence of functional disability in patients with RA who also had radiographic changes, compared with patients without RA. “Radiographic changes correlate with disease severity and functional disability as well,” Dr. Wells said.

Just as prostate-specific antigen levels are used in prostate cancer screening and hemoglobin A1c is measured in diabetes management, radiographs should be used to track progression of disease in RA and PsA, Dr. Wells argued. “[I]f you don’t know, you can’t treat,” he said.

Some patients near remission may have radiographic progression even though disease activity measurements such as C-reactive protein (CRP) values do not show presence of active disease. In a study analyzing 1,184 patients with RA in the ASPIRE, ERA, Leflunomide, PREMIER and TEMPO trials, swollen joint count (SJC) was a better predictor of radiographic progression than CRP in patients near remission.

“[E]ven where you don’t see smoke, there still could be fire,” Dr. Wells said. “Some of these patients still progress and these are outliers, and the way they saw that [was] because they followed those patients along. If you don’t look, you don’t know.”

Radiographic progression can also be seen among nonswollen joints in patients with RA and PsA. In a study of 1,207 joints in 55 patients with RA and 352 joints in 18 patients with PsA, researchers in Austria found tenderness in nonswollen joints was associated with radiographic progression.

Despite having effective treatments in RA and PsA, “none of our therapies show that they’re able to prevent progression,” Dr. Wells said.

When it comes to hitting the treatment target in RA, some rheumatologists may think they can accomplish it without use of repeated radiographs. “I have a different perspective on that – that you really do indeed need to do the x-rays today and follow those x-rays along, especially if it’s going to change your treatment paradigm and what your treatment decision would be for the patient,” he said.
 

Counterpoint: Repeat radiographs aren’t helpful

Almost all rheumatologists would likely order an initial radiograph for their patients with RA or PsA, Roy M. Fleischmann, MD, clinical professor of medicine at the University of Texas and codirector of the Metroplex Clinical Research Center, both in Dallas, said in his presentation.

“If you see erosions when you start, chances are you’re going to be much more aggressive,” Dr. Fleischmann said. “So it is justification for early, more aggressive treatment of disease.”

In recent decades, radiographic progression in RA has decreased as more effective antirheumatic treatments have come into use, Dr. Fleischmann argued.

“We had x-ray progression in virtually everybody, and it was consistent no matter what we treated with, which was gold or penicillamine or any of the NSAIDs or sulfasalazine,” he said. “With methotrexate ... about 60% of patients actually have no x-ray progression, and that was a major change, and that’s one of the reasons why methotrexate has become the keystone of therapy. But even with methotrexate, [we] still had many patients who progressed.”

After the introduction of tumor necrosis factor inhibitors and other mechanisms in the late 1990s, “all of a sudden, you don’t see x-ray progression – mean x-ray progression – in a group of patients,” he noted.

Many rheumatologists now use a treat-to-target strategy, and if the patient achieves true clinical remission or sustained very low disease activity as measured by Boolean remission, Simple Disease Activity Index, or Clinical Disease Activity Index, they have “very little chance of radiographic progression and functional decline,” he said.

“If a patient doesn’t achieve remission or very low disease activity, obtaining a radiograph doesn’t change what you do because the patient’s not where they want to be, where you want them to be; you’re going to make a change anyway,” Dr. Fleischmann explained. “The radiograph isn’t going to help you do that.”

If a patient is in sustained remission but a radiograph is ordered and shows disease progression, he questioned what the rheumatologist would do in that situation.

“Now the patient’s in, let’s say, a Boolean remission. They have no tender joints. They have no swollen joints ... their pain assessment is zero, their CRP is zero, and they do have some x-ray progression. Where are you going to change?” Dr. Fleischmann asked. “There’s no data that anything else would work. I don’t know what you would do. So, in conclusion, I would say you really don’t need to repeat an x-ray.”
 

AI reading x-rays?

Commenting on the point-counterpoint session, Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego, and director of RWCS, asked Dr. Fleischmann and Dr. Wells how they address the issue of how many radiologists seem to be unfamiliar with reading hand radiographs and RA progression.

Dr. Fleischmann said he was trained in how to read hand radiographs in medical school, but that training no longer appears to be occurring. “If you have a good bone radiologist, of which there are not a lot, you’re great. But if you don’t have a really good bone radiologist, it’s difficult,” he said.

Dr. Kavanaugh alluded to the advancement of artificial intelligence (AI) in radiology and posed the question of how both rheumatologists felt about AI reading and interpreting their radiographs. “If you could reliably submit x-rays and they would say what the Sharp score was and where the differences were, would that change anything?” he asked.

“I think having artificial intelligence read the x-ray or an MRI is really, really good. It’ll be better than the radiologists,” Dr. Fleischmann responded. “But I don’t think that you really need to repeat the x-ray. I mean, I really don’t think you need to repeat it. You need to treat the patient.”

Dr. Wells reported having financial relationships with numerous pharmaceutical companies. Dr. Fleischmann reported no relevant financial relationships.

Follow-up radiographs after an initial baseline reading in patients with rheumatoid arthritis or psoriatic arthritis may still show radiographic progression despite treatment with current therapies, but it’s unclear if they will affect treatment decisions between patients and doctors that may take place regardless of the radiographic information, according to arguments made for and against their usefulness in a point-counterpoint session at the 2023 Rheumatology Winter Clinical Symposium.

Alvin Wells, MD, PhD, director of the department of rheumatology at Advocate Aurora Health in Franklin, Wisc., said that x-rays “reflect the history of joint pathology” and can get worse over time, correlating with disease activity and severity.

BSIP/UIG/GettyImages

While RA does not yet have the “holy grail” of complete or true remission, Dr. Wells argued, the combination of clinical remission, laboratory remission, and imaging remission gets patients with RA close to the ideal when measured over time. “You need to continue to monitor these patients as you follow them along,” he said.

The BARFOT study, which evaluated 1,938 patients with early RA in two cohorts during 1992-1999 and again between 2000 and 2006, showed that more active treatments in the 2000s did not result in improvements in Health Assessment Questionnaire (HAQ) and pain scores, compared with patients treated in the 1990s. “You can see in some of those patients those scores do increase, and that even despite aggressive therapies that we had in 2006, you can still see some of those patients still have progression of the disease,” Dr. Wells explained. “How did they know? Because they looked.”

He also cited a study from researchers at the Mayo Clinic who examined 586 patients with RA that showed a higher prevalence of functional disability in patients with RA who also had radiographic changes, compared with patients without RA. “Radiographic changes correlate with disease severity and functional disability as well,” Dr. Wells said.

Just as prostate-specific antigen levels are used in prostate cancer screening and hemoglobin A1c is measured in diabetes management, radiographs should be used to track progression of disease in RA and PsA, Dr. Wells argued. “[I]f you don’t know, you can’t treat,” he said.

Some patients near remission may have radiographic progression even though disease activity measurements such as C-reactive protein (CRP) values do not show presence of active disease. In a study analyzing 1,184 patients with RA in the ASPIRE, ERA, Leflunomide, PREMIER and TEMPO trials, swollen joint count (SJC) was a better predictor of radiographic progression than CRP in patients near remission.

“[E]ven where you don’t see smoke, there still could be fire,” Dr. Wells said. “Some of these patients still progress and these are outliers, and the way they saw that [was] because they followed those patients along. If you don’t look, you don’t know.”

Radiographic progression can also be seen among nonswollen joints in patients with RA and PsA. In a study of 1,207 joints in 55 patients with RA and 352 joints in 18 patients with PsA, researchers in Austria found tenderness in nonswollen joints was associated with radiographic progression.

Despite having effective treatments in RA and PsA, “none of our therapies show that they’re able to prevent progression,” Dr. Wells said.

When it comes to hitting the treatment target in RA, some rheumatologists may think they can accomplish it without use of repeated radiographs. “I have a different perspective on that – that you really do indeed need to do the x-rays today and follow those x-rays along, especially if it’s going to change your treatment paradigm and what your treatment decision would be for the patient,” he said.
 

Counterpoint: Repeat radiographs aren’t helpful

Almost all rheumatologists would likely order an initial radiograph for their patients with RA or PsA, Roy M. Fleischmann, MD, clinical professor of medicine at the University of Texas and codirector of the Metroplex Clinical Research Center, both in Dallas, said in his presentation.

“If you see erosions when you start, chances are you’re going to be much more aggressive,” Dr. Fleischmann said. “So it is justification for early, more aggressive treatment of disease.”

In recent decades, radiographic progression in RA has decreased as more effective antirheumatic treatments have come into use, Dr. Fleischmann argued.

“We had x-ray progression in virtually everybody, and it was consistent no matter what we treated with, which was gold or penicillamine or any of the NSAIDs or sulfasalazine,” he said. “With methotrexate ... about 60% of patients actually have no x-ray progression, and that was a major change, and that’s one of the reasons why methotrexate has become the keystone of therapy. But even with methotrexate, [we] still had many patients who progressed.”

After the introduction of tumor necrosis factor inhibitors and other mechanisms in the late 1990s, “all of a sudden, you don’t see x-ray progression – mean x-ray progression – in a group of patients,” he noted.

Many rheumatologists now use a treat-to-target strategy, and if the patient achieves true clinical remission or sustained very low disease activity as measured by Boolean remission, Simple Disease Activity Index, or Clinical Disease Activity Index, they have “very little chance of radiographic progression and functional decline,” he said.

“If a patient doesn’t achieve remission or very low disease activity, obtaining a radiograph doesn’t change what you do because the patient’s not where they want to be, where you want them to be; you’re going to make a change anyway,” Dr. Fleischmann explained. “The radiograph isn’t going to help you do that.”

If a patient is in sustained remission but a radiograph is ordered and shows disease progression, he questioned what the rheumatologist would do in that situation.

“Now the patient’s in, let’s say, a Boolean remission. They have no tender joints. They have no swollen joints ... their pain assessment is zero, their CRP is zero, and they do have some x-ray progression. Where are you going to change?” Dr. Fleischmann asked. “There’s no data that anything else would work. I don’t know what you would do. So, in conclusion, I would say you really don’t need to repeat an x-ray.”
 

AI reading x-rays?

Commenting on the point-counterpoint session, Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego, and director of RWCS, asked Dr. Fleischmann and Dr. Wells how they address the issue of how many radiologists seem to be unfamiliar with reading hand radiographs and RA progression.

Dr. Fleischmann said he was trained in how to read hand radiographs in medical school, but that training no longer appears to be occurring. “If you have a good bone radiologist, of which there are not a lot, you’re great. But if you don’t have a really good bone radiologist, it’s difficult,” he said.

Dr. Kavanaugh alluded to the advancement of artificial intelligence (AI) in radiology and posed the question of how both rheumatologists felt about AI reading and interpreting their radiographs. “If you could reliably submit x-rays and they would say what the Sharp score was and where the differences were, would that change anything?” he asked.

“I think having artificial intelligence read the x-ray or an MRI is really, really good. It’ll be better than the radiologists,” Dr. Fleischmann responded. “But I don’t think that you really need to repeat the x-ray. I mean, I really don’t think you need to repeat it. You need to treat the patient.”

Dr. Wells reported having financial relationships with numerous pharmaceutical companies. Dr. Fleischmann reported no relevant financial relationships.