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For MD-IQ on Family Practice News, but a regular topic for Rheumatology News
FDA warning letters target OTC cannabidiol product claims for pain relief
The Food and Drug Administration has warned two manufacturers about illegal marketing of drugs containing cannabidiol (CBD) for over-the-counter use without an approved new drug application, for using substandard manufacturing processes, and for failure to comply with current good manufacturing practices. These warnings add to 51 previous warning letters issued by the FDA since 2015 to other manufacturers of products containing CBD who were violating the Federal Food, Drug, and Cosmetic Act.
In a news release, the agency explained that its two most recent letters, sent to Honest Globe Inc. on March 15 and BioLyte Laboratories LLC on March 18, were issued because CBD has “known pharmacologic effects on humans, with demonstrated risks, it cannot be legally marketed as an inactive ingredient in OTC drug products that are not reviewed and approved by the FDA.” They also describe the companies’ failures to comply with current good manufacturing practices.
“The FDA continues to alert the public to potential safety and efficacy concerns with unapproved CBD products sold online and in stores across the country,” FDA Principal Deputy Commissioner Amy P. Abernethy, MD, PhD, said in the release. “It’s important that consumers understand that the FDA has only approved one drug containing CBD as an ingredient [Epidiolex]. These other, unapproved, CBD products may have dangerous health impacts and side effects. We remain focused on exploring potential pathways for CBD products to be lawfully marketed while also educating the public about these outstanding questions of CBD’s safety. Meanwhile, we will continue to monitor and take action, as needed, against companies that unlawfully market their products – prioritizing those that pose a risk to public health.”
The specific products from Santa Ana, Calif.–based Honest Globe that the FDA called unapproved new drugs and misbranded under the Federal Food, Drug, and Cosmetic Act included Elixicure Original Pain Relief and Elixicure Lavender Pain Relief, both of which were described as containing CBD. Products from Grand Rapids, Mich.–based BioLyte Laboratories LLC that the FDA similarly cited for violations included Silver Gel, Silver Gel with Aloe, Silver Liquid Supplement, Therapeutic Pain Gel, Pain Relief Cream, and Magnesium Oil Spray.
The agency has asked the two companies to respond to its letters within 15 working days, “stating how they will address these violations or providing their reasoning and supporting information as to why they believe these products are not in violation of the law. Failure to adequately address the violations promptly may result in legal action, including product seizure and/or injunction.”
The Food and Drug Administration has warned two manufacturers about illegal marketing of drugs containing cannabidiol (CBD) for over-the-counter use without an approved new drug application, for using substandard manufacturing processes, and for failure to comply with current good manufacturing practices. These warnings add to 51 previous warning letters issued by the FDA since 2015 to other manufacturers of products containing CBD who were violating the Federal Food, Drug, and Cosmetic Act.
In a news release, the agency explained that its two most recent letters, sent to Honest Globe Inc. on March 15 and BioLyte Laboratories LLC on March 18, were issued because CBD has “known pharmacologic effects on humans, with demonstrated risks, it cannot be legally marketed as an inactive ingredient in OTC drug products that are not reviewed and approved by the FDA.” They also describe the companies’ failures to comply with current good manufacturing practices.
“The FDA continues to alert the public to potential safety and efficacy concerns with unapproved CBD products sold online and in stores across the country,” FDA Principal Deputy Commissioner Amy P. Abernethy, MD, PhD, said in the release. “It’s important that consumers understand that the FDA has only approved one drug containing CBD as an ingredient [Epidiolex]. These other, unapproved, CBD products may have dangerous health impacts and side effects. We remain focused on exploring potential pathways for CBD products to be lawfully marketed while also educating the public about these outstanding questions of CBD’s safety. Meanwhile, we will continue to monitor and take action, as needed, against companies that unlawfully market their products – prioritizing those that pose a risk to public health.”
The specific products from Santa Ana, Calif.–based Honest Globe that the FDA called unapproved new drugs and misbranded under the Federal Food, Drug, and Cosmetic Act included Elixicure Original Pain Relief and Elixicure Lavender Pain Relief, both of which were described as containing CBD. Products from Grand Rapids, Mich.–based BioLyte Laboratories LLC that the FDA similarly cited for violations included Silver Gel, Silver Gel with Aloe, Silver Liquid Supplement, Therapeutic Pain Gel, Pain Relief Cream, and Magnesium Oil Spray.
The agency has asked the two companies to respond to its letters within 15 working days, “stating how they will address these violations or providing their reasoning and supporting information as to why they believe these products are not in violation of the law. Failure to adequately address the violations promptly may result in legal action, including product seizure and/or injunction.”
The Food and Drug Administration has warned two manufacturers about illegal marketing of drugs containing cannabidiol (CBD) for over-the-counter use without an approved new drug application, for using substandard manufacturing processes, and for failure to comply with current good manufacturing practices. These warnings add to 51 previous warning letters issued by the FDA since 2015 to other manufacturers of products containing CBD who were violating the Federal Food, Drug, and Cosmetic Act.
In a news release, the agency explained that its two most recent letters, sent to Honest Globe Inc. on March 15 and BioLyte Laboratories LLC on March 18, were issued because CBD has “known pharmacologic effects on humans, with demonstrated risks, it cannot be legally marketed as an inactive ingredient in OTC drug products that are not reviewed and approved by the FDA.” They also describe the companies’ failures to comply with current good manufacturing practices.
“The FDA continues to alert the public to potential safety and efficacy concerns with unapproved CBD products sold online and in stores across the country,” FDA Principal Deputy Commissioner Amy P. Abernethy, MD, PhD, said in the release. “It’s important that consumers understand that the FDA has only approved one drug containing CBD as an ingredient [Epidiolex]. These other, unapproved, CBD products may have dangerous health impacts and side effects. We remain focused on exploring potential pathways for CBD products to be lawfully marketed while also educating the public about these outstanding questions of CBD’s safety. Meanwhile, we will continue to monitor and take action, as needed, against companies that unlawfully market their products – prioritizing those that pose a risk to public health.”
The specific products from Santa Ana, Calif.–based Honest Globe that the FDA called unapproved new drugs and misbranded under the Federal Food, Drug, and Cosmetic Act included Elixicure Original Pain Relief and Elixicure Lavender Pain Relief, both of which were described as containing CBD. Products from Grand Rapids, Mich.–based BioLyte Laboratories LLC that the FDA similarly cited for violations included Silver Gel, Silver Gel with Aloe, Silver Liquid Supplement, Therapeutic Pain Gel, Pain Relief Cream, and Magnesium Oil Spray.
The agency has asked the two companies to respond to its letters within 15 working days, “stating how they will address these violations or providing their reasoning and supporting information as to why they believe these products are not in violation of the law. Failure to adequately address the violations promptly may result in legal action, including product seizure and/or injunction.”
Novel lupus therapies take center stage
It’s been a banner year for treatment advances in systemic lupus erythematosus (SLE), with two drugs gaining approval for lupus nephritis while other promising molecules with novel mechanisms of action advanced smartly through the developmental pipeline, speakers agreed at the 2021 Rheumatology Winter Clinical Symposium.
“I think the most important thing in rheumatology in the last year is where we are now with lupus. With two drugs being approved for lupus nephritis, I think that’s really huge as we talk about treat-to-target,” said Alvin F. Wells, MD, PhD, a rheumatologist in Franklin, Wisc.
Martin Bergman, MD, concurred.
“Lupus has been blowing up in the past year. We have two new medications for lupus nephritis, we have two or three new mechanisms of action for therapy. I think that was one of the biggest things in rheumatology in the past year,” said Dr. Bergman, a rheumatologist at Drexel University in Philadelphia and in private practice in Ridley Park, Pa.
Together with Roy Fleischmann, MD, Dr. Wells spotlighted promising new molecules for the treatment of SLE, giant cell arteritis, vasculitis, rheumatoid arthritis, and osteoarthritis.
SLE
The two drugs approved in recent months specifically for lupus nephritis are voclosporin (Lupkynis) and belimumab (Benlysta), which has been approved for lupus for a decade. Voclosporin, an oral calcineurin inhibitor, is a modification of cyclosporine offering significant advantages over the older drug: It’s more potent, requires no dose titration, has a better safety profile, and is metabolized more quickly.
“A safer and easier-to-use calcineurin inhibitor is going to be huge,” Dr. Wells predicted.
Up for Food and Drug Administration review in the coming year on the basis of the positive phase 3 TULIP-1 and TULIP-2 trials is anifrolumab, a monoclonal antibody that binds to the type 1 interferon receptor subunit 1d. At 52 weeks in the pooled analysis, one or more SLE flares occurred in 33.6% of patients on anifrolumab and 42.9% of placebo-treated controls.
“This is not a blockbuster, but it’s a worthwhile addition, like belimumab,” according to Dr. Fleischmann, a rheumatologist at the University of Texas, Dallas.
Dr. Wells concurred, with a reservation: In a subgroup analysis of the TULIP trials, anifrolumab wasn’t significantly better than placebo in black patients, who tend to have more severe and tough-to-treat renal disease.
“Anifrolumab doesn’t look as effective as some other agents, and I’d be disinclined to give it to my black patients,” the rheumatologist said.
Dr. Fleischmann was far more enthusiastic about obinutuzumab (Gazyva), a humanized anti-CD20 monoclonal antibody already approved for the treatment of chronic lymphocytic leukemia and follicular lymphoma.
“It’s an anti-CD20, like rituximab. But it’s better than rituximab, it’s much more effective,” he said.
He pointed to the phase 2 NOBILITY trial, in which 125 patients with class III/IV lupus nephritis were randomized to a 1,000-mg infusion of obinutuzumab or placebo at weeks 0, 2, 24, and 26 and followed for 2 years. The complete renal response rate at 104 weeks in the obinutuzumab group was 41% and the partial renal response rate was 13%, compared to 23% and 6% in controls. The obinutuzumab group also did significantly better in terms of improvement in complement levels, double-stranded DNA, and estimated glomerular filtration rate. All this was accomplished even though the reduction in peripheral B cells dropped from 93% at week 24 to just 16% at week 104. This suggests that tissue levels of B cells in the kidney, joints, and skin may be more important than circulating B cell levels.
“This looks like a very promising agent for patients with lupus nephritis,” Dr. Wells said. “The fact that they got this long-term effect for 2 years with just four infusions is really impressive.”
Another promising drug is iberdomide, an oral modulator of the E3 ubiquitin ligase complex which decreases plasmacytoid dendritic cells and B cells while increasing T regulatory cells. In a phase 2b clinical trial in 288 patients with active SLE, all on background standard-of-care therapy, a 4-point or greater reduction in the SLE Responder Index (SRI-4) at week 24 was achieved in 54.3% of the group on iberdomide at 0.45 mg/day, a significantly better result than the 34.9% rate with placebo. This absolute 19.4% difference was even greater in the subgroup of patients with a high baseline level of the transcription factor Aiolos, where the absolute improvement over placebo was 32.9%. Similarly, the benefit of iberdomide was also enhanced in patients with a high baseline level of type 1 interferon, where the absolute difference was 26.8%. This raises the prospect that a bioassay could be developed to predict the likelihood of a favorable clinical response to the drug. Iberdomide was well tolerated, with fewer severe adverse events than in the control group.
A humanized monoclonal antibody known for now as BIIB059 demonstrated efficacy and was well tolerated in the phase 2 LILAC trial. BIIB059 binds to blood dendritic cell antigen 2 (BDCA2), a receptor specific to plasmacytoid dendritic cells, resulting in decreased production of type 1 interferon and other inflammatory cytokines. The LILAC trial included 132 SLE patients with active arthritis and skin disease who received subcutaneous injections of BIIB059 at 450 mg or placebo every 4 weeks, with an extra dose at week 2. The primary endpoint was met, with an absolute 15-joint reduction in the total number of tender or swollen joints from baseline to week 24 in the BIIB059 group, compared to an 11.6-joint reduction with placebo. In addition, the likelihood of an SRI-4 response at week 24 was 3.49-fold greater with BIIB059 than with placebo.
Dr. Wells noted that the BIIB059 group showed continued improvement from week 12 to week 24, unlike the response pattern seen with many biologics for rheumatoid arthritis, where a plateau is reached by 8-12 weeks.
Vasculitis
The positive results for the C5a receptor inhibitor avacopan for treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in the phase-3 ADVOCATE trial have been hailed by some rheumatologists as a major breakthrough, but Dr. Fleischmann isn’t so sure.
The trial randomized 331 patients to oral avacopan at 30 mg twice daily or oral prednisone, with all patients on either cyclophosphamide or rituximab. Avacopan was noninferior to prednisone in terms of remission at week 26, but superior to prednisone for sustained taper at week 52. The rate of serious adverse events was 45.1% with prednisone and 42.2% in the avacopan arm.
“This is a drug that’s going to be much, much more expensive than prednisone. There were people in our group who were ecstatic that this drug is going to come, but how much it’s going to be used, I don’t know,” Dr. Fleischmann said.
Dr. Wells said cost-benefit analyses will be needed in order to learn if avacopan’s anticipated high sticker price is offset by the cost of serious corticosteroid side effects such as avascular necrosis.
Giant cell arteritis
Mavrilimumab is a human monoclonal antibody that inhibits human granulocyte macrophage colony stimulating factor receptor alpha. It demonstrated impressive efficacy in a phase 2, double-blind, randomized, placebo-controlled trial conducted in 70 patients with biopsy-confirmed giant cell arteritis. Participants were on corticosteroids until they went into remission and were then randomized to mavrilimumab or placebo, with the steroids stopped. By week 26, 19% of patients in the mavrilimumab arm had flared, as compared to 46.4% of controls.
“This is a game changer,” Dr. Wells declared. “I struggle with these patients because I can’t get the IL-6 drugs approved for them. I need something else.”
Dr. Fleischmann has a good idea how he’ll use mavrilimumab, if it wins approval: “I think this is clearly a drug you would use in a patient you can’t get off steroids and you’re having all the steroid toxicity. I don’t know that you’d use it right away.”
Osteoarthritis
Dr. Fleischmann predicted that tanezumab, a monoclonal antibody directed against nerve growth factor, will win FDA approval in 2021 for the treatment of osteoarthritis pain in patients with an inadequate response or intolerance to standard-of-care NSAIDs and opioids. But he cautioned his colleagues not to expect too much from the biologic, which has a long and checkered developmental history.
“It works better than placebo. It does not work better than an NSAID or an opioid. So it should be reasonable in patients who cannot take an NSAID or cannot or will not take an opioid,” he said.
There are safety issues to be aware of with tanezumab, he added: clinically significant increased risks of peripheral neuropathy and joint space narrowing.
Rheumatoid arthritis
Dr. Wells thought one of the most interesting novel therapies for RA in the past year didn’t involve a pharmaceutical, but rather noninvasive auricular branch stimulation of the vagus nerve. He cited an open-label, 12-week, uncontrolled study in 27 patients with active RA who wore an ear clip for vagal nerve stimulation for 12 weeks. The mean Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) – the primary study endpoint – improved from 6.30 at baseline to 3.76 at week 12. The number of tender joints dropped from 12.17 to 4.7, while the swollen joint count went from 7.0 to 3.44. Pain scores improved from 75.23 to 43.3. Scores on the Health Assessment Questionnaire Disability Index improved from 1.59 to 1.05. There was no significant change in CRP. All in all, a modest clinical effect achieved noninvasively.
“The thing that did it for me was the effect on MRI from baseline: decreased synovitis, osteitis, and bone erosion scores,” Dr. Wells said. “This is noninvasive, so patients who want to do medical marijuana or CBD can put an earring on their auricular nerve.”
Dr. Fleischmann scoffed. “An open-label study, 27 patients? Let me see the real study,” he quipped.
Dr. Fleischmann reported receiving clinical trial research grants from and serving as a consultant to more than a dozen pharmaceutical companies. Dr. Wells serves as a consultant to MiCare Path.
It’s been a banner year for treatment advances in systemic lupus erythematosus (SLE), with two drugs gaining approval for lupus nephritis while other promising molecules with novel mechanisms of action advanced smartly through the developmental pipeline, speakers agreed at the 2021 Rheumatology Winter Clinical Symposium.
“I think the most important thing in rheumatology in the last year is where we are now with lupus. With two drugs being approved for lupus nephritis, I think that’s really huge as we talk about treat-to-target,” said Alvin F. Wells, MD, PhD, a rheumatologist in Franklin, Wisc.
Martin Bergman, MD, concurred.
“Lupus has been blowing up in the past year. We have two new medications for lupus nephritis, we have two or three new mechanisms of action for therapy. I think that was one of the biggest things in rheumatology in the past year,” said Dr. Bergman, a rheumatologist at Drexel University in Philadelphia and in private practice in Ridley Park, Pa.
Together with Roy Fleischmann, MD, Dr. Wells spotlighted promising new molecules for the treatment of SLE, giant cell arteritis, vasculitis, rheumatoid arthritis, and osteoarthritis.
SLE
The two drugs approved in recent months specifically for lupus nephritis are voclosporin (Lupkynis) and belimumab (Benlysta), which has been approved for lupus for a decade. Voclosporin, an oral calcineurin inhibitor, is a modification of cyclosporine offering significant advantages over the older drug: It’s more potent, requires no dose titration, has a better safety profile, and is metabolized more quickly.
“A safer and easier-to-use calcineurin inhibitor is going to be huge,” Dr. Wells predicted.
Up for Food and Drug Administration review in the coming year on the basis of the positive phase 3 TULIP-1 and TULIP-2 trials is anifrolumab, a monoclonal antibody that binds to the type 1 interferon receptor subunit 1d. At 52 weeks in the pooled analysis, one or more SLE flares occurred in 33.6% of patients on anifrolumab and 42.9% of placebo-treated controls.
“This is not a blockbuster, but it’s a worthwhile addition, like belimumab,” according to Dr. Fleischmann, a rheumatologist at the University of Texas, Dallas.
Dr. Wells concurred, with a reservation: In a subgroup analysis of the TULIP trials, anifrolumab wasn’t significantly better than placebo in black patients, who tend to have more severe and tough-to-treat renal disease.
“Anifrolumab doesn’t look as effective as some other agents, and I’d be disinclined to give it to my black patients,” the rheumatologist said.
Dr. Fleischmann was far more enthusiastic about obinutuzumab (Gazyva), a humanized anti-CD20 monoclonal antibody already approved for the treatment of chronic lymphocytic leukemia and follicular lymphoma.
“It’s an anti-CD20, like rituximab. But it’s better than rituximab, it’s much more effective,” he said.
He pointed to the phase 2 NOBILITY trial, in which 125 patients with class III/IV lupus nephritis were randomized to a 1,000-mg infusion of obinutuzumab or placebo at weeks 0, 2, 24, and 26 and followed for 2 years. The complete renal response rate at 104 weeks in the obinutuzumab group was 41% and the partial renal response rate was 13%, compared to 23% and 6% in controls. The obinutuzumab group also did significantly better in terms of improvement in complement levels, double-stranded DNA, and estimated glomerular filtration rate. All this was accomplished even though the reduction in peripheral B cells dropped from 93% at week 24 to just 16% at week 104. This suggests that tissue levels of B cells in the kidney, joints, and skin may be more important than circulating B cell levels.
“This looks like a very promising agent for patients with lupus nephritis,” Dr. Wells said. “The fact that they got this long-term effect for 2 years with just four infusions is really impressive.”
Another promising drug is iberdomide, an oral modulator of the E3 ubiquitin ligase complex which decreases plasmacytoid dendritic cells and B cells while increasing T regulatory cells. In a phase 2b clinical trial in 288 patients with active SLE, all on background standard-of-care therapy, a 4-point or greater reduction in the SLE Responder Index (SRI-4) at week 24 was achieved in 54.3% of the group on iberdomide at 0.45 mg/day, a significantly better result than the 34.9% rate with placebo. This absolute 19.4% difference was even greater in the subgroup of patients with a high baseline level of the transcription factor Aiolos, where the absolute improvement over placebo was 32.9%. Similarly, the benefit of iberdomide was also enhanced in patients with a high baseline level of type 1 interferon, where the absolute difference was 26.8%. This raises the prospect that a bioassay could be developed to predict the likelihood of a favorable clinical response to the drug. Iberdomide was well tolerated, with fewer severe adverse events than in the control group.
A humanized monoclonal antibody known for now as BIIB059 demonstrated efficacy and was well tolerated in the phase 2 LILAC trial. BIIB059 binds to blood dendritic cell antigen 2 (BDCA2), a receptor specific to plasmacytoid dendritic cells, resulting in decreased production of type 1 interferon and other inflammatory cytokines. The LILAC trial included 132 SLE patients with active arthritis and skin disease who received subcutaneous injections of BIIB059 at 450 mg or placebo every 4 weeks, with an extra dose at week 2. The primary endpoint was met, with an absolute 15-joint reduction in the total number of tender or swollen joints from baseline to week 24 in the BIIB059 group, compared to an 11.6-joint reduction with placebo. In addition, the likelihood of an SRI-4 response at week 24 was 3.49-fold greater with BIIB059 than with placebo.
Dr. Wells noted that the BIIB059 group showed continued improvement from week 12 to week 24, unlike the response pattern seen with many biologics for rheumatoid arthritis, where a plateau is reached by 8-12 weeks.
Vasculitis
The positive results for the C5a receptor inhibitor avacopan for treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in the phase-3 ADVOCATE trial have been hailed by some rheumatologists as a major breakthrough, but Dr. Fleischmann isn’t so sure.
The trial randomized 331 patients to oral avacopan at 30 mg twice daily or oral prednisone, with all patients on either cyclophosphamide or rituximab. Avacopan was noninferior to prednisone in terms of remission at week 26, but superior to prednisone for sustained taper at week 52. The rate of serious adverse events was 45.1% with prednisone and 42.2% in the avacopan arm.
“This is a drug that’s going to be much, much more expensive than prednisone. There were people in our group who were ecstatic that this drug is going to come, but how much it’s going to be used, I don’t know,” Dr. Fleischmann said.
Dr. Wells said cost-benefit analyses will be needed in order to learn if avacopan’s anticipated high sticker price is offset by the cost of serious corticosteroid side effects such as avascular necrosis.
Giant cell arteritis
Mavrilimumab is a human monoclonal antibody that inhibits human granulocyte macrophage colony stimulating factor receptor alpha. It demonstrated impressive efficacy in a phase 2, double-blind, randomized, placebo-controlled trial conducted in 70 patients with biopsy-confirmed giant cell arteritis. Participants were on corticosteroids until they went into remission and were then randomized to mavrilimumab or placebo, with the steroids stopped. By week 26, 19% of patients in the mavrilimumab arm had flared, as compared to 46.4% of controls.
“This is a game changer,” Dr. Wells declared. “I struggle with these patients because I can’t get the IL-6 drugs approved for them. I need something else.”
Dr. Fleischmann has a good idea how he’ll use mavrilimumab, if it wins approval: “I think this is clearly a drug you would use in a patient you can’t get off steroids and you’re having all the steroid toxicity. I don’t know that you’d use it right away.”
Osteoarthritis
Dr. Fleischmann predicted that tanezumab, a monoclonal antibody directed against nerve growth factor, will win FDA approval in 2021 for the treatment of osteoarthritis pain in patients with an inadequate response or intolerance to standard-of-care NSAIDs and opioids. But he cautioned his colleagues not to expect too much from the biologic, which has a long and checkered developmental history.
“It works better than placebo. It does not work better than an NSAID or an opioid. So it should be reasonable in patients who cannot take an NSAID or cannot or will not take an opioid,” he said.
There are safety issues to be aware of with tanezumab, he added: clinically significant increased risks of peripheral neuropathy and joint space narrowing.
Rheumatoid arthritis
Dr. Wells thought one of the most interesting novel therapies for RA in the past year didn’t involve a pharmaceutical, but rather noninvasive auricular branch stimulation of the vagus nerve. He cited an open-label, 12-week, uncontrolled study in 27 patients with active RA who wore an ear clip for vagal nerve stimulation for 12 weeks. The mean Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) – the primary study endpoint – improved from 6.30 at baseline to 3.76 at week 12. The number of tender joints dropped from 12.17 to 4.7, while the swollen joint count went from 7.0 to 3.44. Pain scores improved from 75.23 to 43.3. Scores on the Health Assessment Questionnaire Disability Index improved from 1.59 to 1.05. There was no significant change in CRP. All in all, a modest clinical effect achieved noninvasively.
“The thing that did it for me was the effect on MRI from baseline: decreased synovitis, osteitis, and bone erosion scores,” Dr. Wells said. “This is noninvasive, so patients who want to do medical marijuana or CBD can put an earring on their auricular nerve.”
Dr. Fleischmann scoffed. “An open-label study, 27 patients? Let me see the real study,” he quipped.
Dr. Fleischmann reported receiving clinical trial research grants from and serving as a consultant to more than a dozen pharmaceutical companies. Dr. Wells serves as a consultant to MiCare Path.
It’s been a banner year for treatment advances in systemic lupus erythematosus (SLE), with two drugs gaining approval for lupus nephritis while other promising molecules with novel mechanisms of action advanced smartly through the developmental pipeline, speakers agreed at the 2021 Rheumatology Winter Clinical Symposium.
“I think the most important thing in rheumatology in the last year is where we are now with lupus. With two drugs being approved for lupus nephritis, I think that’s really huge as we talk about treat-to-target,” said Alvin F. Wells, MD, PhD, a rheumatologist in Franklin, Wisc.
Martin Bergman, MD, concurred.
“Lupus has been blowing up in the past year. We have two new medications for lupus nephritis, we have two or three new mechanisms of action for therapy. I think that was one of the biggest things in rheumatology in the past year,” said Dr. Bergman, a rheumatologist at Drexel University in Philadelphia and in private practice in Ridley Park, Pa.
Together with Roy Fleischmann, MD, Dr. Wells spotlighted promising new molecules for the treatment of SLE, giant cell arteritis, vasculitis, rheumatoid arthritis, and osteoarthritis.
SLE
The two drugs approved in recent months specifically for lupus nephritis are voclosporin (Lupkynis) and belimumab (Benlysta), which has been approved for lupus for a decade. Voclosporin, an oral calcineurin inhibitor, is a modification of cyclosporine offering significant advantages over the older drug: It’s more potent, requires no dose titration, has a better safety profile, and is metabolized more quickly.
“A safer and easier-to-use calcineurin inhibitor is going to be huge,” Dr. Wells predicted.
Up for Food and Drug Administration review in the coming year on the basis of the positive phase 3 TULIP-1 and TULIP-2 trials is anifrolumab, a monoclonal antibody that binds to the type 1 interferon receptor subunit 1d. At 52 weeks in the pooled analysis, one or more SLE flares occurred in 33.6% of patients on anifrolumab and 42.9% of placebo-treated controls.
“This is not a blockbuster, but it’s a worthwhile addition, like belimumab,” according to Dr. Fleischmann, a rheumatologist at the University of Texas, Dallas.
Dr. Wells concurred, with a reservation: In a subgroup analysis of the TULIP trials, anifrolumab wasn’t significantly better than placebo in black patients, who tend to have more severe and tough-to-treat renal disease.
“Anifrolumab doesn’t look as effective as some other agents, and I’d be disinclined to give it to my black patients,” the rheumatologist said.
Dr. Fleischmann was far more enthusiastic about obinutuzumab (Gazyva), a humanized anti-CD20 monoclonal antibody already approved for the treatment of chronic lymphocytic leukemia and follicular lymphoma.
“It’s an anti-CD20, like rituximab. But it’s better than rituximab, it’s much more effective,” he said.
He pointed to the phase 2 NOBILITY trial, in which 125 patients with class III/IV lupus nephritis were randomized to a 1,000-mg infusion of obinutuzumab or placebo at weeks 0, 2, 24, and 26 and followed for 2 years. The complete renal response rate at 104 weeks in the obinutuzumab group was 41% and the partial renal response rate was 13%, compared to 23% and 6% in controls. The obinutuzumab group also did significantly better in terms of improvement in complement levels, double-stranded DNA, and estimated glomerular filtration rate. All this was accomplished even though the reduction in peripheral B cells dropped from 93% at week 24 to just 16% at week 104. This suggests that tissue levels of B cells in the kidney, joints, and skin may be more important than circulating B cell levels.
“This looks like a very promising agent for patients with lupus nephritis,” Dr. Wells said. “The fact that they got this long-term effect for 2 years with just four infusions is really impressive.”
Another promising drug is iberdomide, an oral modulator of the E3 ubiquitin ligase complex which decreases plasmacytoid dendritic cells and B cells while increasing T regulatory cells. In a phase 2b clinical trial in 288 patients with active SLE, all on background standard-of-care therapy, a 4-point or greater reduction in the SLE Responder Index (SRI-4) at week 24 was achieved in 54.3% of the group on iberdomide at 0.45 mg/day, a significantly better result than the 34.9% rate with placebo. This absolute 19.4% difference was even greater in the subgroup of patients with a high baseline level of the transcription factor Aiolos, where the absolute improvement over placebo was 32.9%. Similarly, the benefit of iberdomide was also enhanced in patients with a high baseline level of type 1 interferon, where the absolute difference was 26.8%. This raises the prospect that a bioassay could be developed to predict the likelihood of a favorable clinical response to the drug. Iberdomide was well tolerated, with fewer severe adverse events than in the control group.
A humanized monoclonal antibody known for now as BIIB059 demonstrated efficacy and was well tolerated in the phase 2 LILAC trial. BIIB059 binds to blood dendritic cell antigen 2 (BDCA2), a receptor specific to plasmacytoid dendritic cells, resulting in decreased production of type 1 interferon and other inflammatory cytokines. The LILAC trial included 132 SLE patients with active arthritis and skin disease who received subcutaneous injections of BIIB059 at 450 mg or placebo every 4 weeks, with an extra dose at week 2. The primary endpoint was met, with an absolute 15-joint reduction in the total number of tender or swollen joints from baseline to week 24 in the BIIB059 group, compared to an 11.6-joint reduction with placebo. In addition, the likelihood of an SRI-4 response at week 24 was 3.49-fold greater with BIIB059 than with placebo.
Dr. Wells noted that the BIIB059 group showed continued improvement from week 12 to week 24, unlike the response pattern seen with many biologics for rheumatoid arthritis, where a plateau is reached by 8-12 weeks.
Vasculitis
The positive results for the C5a receptor inhibitor avacopan for treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in the phase-3 ADVOCATE trial have been hailed by some rheumatologists as a major breakthrough, but Dr. Fleischmann isn’t so sure.
The trial randomized 331 patients to oral avacopan at 30 mg twice daily or oral prednisone, with all patients on either cyclophosphamide or rituximab. Avacopan was noninferior to prednisone in terms of remission at week 26, but superior to prednisone for sustained taper at week 52. The rate of serious adverse events was 45.1% with prednisone and 42.2% in the avacopan arm.
“This is a drug that’s going to be much, much more expensive than prednisone. There were people in our group who were ecstatic that this drug is going to come, but how much it’s going to be used, I don’t know,” Dr. Fleischmann said.
Dr. Wells said cost-benefit analyses will be needed in order to learn if avacopan’s anticipated high sticker price is offset by the cost of serious corticosteroid side effects such as avascular necrosis.
Giant cell arteritis
Mavrilimumab is a human monoclonal antibody that inhibits human granulocyte macrophage colony stimulating factor receptor alpha. It demonstrated impressive efficacy in a phase 2, double-blind, randomized, placebo-controlled trial conducted in 70 patients with biopsy-confirmed giant cell arteritis. Participants were on corticosteroids until they went into remission and were then randomized to mavrilimumab or placebo, with the steroids stopped. By week 26, 19% of patients in the mavrilimumab arm had flared, as compared to 46.4% of controls.
“This is a game changer,” Dr. Wells declared. “I struggle with these patients because I can’t get the IL-6 drugs approved for them. I need something else.”
Dr. Fleischmann has a good idea how he’ll use mavrilimumab, if it wins approval: “I think this is clearly a drug you would use in a patient you can’t get off steroids and you’re having all the steroid toxicity. I don’t know that you’d use it right away.”
Osteoarthritis
Dr. Fleischmann predicted that tanezumab, a monoclonal antibody directed against nerve growth factor, will win FDA approval in 2021 for the treatment of osteoarthritis pain in patients with an inadequate response or intolerance to standard-of-care NSAIDs and opioids. But he cautioned his colleagues not to expect too much from the biologic, which has a long and checkered developmental history.
“It works better than placebo. It does not work better than an NSAID or an opioid. So it should be reasonable in patients who cannot take an NSAID or cannot or will not take an opioid,” he said.
There are safety issues to be aware of with tanezumab, he added: clinically significant increased risks of peripheral neuropathy and joint space narrowing.
Rheumatoid arthritis
Dr. Wells thought one of the most interesting novel therapies for RA in the past year didn’t involve a pharmaceutical, but rather noninvasive auricular branch stimulation of the vagus nerve. He cited an open-label, 12-week, uncontrolled study in 27 patients with active RA who wore an ear clip for vagal nerve stimulation for 12 weeks. The mean Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) – the primary study endpoint – improved from 6.30 at baseline to 3.76 at week 12. The number of tender joints dropped from 12.17 to 4.7, while the swollen joint count went from 7.0 to 3.44. Pain scores improved from 75.23 to 43.3. Scores on the Health Assessment Questionnaire Disability Index improved from 1.59 to 1.05. There was no significant change in CRP. All in all, a modest clinical effect achieved noninvasively.
“The thing that did it for me was the effect on MRI from baseline: decreased synovitis, osteitis, and bone erosion scores,” Dr. Wells said. “This is noninvasive, so patients who want to do medical marijuana or CBD can put an earring on their auricular nerve.”
Dr. Fleischmann scoffed. “An open-label study, 27 patients? Let me see the real study,” he quipped.
Dr. Fleischmann reported receiving clinical trial research grants from and serving as a consultant to more than a dozen pharmaceutical companies. Dr. Wells serves as a consultant to MiCare Path.
FROM RWCS 2021
Telemedicine models show some benefit in OA
Remote interventions using an Internet-based app and telephone outreach to engage patients with osteoarthritis to self-manage their disease have demonstrated the potential to improve some symptoms, at least in the short term, showing the potential for tools to interact with OA patients without having them come into an office or clinic.
Remote interaction using these two forms of telemedicine – one a sophisticated digital platform, the other using a device that’s been around for almost 150 years – may have greater utility for keeping physicians connected with their OA patients during the COVID-19 pandemic, OA experts said in an interview.
“This is certainly relevant during the pandemic, but this has been of high interest for years as well, as researchers and clinicians have been seeking the best ways to reach patients with these types of programs,” said Kelli Allen, PhD, a research health scientist at the University of North Carolina at Chapel Hill.
Two separate studies evaluated the telemedicine platforms. In JAMA Internal Medicine, researchers reported that telephone-based cognitive-behavioral therapy (CBT) for patients aged 60 and older with OA and insomnia led to improved sleep, fatigue and, to a lesser extent, pain, in a randomized, controlled trial with 327 patients.
A separate randomized, controlled trial of 105 OA patients at the University of Nottingham (England), published in JAMA Network Open, reported that users of a smartphone-based exercise intervention app had greater improvements in pain and function than did controls.
“I think these two studies represent a first step in terms of moving forward, and certainly the interventions could be refined and potentially combined together for patients in the future,” said C. Kent Kwoh, MD, director of the University of Arizona Arthritis Center in Tucson.
Phone-based CBT study
The telephone-based CBT study consisted of two groups: the CBT group (n = 163) who completed six 20- to 30-minute telephone calls over 8 weeks, kept daily diaries, and received tailored educational materials and an education-only group (n = 164). At 2 months after treatment, Insomnia Severity Index scores decreased 8.1 points on average in the CBT group versus 4.8 points in the education-only patients (P < .001).
That variation between the intervention group and controls was sustained out to a year: 7.7 points lower than baseline versus 4.7 points lower. At the same time point, 56.3% of the CBT group remained in remission with Insomnia Severity Index scores less than 7 versus 25.8% of controls. Fatigue outcomes were similarly disparate between the groups.
Pain outcomes were a different story, however. “Post treatment, significant differences were observed for pain, but these differences were not sustained at 12-month follow-up,” first author Susan M. McCurry, PhD, a clinical psychologist and faculty member at the University of Washington, Seattle, and colleagues wrote.
“I think their positive findings illustrate that remotely delivered interventions can be ‘low tech’ and still effective,” Dr. Allen said of the CBT phone study. She noted that complete case data were available for 282 of 327 patients. “The high rate of session attendance suggests that they chose a delivery modality appropriate for their target patient group.”
The scalability of the telephone model is noteworthy, Dr. Kwoh said. “Having a telemedicine intervention that could be scaled a little more easily rather than an in-person intervention, and having individualized treatment, that’s beneficial, as is targeting two symptoms that are very bothersome and burdensome to patients with OA: insomnia and fatigue.” Following patients out to 12 months is a strength of the study, he added.
Smartphone app–based exercise study
The U.K. study evaluated 6-week outcomes of 48 patients with knee OA who used a proprietary app-based exercise program (Joint Academy) and 57 controls who used traditional self-management. The app provided daily exercises and texts, along with email and smartphone reminders. The app was derived from the Better Management of Patients with OA program initiated in Sweden in 2008 that used OA treatment guidelines for education and exercise in person in primary care clinics.
App users showed a 1.5-point reduction in numeric rating scale (NRS) pain score at 6 weeks versus virtually no change in controls (P < .001). In terms of secondary outcomes, pain scores improved 2.2 points on average for app users versus 1.2 for controls (P = .02), with similar improvements recorded in both stiffness and physical function.
Average change in the 30-second sit-to-stand test measured 4.5 for the app users and 1.2 for the usual-care group (P < .001). The study found no difference between the two groups in changes in temporal summation, conditional pain modulation, or Arthritis Research UK Musculoskeletal Health Questionnaire scores.
First author Sameer Akram Gohir, MSc, PhD, and colleagues wrote that the reasons for differences in outcomes between app users and controls aren’t clear. “The superior outcome in the intervention group may depend on the content and context in the app, including a combination of standardized exercises and information, as well as using a digital delivery system.”
Data gathering was cut short because of COVID-19 restrictions in the United Kingdom, as 27 patients missed their in-person follow-up visits. That was one shortcoming of the study, Dr. Kwoh noted.
“Given the caveats certainly they were able to show robust changes in terms of decreased pain, and also improvement in a variety of performance measures. Certainly this may be beneficial – we don’t know – in terms of cost-effectiveness, but it may be beneficial for insurance companies to adapt such a program,” he said, adding that future studies into the cost effectiveness of the digital platform would be in order.
“Certainly, if this program were to decrease physician visits or postpone the need for joint replacement for individuals, then it could be certainly very cost effective,” Dr. Kwoh said.
The completion rate among patients in the study – almost 90% – was “impressive,” Dr. Allen said. “However, this is a relatively short-term study, and I think an important question for future research is whether patients continue with this level of engagement for a longer period of time.”
Dr. McCurry had no relevant financial relationships to disclose. The CBT phone study received funding from the Public Health Service and the National Institute on Aging. Coauthors disclosed relationships with Campbell Alliance Group, Mapi Research Trust, and Pfizer. Dr. Gohir reported no relevant financial relationships. The study received funding from the Versus Arthritis UK Plan Center, the National Institute for Health Research Nottingham Biomedical Research Center, and Pfizer Global. The Joint Academy provided software for the study. A coauthor reported a financial relationships with Pfizer. Dr. Kwoh said that in the past year he has consulted for Express Scripts, Kolon Tissue Gene, LG Chem, and Regeneron. In the past year, he also received institutional grants for clinical trials from AbbVie, Cumberland, Eicos, Eli Lilly, GlaxoSmithKline, Mitsubishi, and Pfizer. Dr. Allen had no relevant financial relationships to disclose.
Remote interventions using an Internet-based app and telephone outreach to engage patients with osteoarthritis to self-manage their disease have demonstrated the potential to improve some symptoms, at least in the short term, showing the potential for tools to interact with OA patients without having them come into an office or clinic.
Remote interaction using these two forms of telemedicine – one a sophisticated digital platform, the other using a device that’s been around for almost 150 years – may have greater utility for keeping physicians connected with their OA patients during the COVID-19 pandemic, OA experts said in an interview.
“This is certainly relevant during the pandemic, but this has been of high interest for years as well, as researchers and clinicians have been seeking the best ways to reach patients with these types of programs,” said Kelli Allen, PhD, a research health scientist at the University of North Carolina at Chapel Hill.
Two separate studies evaluated the telemedicine platforms. In JAMA Internal Medicine, researchers reported that telephone-based cognitive-behavioral therapy (CBT) for patients aged 60 and older with OA and insomnia led to improved sleep, fatigue and, to a lesser extent, pain, in a randomized, controlled trial with 327 patients.
A separate randomized, controlled trial of 105 OA patients at the University of Nottingham (England), published in JAMA Network Open, reported that users of a smartphone-based exercise intervention app had greater improvements in pain and function than did controls.
“I think these two studies represent a first step in terms of moving forward, and certainly the interventions could be refined and potentially combined together for patients in the future,” said C. Kent Kwoh, MD, director of the University of Arizona Arthritis Center in Tucson.
Phone-based CBT study
The telephone-based CBT study consisted of two groups: the CBT group (n = 163) who completed six 20- to 30-minute telephone calls over 8 weeks, kept daily diaries, and received tailored educational materials and an education-only group (n = 164). At 2 months after treatment, Insomnia Severity Index scores decreased 8.1 points on average in the CBT group versus 4.8 points in the education-only patients (P < .001).
That variation between the intervention group and controls was sustained out to a year: 7.7 points lower than baseline versus 4.7 points lower. At the same time point, 56.3% of the CBT group remained in remission with Insomnia Severity Index scores less than 7 versus 25.8% of controls. Fatigue outcomes were similarly disparate between the groups.
Pain outcomes were a different story, however. “Post treatment, significant differences were observed for pain, but these differences were not sustained at 12-month follow-up,” first author Susan M. McCurry, PhD, a clinical psychologist and faculty member at the University of Washington, Seattle, and colleagues wrote.
“I think their positive findings illustrate that remotely delivered interventions can be ‘low tech’ and still effective,” Dr. Allen said of the CBT phone study. She noted that complete case data were available for 282 of 327 patients. “The high rate of session attendance suggests that they chose a delivery modality appropriate for their target patient group.”
The scalability of the telephone model is noteworthy, Dr. Kwoh said. “Having a telemedicine intervention that could be scaled a little more easily rather than an in-person intervention, and having individualized treatment, that’s beneficial, as is targeting two symptoms that are very bothersome and burdensome to patients with OA: insomnia and fatigue.” Following patients out to 12 months is a strength of the study, he added.
Smartphone app–based exercise study
The U.K. study evaluated 6-week outcomes of 48 patients with knee OA who used a proprietary app-based exercise program (Joint Academy) and 57 controls who used traditional self-management. The app provided daily exercises and texts, along with email and smartphone reminders. The app was derived from the Better Management of Patients with OA program initiated in Sweden in 2008 that used OA treatment guidelines for education and exercise in person in primary care clinics.
App users showed a 1.5-point reduction in numeric rating scale (NRS) pain score at 6 weeks versus virtually no change in controls (P < .001). In terms of secondary outcomes, pain scores improved 2.2 points on average for app users versus 1.2 for controls (P = .02), with similar improvements recorded in both stiffness and physical function.
Average change in the 30-second sit-to-stand test measured 4.5 for the app users and 1.2 for the usual-care group (P < .001). The study found no difference between the two groups in changes in temporal summation, conditional pain modulation, or Arthritis Research UK Musculoskeletal Health Questionnaire scores.
First author Sameer Akram Gohir, MSc, PhD, and colleagues wrote that the reasons for differences in outcomes between app users and controls aren’t clear. “The superior outcome in the intervention group may depend on the content and context in the app, including a combination of standardized exercises and information, as well as using a digital delivery system.”
Data gathering was cut short because of COVID-19 restrictions in the United Kingdom, as 27 patients missed their in-person follow-up visits. That was one shortcoming of the study, Dr. Kwoh noted.
“Given the caveats certainly they were able to show robust changes in terms of decreased pain, and also improvement in a variety of performance measures. Certainly this may be beneficial – we don’t know – in terms of cost-effectiveness, but it may be beneficial for insurance companies to adapt such a program,” he said, adding that future studies into the cost effectiveness of the digital platform would be in order.
“Certainly, if this program were to decrease physician visits or postpone the need for joint replacement for individuals, then it could be certainly very cost effective,” Dr. Kwoh said.
The completion rate among patients in the study – almost 90% – was “impressive,” Dr. Allen said. “However, this is a relatively short-term study, and I think an important question for future research is whether patients continue with this level of engagement for a longer period of time.”
Dr. McCurry had no relevant financial relationships to disclose. The CBT phone study received funding from the Public Health Service and the National Institute on Aging. Coauthors disclosed relationships with Campbell Alliance Group, Mapi Research Trust, and Pfizer. Dr. Gohir reported no relevant financial relationships. The study received funding from the Versus Arthritis UK Plan Center, the National Institute for Health Research Nottingham Biomedical Research Center, and Pfizer Global. The Joint Academy provided software for the study. A coauthor reported a financial relationships with Pfizer. Dr. Kwoh said that in the past year he has consulted for Express Scripts, Kolon Tissue Gene, LG Chem, and Regeneron. In the past year, he also received institutional grants for clinical trials from AbbVie, Cumberland, Eicos, Eli Lilly, GlaxoSmithKline, Mitsubishi, and Pfizer. Dr. Allen had no relevant financial relationships to disclose.
Remote interventions using an Internet-based app and telephone outreach to engage patients with osteoarthritis to self-manage their disease have demonstrated the potential to improve some symptoms, at least in the short term, showing the potential for tools to interact with OA patients without having them come into an office or clinic.
Remote interaction using these two forms of telemedicine – one a sophisticated digital platform, the other using a device that’s been around for almost 150 years – may have greater utility for keeping physicians connected with their OA patients during the COVID-19 pandemic, OA experts said in an interview.
“This is certainly relevant during the pandemic, but this has been of high interest for years as well, as researchers and clinicians have been seeking the best ways to reach patients with these types of programs,” said Kelli Allen, PhD, a research health scientist at the University of North Carolina at Chapel Hill.
Two separate studies evaluated the telemedicine platforms. In JAMA Internal Medicine, researchers reported that telephone-based cognitive-behavioral therapy (CBT) for patients aged 60 and older with OA and insomnia led to improved sleep, fatigue and, to a lesser extent, pain, in a randomized, controlled trial with 327 patients.
A separate randomized, controlled trial of 105 OA patients at the University of Nottingham (England), published in JAMA Network Open, reported that users of a smartphone-based exercise intervention app had greater improvements in pain and function than did controls.
“I think these two studies represent a first step in terms of moving forward, and certainly the interventions could be refined and potentially combined together for patients in the future,” said C. Kent Kwoh, MD, director of the University of Arizona Arthritis Center in Tucson.
Phone-based CBT study
The telephone-based CBT study consisted of two groups: the CBT group (n = 163) who completed six 20- to 30-minute telephone calls over 8 weeks, kept daily diaries, and received tailored educational materials and an education-only group (n = 164). At 2 months after treatment, Insomnia Severity Index scores decreased 8.1 points on average in the CBT group versus 4.8 points in the education-only patients (P < .001).
That variation between the intervention group and controls was sustained out to a year: 7.7 points lower than baseline versus 4.7 points lower. At the same time point, 56.3% of the CBT group remained in remission with Insomnia Severity Index scores less than 7 versus 25.8% of controls. Fatigue outcomes were similarly disparate between the groups.
Pain outcomes were a different story, however. “Post treatment, significant differences were observed for pain, but these differences were not sustained at 12-month follow-up,” first author Susan M. McCurry, PhD, a clinical psychologist and faculty member at the University of Washington, Seattle, and colleagues wrote.
“I think their positive findings illustrate that remotely delivered interventions can be ‘low tech’ and still effective,” Dr. Allen said of the CBT phone study. She noted that complete case data were available for 282 of 327 patients. “The high rate of session attendance suggests that they chose a delivery modality appropriate for their target patient group.”
The scalability of the telephone model is noteworthy, Dr. Kwoh said. “Having a telemedicine intervention that could be scaled a little more easily rather than an in-person intervention, and having individualized treatment, that’s beneficial, as is targeting two symptoms that are very bothersome and burdensome to patients with OA: insomnia and fatigue.” Following patients out to 12 months is a strength of the study, he added.
Smartphone app–based exercise study
The U.K. study evaluated 6-week outcomes of 48 patients with knee OA who used a proprietary app-based exercise program (Joint Academy) and 57 controls who used traditional self-management. The app provided daily exercises and texts, along with email and smartphone reminders. The app was derived from the Better Management of Patients with OA program initiated in Sweden in 2008 that used OA treatment guidelines for education and exercise in person in primary care clinics.
App users showed a 1.5-point reduction in numeric rating scale (NRS) pain score at 6 weeks versus virtually no change in controls (P < .001). In terms of secondary outcomes, pain scores improved 2.2 points on average for app users versus 1.2 for controls (P = .02), with similar improvements recorded in both stiffness and physical function.
Average change in the 30-second sit-to-stand test measured 4.5 for the app users and 1.2 for the usual-care group (P < .001). The study found no difference between the two groups in changes in temporal summation, conditional pain modulation, or Arthritis Research UK Musculoskeletal Health Questionnaire scores.
First author Sameer Akram Gohir, MSc, PhD, and colleagues wrote that the reasons for differences in outcomes between app users and controls aren’t clear. “The superior outcome in the intervention group may depend on the content and context in the app, including a combination of standardized exercises and information, as well as using a digital delivery system.”
Data gathering was cut short because of COVID-19 restrictions in the United Kingdom, as 27 patients missed their in-person follow-up visits. That was one shortcoming of the study, Dr. Kwoh noted.
“Given the caveats certainly they were able to show robust changes in terms of decreased pain, and also improvement in a variety of performance measures. Certainly this may be beneficial – we don’t know – in terms of cost-effectiveness, but it may be beneficial for insurance companies to adapt such a program,” he said, adding that future studies into the cost effectiveness of the digital platform would be in order.
“Certainly, if this program were to decrease physician visits or postpone the need for joint replacement for individuals, then it could be certainly very cost effective,” Dr. Kwoh said.
The completion rate among patients in the study – almost 90% – was “impressive,” Dr. Allen said. “However, this is a relatively short-term study, and I think an important question for future research is whether patients continue with this level of engagement for a longer period of time.”
Dr. McCurry had no relevant financial relationships to disclose. The CBT phone study received funding from the Public Health Service and the National Institute on Aging. Coauthors disclosed relationships with Campbell Alliance Group, Mapi Research Trust, and Pfizer. Dr. Gohir reported no relevant financial relationships. The study received funding from the Versus Arthritis UK Plan Center, the National Institute for Health Research Nottingham Biomedical Research Center, and Pfizer Global. The Joint Academy provided software for the study. A coauthor reported a financial relationships with Pfizer. Dr. Kwoh said that in the past year he has consulted for Express Scripts, Kolon Tissue Gene, LG Chem, and Regeneron. In the past year, he also received institutional grants for clinical trials from AbbVie, Cumberland, Eicos, Eli Lilly, GlaxoSmithKline, Mitsubishi, and Pfizer. Dr. Allen had no relevant financial relationships to disclose.
FROM JAMA INTERNAL MEDICINE AND JAMA NETWORK OPEN
OA risk-reduction program targets injured knees
A novel educational and personalized physical therapy program is showing signs that it may help people to mitigate their risk of developing knee osteoarthritis after an injury.
Speaking at the Canadian Arthritis Research Conference: Research with Impact, Jackie Whittaker, PhD, observed that initial work from the Stop Osteoarthritis (SOAR) program showed that meaningful improvements in knee-related quality of life and improvement in participants’ perceived self-management could be achieved.
Further feasibility work is ongoing and a proof-of-concept and phase 3 study need to follow, but the research suggests the approach could potentially help to reduce the substantial burden of managing people who develop posttraumatic OA (PTOA) of the knee.
Understanding the post–knee injury period
“Despite the progress that we’ve made in preventing injuries, and reducing disability in people with osteoarthritis, we lack good evidence about what should be done in the period between joint injury and the onset of osteoarthritis to delay or halt that onset,” Dr. Whittaker said at the virtual meeting, which was sponsored by the Arthritis Society, the Canadian Rheumatology Association, and Canada’s Institute of Musculoskeletal Health and Arthritis.
That’s where the SOAR program comes in. For the past 8 years, Dr. Whittaker, an assistant professor in the department of physical therapy at the University of British Columbia in Vancouver and affiliated to Arthritis Research Canada, and collaborators have been looking into the post–knee injury period with the aim of developing an intervention that could potentially reduce the risk of OA further down the line.
Much work has gone into understanding the burden and risk factors for PTOA of the knee in order to know who exactly to target with the intervention and what the risk factors may be for the subsequent development of OA .
This research suggests that knee injuries are most commonly seen in people aged between 15 and 35 years who participated in sporting or other physical activities, so this is the target population for the SOAR intervention.
Broadly speaking, sustaining any knee injury is associated with a sixfold increased risk for subsequent PTOA, Dr. Whittaker observed.
“Despite the fact that ACL [anterior cruciate ligament] and meniscal tears get all the press, collateral ligament injury are still associated with about a fivefold increased risk of osteoarthritis, and therefore maybe shouldn’t be so easily dismissed as an important target,” Dr. Whittaker said.
Postinjury risk factors for OA
“Basically, what all prevention comes down to is our understanding of risk factors and our ability to be able to modify them,” she said.
Previous joint injury is one of the strongest and most established modifiable risk factors for developing knee OA, and Dr. Whittaker and associates have performed two small but “mighty” cohort studies comparing people who have and have not had a knee injury. These two studies have looked at different time periods following injury to see if they could first identify the risk factors for developing OA some 3-10 years later, and then to look more closely at some of those risk factors in first 2 years after injury with a view to targeting these with an intervention.
Data analysis of the latter study is still ongoing but have shown that, among injured subjects, there is a fear of movement and reinjury, knee strength is weaker in both injured and uninjured knees, and they are perhaps less physically active than those who have not been injured.
“Going into those two studies, we knew that this group of people already [had an] increased risk for osteoarthritis because they had an injury. However, what we found is that it looks like this risk may be compounded through adiposity [and] deficits in muscle strength and physical inactivity, which are associated with pain, stiffness, lack of confidence, and at times, unrealistic expectations and poor pacing,” Dr. Whittaker said.
She added: “It also looks like some of these additional factors and particular adiposity or fat gain may develop after injury, which would then give us a concrete target for delaying or halting the onset of osteoarthritis in the segment of the population.”
SOAR program components
The SOAR program intervention is an 8-week, physiotherapist-led program that targets people aged 15-35 years who have had a sport-related knee injury and received formal care. All of this is conducted via videoconferencing software and starts off with a 2-hour group education session or “knee camp.” This is followed by a one-on-one assessment with a physiotherapist and setting exercise and physical activity goals for the week.
Participants then undertake their personalized exercise and physical activity programs at home and track their progress using an activity monitor. They can participate in an optional weekly group exercise class and receive weekly one-on-one physiotherapy counseling where goals can be modified and any issues participants might be experiencing solved.
According to Dr. Whittaker, “this program really aims to increase participants capacity to manage their elevated risk for osteoarthritis, and we’re doing this by also optimizing their knee muscle function and their physical activity participation.”
While the knee camp enables a therapeutic alliance to be formed between participants and their physiotherapists, the weekly group classes provide social support and an opportunity to interact with others.
“Brief action planning builds self-efficacy [and] promotes autonomous health behaviors, while goal setting and tracking provide accountability, feedback about progress, and facilitated adherence,” she said.
And finally, regular communication with a physiotherapist in the program ensures timely support to learn how to navigate obstacles and helps participants to learn how to deal with their own knee health.
Testing the feasibility of the SOAR program intervention
“Currently we are smack in the middle of our feasibility study,” Dr. Whittaker said. So far, four physiotherapists have been trained to deliver an abridged, 4-week version of the program, and 25 of a planned 30 participants have been enrolled.
Results seem promising so far. No participants have dropped out of the program to date and attendance is at 100%.
“Based on data from the first 12 participants who completed the program, we are meeting all of our ‘a priori’ program benchmarks,” Dr. Whittaker said.
“It is very early days,” she emphasized, but “we are excited to see clinically important improvements in both knee-related quality of life and perceived self-management.
“This gives us some confidence that maybe all this time that we’ve put into developing our intervention is paying off, but obviously time will tell if we’re headed in the right direction,” she said. “Perhaps in time, we may be able to look at whether or not the individuals that participated in that program have fewer symptoms of OA disease. But that will obviously take us a few years before we’ll be able to get to that point.”
Dr. Whittaker acknowledged receiving funding for the SOAR program from the Arthritis Society, the Michael Smith Foundation for Health Research, BC SUPPORT Unit, and the Canadian Musculoskeletal Rehab Network.
A novel educational and personalized physical therapy program is showing signs that it may help people to mitigate their risk of developing knee osteoarthritis after an injury.
Speaking at the Canadian Arthritis Research Conference: Research with Impact, Jackie Whittaker, PhD, observed that initial work from the Stop Osteoarthritis (SOAR) program showed that meaningful improvements in knee-related quality of life and improvement in participants’ perceived self-management could be achieved.
Further feasibility work is ongoing and a proof-of-concept and phase 3 study need to follow, but the research suggests the approach could potentially help to reduce the substantial burden of managing people who develop posttraumatic OA (PTOA) of the knee.
Understanding the post–knee injury period
“Despite the progress that we’ve made in preventing injuries, and reducing disability in people with osteoarthritis, we lack good evidence about what should be done in the period between joint injury and the onset of osteoarthritis to delay or halt that onset,” Dr. Whittaker said at the virtual meeting, which was sponsored by the Arthritis Society, the Canadian Rheumatology Association, and Canada’s Institute of Musculoskeletal Health and Arthritis.
That’s where the SOAR program comes in. For the past 8 years, Dr. Whittaker, an assistant professor in the department of physical therapy at the University of British Columbia in Vancouver and affiliated to Arthritis Research Canada, and collaborators have been looking into the post–knee injury period with the aim of developing an intervention that could potentially reduce the risk of OA further down the line.
Much work has gone into understanding the burden and risk factors for PTOA of the knee in order to know who exactly to target with the intervention and what the risk factors may be for the subsequent development of OA .
This research suggests that knee injuries are most commonly seen in people aged between 15 and 35 years who participated in sporting or other physical activities, so this is the target population for the SOAR intervention.
Broadly speaking, sustaining any knee injury is associated with a sixfold increased risk for subsequent PTOA, Dr. Whittaker observed.
“Despite the fact that ACL [anterior cruciate ligament] and meniscal tears get all the press, collateral ligament injury are still associated with about a fivefold increased risk of osteoarthritis, and therefore maybe shouldn’t be so easily dismissed as an important target,” Dr. Whittaker said.
Postinjury risk factors for OA
“Basically, what all prevention comes down to is our understanding of risk factors and our ability to be able to modify them,” she said.
Previous joint injury is one of the strongest and most established modifiable risk factors for developing knee OA, and Dr. Whittaker and associates have performed two small but “mighty” cohort studies comparing people who have and have not had a knee injury. These two studies have looked at different time periods following injury to see if they could first identify the risk factors for developing OA some 3-10 years later, and then to look more closely at some of those risk factors in first 2 years after injury with a view to targeting these with an intervention.
Data analysis of the latter study is still ongoing but have shown that, among injured subjects, there is a fear of movement and reinjury, knee strength is weaker in both injured and uninjured knees, and they are perhaps less physically active than those who have not been injured.
“Going into those two studies, we knew that this group of people already [had an] increased risk for osteoarthritis because they had an injury. However, what we found is that it looks like this risk may be compounded through adiposity [and] deficits in muscle strength and physical inactivity, which are associated with pain, stiffness, lack of confidence, and at times, unrealistic expectations and poor pacing,” Dr. Whittaker said.
She added: “It also looks like some of these additional factors and particular adiposity or fat gain may develop after injury, which would then give us a concrete target for delaying or halting the onset of osteoarthritis in the segment of the population.”
SOAR program components
The SOAR program intervention is an 8-week, physiotherapist-led program that targets people aged 15-35 years who have had a sport-related knee injury and received formal care. All of this is conducted via videoconferencing software and starts off with a 2-hour group education session or “knee camp.” This is followed by a one-on-one assessment with a physiotherapist and setting exercise and physical activity goals for the week.
Participants then undertake their personalized exercise and physical activity programs at home and track their progress using an activity monitor. They can participate in an optional weekly group exercise class and receive weekly one-on-one physiotherapy counseling where goals can be modified and any issues participants might be experiencing solved.
According to Dr. Whittaker, “this program really aims to increase participants capacity to manage their elevated risk for osteoarthritis, and we’re doing this by also optimizing their knee muscle function and their physical activity participation.”
While the knee camp enables a therapeutic alliance to be formed between participants and their physiotherapists, the weekly group classes provide social support and an opportunity to interact with others.
“Brief action planning builds self-efficacy [and] promotes autonomous health behaviors, while goal setting and tracking provide accountability, feedback about progress, and facilitated adherence,” she said.
And finally, regular communication with a physiotherapist in the program ensures timely support to learn how to navigate obstacles and helps participants to learn how to deal with their own knee health.
Testing the feasibility of the SOAR program intervention
“Currently we are smack in the middle of our feasibility study,” Dr. Whittaker said. So far, four physiotherapists have been trained to deliver an abridged, 4-week version of the program, and 25 of a planned 30 participants have been enrolled.
Results seem promising so far. No participants have dropped out of the program to date and attendance is at 100%.
“Based on data from the first 12 participants who completed the program, we are meeting all of our ‘a priori’ program benchmarks,” Dr. Whittaker said.
“It is very early days,” she emphasized, but “we are excited to see clinically important improvements in both knee-related quality of life and perceived self-management.
“This gives us some confidence that maybe all this time that we’ve put into developing our intervention is paying off, but obviously time will tell if we’re headed in the right direction,” she said. “Perhaps in time, we may be able to look at whether or not the individuals that participated in that program have fewer symptoms of OA disease. But that will obviously take us a few years before we’ll be able to get to that point.”
Dr. Whittaker acknowledged receiving funding for the SOAR program from the Arthritis Society, the Michael Smith Foundation for Health Research, BC SUPPORT Unit, and the Canadian Musculoskeletal Rehab Network.
A novel educational and personalized physical therapy program is showing signs that it may help people to mitigate their risk of developing knee osteoarthritis after an injury.
Speaking at the Canadian Arthritis Research Conference: Research with Impact, Jackie Whittaker, PhD, observed that initial work from the Stop Osteoarthritis (SOAR) program showed that meaningful improvements in knee-related quality of life and improvement in participants’ perceived self-management could be achieved.
Further feasibility work is ongoing and a proof-of-concept and phase 3 study need to follow, but the research suggests the approach could potentially help to reduce the substantial burden of managing people who develop posttraumatic OA (PTOA) of the knee.
Understanding the post–knee injury period
“Despite the progress that we’ve made in preventing injuries, and reducing disability in people with osteoarthritis, we lack good evidence about what should be done in the period between joint injury and the onset of osteoarthritis to delay or halt that onset,” Dr. Whittaker said at the virtual meeting, which was sponsored by the Arthritis Society, the Canadian Rheumatology Association, and Canada’s Institute of Musculoskeletal Health and Arthritis.
That’s where the SOAR program comes in. For the past 8 years, Dr. Whittaker, an assistant professor in the department of physical therapy at the University of British Columbia in Vancouver and affiliated to Arthritis Research Canada, and collaborators have been looking into the post–knee injury period with the aim of developing an intervention that could potentially reduce the risk of OA further down the line.
Much work has gone into understanding the burden and risk factors for PTOA of the knee in order to know who exactly to target with the intervention and what the risk factors may be for the subsequent development of OA .
This research suggests that knee injuries are most commonly seen in people aged between 15 and 35 years who participated in sporting or other physical activities, so this is the target population for the SOAR intervention.
Broadly speaking, sustaining any knee injury is associated with a sixfold increased risk for subsequent PTOA, Dr. Whittaker observed.
“Despite the fact that ACL [anterior cruciate ligament] and meniscal tears get all the press, collateral ligament injury are still associated with about a fivefold increased risk of osteoarthritis, and therefore maybe shouldn’t be so easily dismissed as an important target,” Dr. Whittaker said.
Postinjury risk factors for OA
“Basically, what all prevention comes down to is our understanding of risk factors and our ability to be able to modify them,” she said.
Previous joint injury is one of the strongest and most established modifiable risk factors for developing knee OA, and Dr. Whittaker and associates have performed two small but “mighty” cohort studies comparing people who have and have not had a knee injury. These two studies have looked at different time periods following injury to see if they could first identify the risk factors for developing OA some 3-10 years later, and then to look more closely at some of those risk factors in first 2 years after injury with a view to targeting these with an intervention.
Data analysis of the latter study is still ongoing but have shown that, among injured subjects, there is a fear of movement and reinjury, knee strength is weaker in both injured and uninjured knees, and they are perhaps less physically active than those who have not been injured.
“Going into those two studies, we knew that this group of people already [had an] increased risk for osteoarthritis because they had an injury. However, what we found is that it looks like this risk may be compounded through adiposity [and] deficits in muscle strength and physical inactivity, which are associated with pain, stiffness, lack of confidence, and at times, unrealistic expectations and poor pacing,” Dr. Whittaker said.
She added: “It also looks like some of these additional factors and particular adiposity or fat gain may develop after injury, which would then give us a concrete target for delaying or halting the onset of osteoarthritis in the segment of the population.”
SOAR program components
The SOAR program intervention is an 8-week, physiotherapist-led program that targets people aged 15-35 years who have had a sport-related knee injury and received formal care. All of this is conducted via videoconferencing software and starts off with a 2-hour group education session or “knee camp.” This is followed by a one-on-one assessment with a physiotherapist and setting exercise and physical activity goals for the week.
Participants then undertake their personalized exercise and physical activity programs at home and track their progress using an activity monitor. They can participate in an optional weekly group exercise class and receive weekly one-on-one physiotherapy counseling where goals can be modified and any issues participants might be experiencing solved.
According to Dr. Whittaker, “this program really aims to increase participants capacity to manage their elevated risk for osteoarthritis, and we’re doing this by also optimizing their knee muscle function and their physical activity participation.”
While the knee camp enables a therapeutic alliance to be formed between participants and their physiotherapists, the weekly group classes provide social support and an opportunity to interact with others.
“Brief action planning builds self-efficacy [and] promotes autonomous health behaviors, while goal setting and tracking provide accountability, feedback about progress, and facilitated adherence,” she said.
And finally, regular communication with a physiotherapist in the program ensures timely support to learn how to navigate obstacles and helps participants to learn how to deal with their own knee health.
Testing the feasibility of the SOAR program intervention
“Currently we are smack in the middle of our feasibility study,” Dr. Whittaker said. So far, four physiotherapists have been trained to deliver an abridged, 4-week version of the program, and 25 of a planned 30 participants have been enrolled.
Results seem promising so far. No participants have dropped out of the program to date and attendance is at 100%.
“Based on data from the first 12 participants who completed the program, we are meeting all of our ‘a priori’ program benchmarks,” Dr. Whittaker said.
“It is very early days,” she emphasized, but “we are excited to see clinically important improvements in both knee-related quality of life and perceived self-management.
“This gives us some confidence that maybe all this time that we’ve put into developing our intervention is paying off, but obviously time will tell if we’re headed in the right direction,” she said. “Perhaps in time, we may be able to look at whether or not the individuals that participated in that program have fewer symptoms of OA disease. But that will obviously take us a few years before we’ll be able to get to that point.”
Dr. Whittaker acknowledged receiving funding for the SOAR program from the Arthritis Society, the Michael Smith Foundation for Health Research, BC SUPPORT Unit, and the Canadian Musculoskeletal Rehab Network.
FROM CARC 2021
COVID-19 vaccination recommended for rheumatology patients
People with rheumatic diseases should get vaccinated against SARS-CoV-2 as soon as possible, the American College of Rheumatology (ACR) recommends.
“It may be that people with rheumatic diseases are at increased risk of developing COVID or serious COVID-related complications,” Jonathan Hausmann, MD, assistant professor of medicine at Harvard Medical School, Boston, said in an ACR podcast. “So the need to prevent COVID-19 is incredibly important in this group of patients.”
The guidelines recommend a delay in vaccination only in rare circumstances, such as for patients with very severe illness or who have recently been administered rituximab, Jeffrey R. Curtis, MD, MPH, lead author of the guidelines, said in the podcast.
“Our members have been inundated with questions and concerns from their patients on whether they should receive the vaccine,” ACR President David Karp, MD, PhD, said in a press release.
So the ACR convened a panel of nine rheumatologists, two infectious disease specialists, and two public health experts. Over the course of 8 weeks, the task force reviewed the literature and agreed on recommendations. The organization posted a summary of the guidelines on its website after its board of directors approved it Feb. 8. The paper is pending journal peer review.
Some risks are real
The task force confined its research to the COVID-19 vaccines being offered by Pfizer and Moderna because they are currently the only ones approved by the Food and Drug Administration. It found no reason to distinguish between the two vaccines in its recommendations.
Because little research has directly addressed the question concerning COVID-19 vaccination for patients with rheumatic diseases, the task force extrapolated from data on other vaccinations in people with rheumatic disease and on the COVID-19 vaccinations in other populations.
It analyzed reports that other types of vaccination, such as for influenza, triggered flares of rheumatic conditions. “It is really individual case reports or small cohorts where there may be a somewhat higher incidence of flare, but it’s usually not very large in its magnitude nor duration,” said Dr. Curtis of the University of Alabama at Birmingham.
The task force also considered the possibility that vaccinations could lead to a new autoimmune disorder, such as Guillain-Barré syndrome or Bell palsy. The risk is real, the task force decided, but not significant enough to influence their recommendations.
Likewise, in immunocompromised people, vaccinations with live virus, such as those for shingles, might trigger the infection the vaccination is meant to prevent. But this can’t happen with the Pfizer and Moderna COVID-19 vaccines because they contain messenger RNA instead of live viruses, Dr. Curtis said.
Although it might be optimal to administer the vaccines when rheumatic diseases are quiescent, the urgency of getting vaccinated overrides that consideration, Dr. Curtis said. “By and large, there was a general consensus to not want to delay vaccination until somebody was stable and doing great, because you don’t know how long that’s going to be,” he said.
How well does it work?
One unanswered question is whether the COVID-19 vaccines work as well for patients with rheumatic diseases. The task force was reassured by data showing efficacy across a range of subgroups, including some with immunosenescence, Dr. Curtis said. “But until we have data in rheumatology patients, we’re just not going to know,” he said.
The guidelines specify that some drug regimens be modified when patients are vaccinated.
For patients taking rituximab, vaccination should be delayed, but only for those who are able to maintain safe social distancing to reduce the risk for COVID-19 exposure, Dr. Curtis said. “If somebody has just gotten rituximab recently, it might be more ideal to complete the vaccine series about 2-4 weeks before the next rituximab dose,” he said. “So if you are giving that therapy, say, at 6-month intervals, if you could vaccinate them at around month 5 from the most recent rituximab cycle, that might be more ideal.”
The guidance calls for withholding JAK inhibitors for a week after each vaccine dose is administered.
It calls for holding SQ abatacept 1 week prior and 1 week after the first COVID-19 vaccine dose, with no interruption after the second dose.
For abatacept IV, clinicians should “time vaccine administration so that the first vaccination will occur 4 weeks after abatacept infusion (i.e., the entire dosing interval), and postpone the subsequent abatacept infusion by 1 week (i.e., a 5-week gap in total).” It recommends no medication adjustment for the second vaccine dose.
For cyclophosphamide, the guidance recommends timing administration to occur about a week after each vaccine dose, when feasible.
None of this advice should supersede clinical judgment, Dr. Curtis said.
A version of this article first appeared on Medscape.com.
People with rheumatic diseases should get vaccinated against SARS-CoV-2 as soon as possible, the American College of Rheumatology (ACR) recommends.
“It may be that people with rheumatic diseases are at increased risk of developing COVID or serious COVID-related complications,” Jonathan Hausmann, MD, assistant professor of medicine at Harvard Medical School, Boston, said in an ACR podcast. “So the need to prevent COVID-19 is incredibly important in this group of patients.”
The guidelines recommend a delay in vaccination only in rare circumstances, such as for patients with very severe illness or who have recently been administered rituximab, Jeffrey R. Curtis, MD, MPH, lead author of the guidelines, said in the podcast.
“Our members have been inundated with questions and concerns from their patients on whether they should receive the vaccine,” ACR President David Karp, MD, PhD, said in a press release.
So the ACR convened a panel of nine rheumatologists, two infectious disease specialists, and two public health experts. Over the course of 8 weeks, the task force reviewed the literature and agreed on recommendations. The organization posted a summary of the guidelines on its website after its board of directors approved it Feb. 8. The paper is pending journal peer review.
Some risks are real
The task force confined its research to the COVID-19 vaccines being offered by Pfizer and Moderna because they are currently the only ones approved by the Food and Drug Administration. It found no reason to distinguish between the two vaccines in its recommendations.
Because little research has directly addressed the question concerning COVID-19 vaccination for patients with rheumatic diseases, the task force extrapolated from data on other vaccinations in people with rheumatic disease and on the COVID-19 vaccinations in other populations.
It analyzed reports that other types of vaccination, such as for influenza, triggered flares of rheumatic conditions. “It is really individual case reports or small cohorts where there may be a somewhat higher incidence of flare, but it’s usually not very large in its magnitude nor duration,” said Dr. Curtis of the University of Alabama at Birmingham.
The task force also considered the possibility that vaccinations could lead to a new autoimmune disorder, such as Guillain-Barré syndrome or Bell palsy. The risk is real, the task force decided, but not significant enough to influence their recommendations.
Likewise, in immunocompromised people, vaccinations with live virus, such as those for shingles, might trigger the infection the vaccination is meant to prevent. But this can’t happen with the Pfizer and Moderna COVID-19 vaccines because they contain messenger RNA instead of live viruses, Dr. Curtis said.
Although it might be optimal to administer the vaccines when rheumatic diseases are quiescent, the urgency of getting vaccinated overrides that consideration, Dr. Curtis said. “By and large, there was a general consensus to not want to delay vaccination until somebody was stable and doing great, because you don’t know how long that’s going to be,” he said.
How well does it work?
One unanswered question is whether the COVID-19 vaccines work as well for patients with rheumatic diseases. The task force was reassured by data showing efficacy across a range of subgroups, including some with immunosenescence, Dr. Curtis said. “But until we have data in rheumatology patients, we’re just not going to know,” he said.
The guidelines specify that some drug regimens be modified when patients are vaccinated.
For patients taking rituximab, vaccination should be delayed, but only for those who are able to maintain safe social distancing to reduce the risk for COVID-19 exposure, Dr. Curtis said. “If somebody has just gotten rituximab recently, it might be more ideal to complete the vaccine series about 2-4 weeks before the next rituximab dose,” he said. “So if you are giving that therapy, say, at 6-month intervals, if you could vaccinate them at around month 5 from the most recent rituximab cycle, that might be more ideal.”
The guidance calls for withholding JAK inhibitors for a week after each vaccine dose is administered.
It calls for holding SQ abatacept 1 week prior and 1 week after the first COVID-19 vaccine dose, with no interruption after the second dose.
For abatacept IV, clinicians should “time vaccine administration so that the first vaccination will occur 4 weeks after abatacept infusion (i.e., the entire dosing interval), and postpone the subsequent abatacept infusion by 1 week (i.e., a 5-week gap in total).” It recommends no medication adjustment for the second vaccine dose.
For cyclophosphamide, the guidance recommends timing administration to occur about a week after each vaccine dose, when feasible.
None of this advice should supersede clinical judgment, Dr. Curtis said.
A version of this article first appeared on Medscape.com.
People with rheumatic diseases should get vaccinated against SARS-CoV-2 as soon as possible, the American College of Rheumatology (ACR) recommends.
“It may be that people with rheumatic diseases are at increased risk of developing COVID or serious COVID-related complications,” Jonathan Hausmann, MD, assistant professor of medicine at Harvard Medical School, Boston, said in an ACR podcast. “So the need to prevent COVID-19 is incredibly important in this group of patients.”
The guidelines recommend a delay in vaccination only in rare circumstances, such as for patients with very severe illness or who have recently been administered rituximab, Jeffrey R. Curtis, MD, MPH, lead author of the guidelines, said in the podcast.
“Our members have been inundated with questions and concerns from their patients on whether they should receive the vaccine,” ACR President David Karp, MD, PhD, said in a press release.
So the ACR convened a panel of nine rheumatologists, two infectious disease specialists, and two public health experts. Over the course of 8 weeks, the task force reviewed the literature and agreed on recommendations. The organization posted a summary of the guidelines on its website after its board of directors approved it Feb. 8. The paper is pending journal peer review.
Some risks are real
The task force confined its research to the COVID-19 vaccines being offered by Pfizer and Moderna because they are currently the only ones approved by the Food and Drug Administration. It found no reason to distinguish between the two vaccines in its recommendations.
Because little research has directly addressed the question concerning COVID-19 vaccination for patients with rheumatic diseases, the task force extrapolated from data on other vaccinations in people with rheumatic disease and on the COVID-19 vaccinations in other populations.
It analyzed reports that other types of vaccination, such as for influenza, triggered flares of rheumatic conditions. “It is really individual case reports or small cohorts where there may be a somewhat higher incidence of flare, but it’s usually not very large in its magnitude nor duration,” said Dr. Curtis of the University of Alabama at Birmingham.
The task force also considered the possibility that vaccinations could lead to a new autoimmune disorder, such as Guillain-Barré syndrome or Bell palsy. The risk is real, the task force decided, but not significant enough to influence their recommendations.
Likewise, in immunocompromised people, vaccinations with live virus, such as those for shingles, might trigger the infection the vaccination is meant to prevent. But this can’t happen with the Pfizer and Moderna COVID-19 vaccines because they contain messenger RNA instead of live viruses, Dr. Curtis said.
Although it might be optimal to administer the vaccines when rheumatic diseases are quiescent, the urgency of getting vaccinated overrides that consideration, Dr. Curtis said. “By and large, there was a general consensus to not want to delay vaccination until somebody was stable and doing great, because you don’t know how long that’s going to be,” he said.
How well does it work?
One unanswered question is whether the COVID-19 vaccines work as well for patients with rheumatic diseases. The task force was reassured by data showing efficacy across a range of subgroups, including some with immunosenescence, Dr. Curtis said. “But until we have data in rheumatology patients, we’re just not going to know,” he said.
The guidelines specify that some drug regimens be modified when patients are vaccinated.
For patients taking rituximab, vaccination should be delayed, but only for those who are able to maintain safe social distancing to reduce the risk for COVID-19 exposure, Dr. Curtis said. “If somebody has just gotten rituximab recently, it might be more ideal to complete the vaccine series about 2-4 weeks before the next rituximab dose,” he said. “So if you are giving that therapy, say, at 6-month intervals, if you could vaccinate them at around month 5 from the most recent rituximab cycle, that might be more ideal.”
The guidance calls for withholding JAK inhibitors for a week after each vaccine dose is administered.
It calls for holding SQ abatacept 1 week prior and 1 week after the first COVID-19 vaccine dose, with no interruption after the second dose.
For abatacept IV, clinicians should “time vaccine administration so that the first vaccination will occur 4 weeks after abatacept infusion (i.e., the entire dosing interval), and postpone the subsequent abatacept infusion by 1 week (i.e., a 5-week gap in total).” It recommends no medication adjustment for the second vaccine dose.
For cyclophosphamide, the guidance recommends timing administration to occur about a week after each vaccine dose, when feasible.
None of this advice should supersede clinical judgment, Dr. Curtis said.
A version of this article first appeared on Medscape.com.
PCPs play a small part in low-value care spending
according to a brief report published online Jan. 18 in Annals of Internal Medicine.
However, one expert said there are better ways to curb low-value care than focusing on which specialties are guilty of the practice.
Analyzing a 20% random sample of Medicare Part B claims, Aaron Baum, PhD, with the Icahn School of Medicine at Mount Sinai, New York, and colleagues found that the services primary care physicians performed or ordered made up on average 8.3% of the low-value care their patients received (interquartile range, 3.9%-15.1%; 95th percentile, 35.6%) and their referrals made up 15.4% (IQR, 6.3%-26.4%; 95th percentile, 44.6%).
By specialty, cardiology had the worst record with 27% of all spending on low-value services ($1.8 billion) attributed to that specialty. Yet, of the 25 highest-spending specialties in the report, 12 of them were associated with 1% or less than 1% each of all low-value spending, indicating the waste was widely distributed.
Dr. Baum said in an interview that though there are some PCPs guilty of high spending on low-value services, overall, most primary care physicians’ low-value services add up to only 0.3% of Part B spending. He noted that Part B spending is about one-third of all Medicare spending.
Primary care is often thought to be at the core of care management and spending and PCPs are often seen as the gatekeepers, but this analysis suggests that efforts to make big differences in curtailing low-value spending might be more effective elsewhere.
“There’s only so much spending you can reduce by changing primary care physicians’ services that they directly perform,” Dr. Baum said.
Low-value care is costly, can be harmful
Mark Fendrick, MD, director of the University of Michigan’s Center for Value-Based Insurance Design in Ann Arbor, said in an interview that the report adds confirmation to previous research that has consistently shown low-value care is “extremely common, very costly, and provided by primary care providers and specialists alike.” He noted that it can also be harmful.
“The math is simple,” he said. “If we want to improve coverage and lower patient costs for essential services like visits, diagnostic tests, and drugs, we have to reduce spending on those services that do not make Americans any healthier.”
The study ranked 31 clinical services judged to be low value by physician societies, Medicare and clinical guidelines, and their use among beneficiaries enrolled between 2007 and 2014. Here’s how the top six low-value services compare.
Dr. Fendrick said a weakness of the paper is the years of the data (2007-2014). Some of the criteria around low-value care have changed since then. The age that a prostate-specific antigen test becomes low-value is now 70 years, for instance, instead of 75. He added that some of the figures attributed to non-PCP providers appear out of date.
Dr. Fendrick said, “I understand that there are Medicare patients who end up at a gastroenterologist or surgeon’s office to get colorectal cancer screening, but it would be very hard for me to believe that half of stress tests and over half of colon cancer screening over [age] 85 [years] and half of PSA for people over 75 did not have some type of referring clinicians involved. I certainly don’t think that would be the case in 2020-2021.”
Dr. Baum said those years were the latest years available for the data points needed for this analysis, but he and his colleagues were working to update the data for future publication.
Dr. Fendrick said not much has changed in recent years in terms of waste on low-value care, even with campaigns such as Choosing Wisely dedicated to identifying low-value services or procedures in each specialty.
“I believe there’s not a particular group of clinicians one way or the other who are actually doing any better now than they were 7 years ago,” he said. He would rather focus less on which specialties are associated with the most low-value care and more on the underlying policies that encourage low-value care.
“If you’re going to get paid for doing a stress test and get paid nothing or significantly less if you don’t, the incentives are in the wrong direction,” he said.
Dr. Fendrick said the pandemic era provides an opportunity to eliminate low-value care because use of those services has dropped drastically as resources have been diverted to COVID-19 patients and many services have been delayed or canceled.
He said he has been pushing an approach that providers should be paid more after the pandemic “to do the things we want them to do.”
As an example, he said, instead of paying $886 million on colonoscopies for people over the age of 85, “why don’t we put a policy in place that would make it better for patients by lowering cost sharing and better for providers by paying them more to do the service on the people who need it as opposed to the people who don’t?”
The research was funded by the American Board of Family Medicine Foundation. Dr. Baum and a coauthor reported receiving personal fees from American Board of Family Medicine Foundation during the conduct of the study. Another coauthor reported receiving personal fees from Collective Health, HealthRight 360, PLOS Medicine, and the New England Journal of Medicine, outside the submitted work. Dr. Fendrick disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to a brief report published online Jan. 18 in Annals of Internal Medicine.
However, one expert said there are better ways to curb low-value care than focusing on which specialties are guilty of the practice.
Analyzing a 20% random sample of Medicare Part B claims, Aaron Baum, PhD, with the Icahn School of Medicine at Mount Sinai, New York, and colleagues found that the services primary care physicians performed or ordered made up on average 8.3% of the low-value care their patients received (interquartile range, 3.9%-15.1%; 95th percentile, 35.6%) and their referrals made up 15.4% (IQR, 6.3%-26.4%; 95th percentile, 44.6%).
By specialty, cardiology had the worst record with 27% of all spending on low-value services ($1.8 billion) attributed to that specialty. Yet, of the 25 highest-spending specialties in the report, 12 of them were associated with 1% or less than 1% each of all low-value spending, indicating the waste was widely distributed.
Dr. Baum said in an interview that though there are some PCPs guilty of high spending on low-value services, overall, most primary care physicians’ low-value services add up to only 0.3% of Part B spending. He noted that Part B spending is about one-third of all Medicare spending.
Primary care is often thought to be at the core of care management and spending and PCPs are often seen as the gatekeepers, but this analysis suggests that efforts to make big differences in curtailing low-value spending might be more effective elsewhere.
“There’s only so much spending you can reduce by changing primary care physicians’ services that they directly perform,” Dr. Baum said.
Low-value care is costly, can be harmful
Mark Fendrick, MD, director of the University of Michigan’s Center for Value-Based Insurance Design in Ann Arbor, said in an interview that the report adds confirmation to previous research that has consistently shown low-value care is “extremely common, very costly, and provided by primary care providers and specialists alike.” He noted that it can also be harmful.
“The math is simple,” he said. “If we want to improve coverage and lower patient costs for essential services like visits, diagnostic tests, and drugs, we have to reduce spending on those services that do not make Americans any healthier.”
The study ranked 31 clinical services judged to be low value by physician societies, Medicare and clinical guidelines, and their use among beneficiaries enrolled between 2007 and 2014. Here’s how the top six low-value services compare.
Dr. Fendrick said a weakness of the paper is the years of the data (2007-2014). Some of the criteria around low-value care have changed since then. The age that a prostate-specific antigen test becomes low-value is now 70 years, for instance, instead of 75. He added that some of the figures attributed to non-PCP providers appear out of date.
Dr. Fendrick said, “I understand that there are Medicare patients who end up at a gastroenterologist or surgeon’s office to get colorectal cancer screening, but it would be very hard for me to believe that half of stress tests and over half of colon cancer screening over [age] 85 [years] and half of PSA for people over 75 did not have some type of referring clinicians involved. I certainly don’t think that would be the case in 2020-2021.”
Dr. Baum said those years were the latest years available for the data points needed for this analysis, but he and his colleagues were working to update the data for future publication.
Dr. Fendrick said not much has changed in recent years in terms of waste on low-value care, even with campaigns such as Choosing Wisely dedicated to identifying low-value services or procedures in each specialty.
“I believe there’s not a particular group of clinicians one way or the other who are actually doing any better now than they were 7 years ago,” he said. He would rather focus less on which specialties are associated with the most low-value care and more on the underlying policies that encourage low-value care.
“If you’re going to get paid for doing a stress test and get paid nothing or significantly less if you don’t, the incentives are in the wrong direction,” he said.
Dr. Fendrick said the pandemic era provides an opportunity to eliminate low-value care because use of those services has dropped drastically as resources have been diverted to COVID-19 patients and many services have been delayed or canceled.
He said he has been pushing an approach that providers should be paid more after the pandemic “to do the things we want them to do.”
As an example, he said, instead of paying $886 million on colonoscopies for people over the age of 85, “why don’t we put a policy in place that would make it better for patients by lowering cost sharing and better for providers by paying them more to do the service on the people who need it as opposed to the people who don’t?”
The research was funded by the American Board of Family Medicine Foundation. Dr. Baum and a coauthor reported receiving personal fees from American Board of Family Medicine Foundation during the conduct of the study. Another coauthor reported receiving personal fees from Collective Health, HealthRight 360, PLOS Medicine, and the New England Journal of Medicine, outside the submitted work. Dr. Fendrick disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to a brief report published online Jan. 18 in Annals of Internal Medicine.
However, one expert said there are better ways to curb low-value care than focusing on which specialties are guilty of the practice.
Analyzing a 20% random sample of Medicare Part B claims, Aaron Baum, PhD, with the Icahn School of Medicine at Mount Sinai, New York, and colleagues found that the services primary care physicians performed or ordered made up on average 8.3% of the low-value care their patients received (interquartile range, 3.9%-15.1%; 95th percentile, 35.6%) and their referrals made up 15.4% (IQR, 6.3%-26.4%; 95th percentile, 44.6%).
By specialty, cardiology had the worst record with 27% of all spending on low-value services ($1.8 billion) attributed to that specialty. Yet, of the 25 highest-spending specialties in the report, 12 of them were associated with 1% or less than 1% each of all low-value spending, indicating the waste was widely distributed.
Dr. Baum said in an interview that though there are some PCPs guilty of high spending on low-value services, overall, most primary care physicians’ low-value services add up to only 0.3% of Part B spending. He noted that Part B spending is about one-third of all Medicare spending.
Primary care is often thought to be at the core of care management and spending and PCPs are often seen as the gatekeepers, but this analysis suggests that efforts to make big differences in curtailing low-value spending might be more effective elsewhere.
“There’s only so much spending you can reduce by changing primary care physicians’ services that they directly perform,” Dr. Baum said.
Low-value care is costly, can be harmful
Mark Fendrick, MD, director of the University of Michigan’s Center for Value-Based Insurance Design in Ann Arbor, said in an interview that the report adds confirmation to previous research that has consistently shown low-value care is “extremely common, very costly, and provided by primary care providers and specialists alike.” He noted that it can also be harmful.
“The math is simple,” he said. “If we want to improve coverage and lower patient costs for essential services like visits, diagnostic tests, and drugs, we have to reduce spending on those services that do not make Americans any healthier.”
The study ranked 31 clinical services judged to be low value by physician societies, Medicare and clinical guidelines, and their use among beneficiaries enrolled between 2007 and 2014. Here’s how the top six low-value services compare.
Dr. Fendrick said a weakness of the paper is the years of the data (2007-2014). Some of the criteria around low-value care have changed since then. The age that a prostate-specific antigen test becomes low-value is now 70 years, for instance, instead of 75. He added that some of the figures attributed to non-PCP providers appear out of date.
Dr. Fendrick said, “I understand that there are Medicare patients who end up at a gastroenterologist or surgeon’s office to get colorectal cancer screening, but it would be very hard for me to believe that half of stress tests and over half of colon cancer screening over [age] 85 [years] and half of PSA for people over 75 did not have some type of referring clinicians involved. I certainly don’t think that would be the case in 2020-2021.”
Dr. Baum said those years were the latest years available for the data points needed for this analysis, but he and his colleagues were working to update the data for future publication.
Dr. Fendrick said not much has changed in recent years in terms of waste on low-value care, even with campaigns such as Choosing Wisely dedicated to identifying low-value services or procedures in each specialty.
“I believe there’s not a particular group of clinicians one way or the other who are actually doing any better now than they were 7 years ago,” he said. He would rather focus less on which specialties are associated with the most low-value care and more on the underlying policies that encourage low-value care.
“If you’re going to get paid for doing a stress test and get paid nothing or significantly less if you don’t, the incentives are in the wrong direction,” he said.
Dr. Fendrick said the pandemic era provides an opportunity to eliminate low-value care because use of those services has dropped drastically as resources have been diverted to COVID-19 patients and many services have been delayed or canceled.
He said he has been pushing an approach that providers should be paid more after the pandemic “to do the things we want them to do.”
As an example, he said, instead of paying $886 million on colonoscopies for people over the age of 85, “why don’t we put a policy in place that would make it better for patients by lowering cost sharing and better for providers by paying them more to do the service on the people who need it as opposed to the people who don’t?”
The research was funded by the American Board of Family Medicine Foundation. Dr. Baum and a coauthor reported receiving personal fees from American Board of Family Medicine Foundation during the conduct of the study. Another coauthor reported receiving personal fees from Collective Health, HealthRight 360, PLOS Medicine, and the New England Journal of Medicine, outside the submitted work. Dr. Fendrick disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Meta-analysis: No evidence that SNRIs relieve back pain
While some guidelines support serotonin norepinephrine reuptake inhibitors (SNRIs) as treatments for back pain, a new systematic review and meta-analysis of existing research found no firm evidence of a benefit. Adverse effects, however, are common.
“Our review shows that, although these medicines are effective, the effect is small and unlikely to be considered clinically important by most patients,” wrote the authors of the review, which appeared Jan. 20 in the BMJ. “Our review also showed that about two-thirds of patients using SNRIs experience adverse events.”
However, the report hinted that certain classes of antidepressants may provide significant relief in knee OA and sciatica.
According to a 2018 review, 10 of 15 clinical guidelines from around the world – including those of the American College of Physicians – recommended antidepressants as treatments for low back pain, and 2 advised against them. “Evidence supporting the use of antidepressants is, however, uncertain,” wrote the authors of the new review, led by Giovanni E. Ferreira, PhD, of the University of Sydney. “Systematic reviews of antidepressants for back pain and osteoarthritis have either not included several published trials, considered only one type of antidepressant (e.g., duloxetine), or failed to assess the certainty of evidence.”
For the new review, the authors analyzed 33 randomized, controlled trials with a total of 5,318 subjects. Both published data and unpublished data from clinical trial registries were included.
Back pain trials
A total of 19 trials examined back pain, mostly lower back pain (16 trials), and none lasted more than 1 year. Fifteen examined SNRIs while others looked at other kinds of antidepressants.
The researchers found that “the effect of SNRIs was small [on back pain] and below this review’s predetermined threshold of clinical importance. ... Evidence ranging from low to very low certainty showed no benefit of a range of antidepressant classes, including SSRIs [selective serotonin reuptake inhibitors], tetracyclic antidepressants, SARIs [serotonin antagonist and reuptake inhibitors], and NDRIs [norepinephrine and dopamine reuptake inhibitors] for pain and disability across follow-ups of 2 weeks or less, 3-13 weeks, and 3-12 months.”
Sciatica trials
Six trials examined antidepressants as treatments for sciatica. Very-low-certainty evidence suggested that SNRIs reduced pain at up to 2 weeks (1 trial, n = 50) but not at 3-13 weeks (3 trials, n = 96). The results of trials of tricyclic antidepressants (TCAs) were the opposite: low- to very-low-certainty evidence suggested the drugs didn’t reduce pain at up to 2 weeks (2 trials, n = 94) but did at 3-13 weeks (2 trials, n = 114) and 3-12 months (1 trial, n = 60).
“All sciatica trials were small, had imprecise estimates, and were at high risk of bias, which reduced the certainty of evidence to low and very low,” the authors cautioned. “This level of uncertainty indicates that the true estimate of effect of TCAs and SNRIs for sciatica is likely to be substantially different from what we estimated in our review.”
Knee OA trials
Eight trials examined SNRIs in knee OA. Moderate-certainty evidence linked the drugs to less pain at up to 2 weeks (four trials, n = 1,328) and low-certainty evidence linked them to less pain at 3-13 weeks (eight trials, n = 1,941). Low-certainty evidence also linked the drugs to less disability at 2 weeks or less (one trial, n = 353) and 3-13 weeks (seven trials, n = 1,810).
In knee OA, “the effect of SNRIs was small and below this review’s predetermined threshold of clinical importance,” the researchers wrote. “However, the lower limit of the confidence interval did contain clinically important effects for pain, but not for disability.”
Antidepressant side effects in trials
A total of 21 trials (n = 4,107) looked at side effects when antidepressants were studied as treatments for back pain and OA. Low-certainty evidence in 13 SNRI trials (n = 3,447) suggested a higher risk of any adverse events in antidepressant versus placebo (62.5% vs. 49.7%; relative risk, 1.23, 95% confidence interval, 1.16-1.30), but there was no significantly higher risk of serious adverse events in 10 SNRI trials with 3,309 subjects (1.6% vs. 1.3%; RR, 1.12, 95% CI, 0.61-2.07).
As for adverse effects of non-SNRIs, “the number of studies evaluating the safety of other antidepressant classes was small, trials were underpowered to detect harm, and the certainty of evidence ranged from low to very low,” the researchers wrote.
Going forward, the authors said that “large, definitive randomized trials that are free of industry ties are urgently needed to resolve uncertainties about the efficacy of antidepressants for sciatica and osteoarthritis highlighted by this review.”
‘Largely ineffective’ drug treatments
In an accompanying commentary, Martin Underwood, of the University of Warwick in Coventry, England, and Colin Tysall, of the University Hospitals of Coventry and Warwickshire, also in Coventry, noted that “drug treatments are largely ineffective for back pain and osteoarthritis and have the potential for serious harm. We need to work harder to help people with these disorders to live better with their pain without recourse to the prescription pad.”
However, they noted that SNRIs may still be helpful for patients with back pain or OA. “Absolute effect sizes for physical treatments for low-back pain are of similar magnitudes to those reported here and translate into numbers needed to treat of between five and nine. If the same were true for SNRIs, some people might choose to a try that option for a 1 in 10 chance of a worthwhile reduction in pain after 3 months. They can easily stop if treatment is ineffective or does not suit them.”
The research received no specific funding. The review authors disclosed relationships with GlaxoSmithKline (postgraduate scholarship), Pfizer (investigational product for two trials), and Flexeze (provision of heat wraps for a trial). Mr. Underwood reported being a director and shareholder of Clinvivo. Mr. Tysall reported no disclosures.
While some guidelines support serotonin norepinephrine reuptake inhibitors (SNRIs) as treatments for back pain, a new systematic review and meta-analysis of existing research found no firm evidence of a benefit. Adverse effects, however, are common.
“Our review shows that, although these medicines are effective, the effect is small and unlikely to be considered clinically important by most patients,” wrote the authors of the review, which appeared Jan. 20 in the BMJ. “Our review also showed that about two-thirds of patients using SNRIs experience adverse events.”
However, the report hinted that certain classes of antidepressants may provide significant relief in knee OA and sciatica.
According to a 2018 review, 10 of 15 clinical guidelines from around the world – including those of the American College of Physicians – recommended antidepressants as treatments for low back pain, and 2 advised against them. “Evidence supporting the use of antidepressants is, however, uncertain,” wrote the authors of the new review, led by Giovanni E. Ferreira, PhD, of the University of Sydney. “Systematic reviews of antidepressants for back pain and osteoarthritis have either not included several published trials, considered only one type of antidepressant (e.g., duloxetine), or failed to assess the certainty of evidence.”
For the new review, the authors analyzed 33 randomized, controlled trials with a total of 5,318 subjects. Both published data and unpublished data from clinical trial registries were included.
Back pain trials
A total of 19 trials examined back pain, mostly lower back pain (16 trials), and none lasted more than 1 year. Fifteen examined SNRIs while others looked at other kinds of antidepressants.
The researchers found that “the effect of SNRIs was small [on back pain] and below this review’s predetermined threshold of clinical importance. ... Evidence ranging from low to very low certainty showed no benefit of a range of antidepressant classes, including SSRIs [selective serotonin reuptake inhibitors], tetracyclic antidepressants, SARIs [serotonin antagonist and reuptake inhibitors], and NDRIs [norepinephrine and dopamine reuptake inhibitors] for pain and disability across follow-ups of 2 weeks or less, 3-13 weeks, and 3-12 months.”
Sciatica trials
Six trials examined antidepressants as treatments for sciatica. Very-low-certainty evidence suggested that SNRIs reduced pain at up to 2 weeks (1 trial, n = 50) but not at 3-13 weeks (3 trials, n = 96). The results of trials of tricyclic antidepressants (TCAs) were the opposite: low- to very-low-certainty evidence suggested the drugs didn’t reduce pain at up to 2 weeks (2 trials, n = 94) but did at 3-13 weeks (2 trials, n = 114) and 3-12 months (1 trial, n = 60).
“All sciatica trials were small, had imprecise estimates, and were at high risk of bias, which reduced the certainty of evidence to low and very low,” the authors cautioned. “This level of uncertainty indicates that the true estimate of effect of TCAs and SNRIs for sciatica is likely to be substantially different from what we estimated in our review.”
Knee OA trials
Eight trials examined SNRIs in knee OA. Moderate-certainty evidence linked the drugs to less pain at up to 2 weeks (four trials, n = 1,328) and low-certainty evidence linked them to less pain at 3-13 weeks (eight trials, n = 1,941). Low-certainty evidence also linked the drugs to less disability at 2 weeks or less (one trial, n = 353) and 3-13 weeks (seven trials, n = 1,810).
In knee OA, “the effect of SNRIs was small and below this review’s predetermined threshold of clinical importance,” the researchers wrote. “However, the lower limit of the confidence interval did contain clinically important effects for pain, but not for disability.”
Antidepressant side effects in trials
A total of 21 trials (n = 4,107) looked at side effects when antidepressants were studied as treatments for back pain and OA. Low-certainty evidence in 13 SNRI trials (n = 3,447) suggested a higher risk of any adverse events in antidepressant versus placebo (62.5% vs. 49.7%; relative risk, 1.23, 95% confidence interval, 1.16-1.30), but there was no significantly higher risk of serious adverse events in 10 SNRI trials with 3,309 subjects (1.6% vs. 1.3%; RR, 1.12, 95% CI, 0.61-2.07).
As for adverse effects of non-SNRIs, “the number of studies evaluating the safety of other antidepressant classes was small, trials were underpowered to detect harm, and the certainty of evidence ranged from low to very low,” the researchers wrote.
Going forward, the authors said that “large, definitive randomized trials that are free of industry ties are urgently needed to resolve uncertainties about the efficacy of antidepressants for sciatica and osteoarthritis highlighted by this review.”
‘Largely ineffective’ drug treatments
In an accompanying commentary, Martin Underwood, of the University of Warwick in Coventry, England, and Colin Tysall, of the University Hospitals of Coventry and Warwickshire, also in Coventry, noted that “drug treatments are largely ineffective for back pain and osteoarthritis and have the potential for serious harm. We need to work harder to help people with these disorders to live better with their pain without recourse to the prescription pad.”
However, they noted that SNRIs may still be helpful for patients with back pain or OA. “Absolute effect sizes for physical treatments for low-back pain are of similar magnitudes to those reported here and translate into numbers needed to treat of between five and nine. If the same were true for SNRIs, some people might choose to a try that option for a 1 in 10 chance of a worthwhile reduction in pain after 3 months. They can easily stop if treatment is ineffective or does not suit them.”
The research received no specific funding. The review authors disclosed relationships with GlaxoSmithKline (postgraduate scholarship), Pfizer (investigational product for two trials), and Flexeze (provision of heat wraps for a trial). Mr. Underwood reported being a director and shareholder of Clinvivo. Mr. Tysall reported no disclosures.
While some guidelines support serotonin norepinephrine reuptake inhibitors (SNRIs) as treatments for back pain, a new systematic review and meta-analysis of existing research found no firm evidence of a benefit. Adverse effects, however, are common.
“Our review shows that, although these medicines are effective, the effect is small and unlikely to be considered clinically important by most patients,” wrote the authors of the review, which appeared Jan. 20 in the BMJ. “Our review also showed that about two-thirds of patients using SNRIs experience adverse events.”
However, the report hinted that certain classes of antidepressants may provide significant relief in knee OA and sciatica.
According to a 2018 review, 10 of 15 clinical guidelines from around the world – including those of the American College of Physicians – recommended antidepressants as treatments for low back pain, and 2 advised against them. “Evidence supporting the use of antidepressants is, however, uncertain,” wrote the authors of the new review, led by Giovanni E. Ferreira, PhD, of the University of Sydney. “Systematic reviews of antidepressants for back pain and osteoarthritis have either not included several published trials, considered only one type of antidepressant (e.g., duloxetine), or failed to assess the certainty of evidence.”
For the new review, the authors analyzed 33 randomized, controlled trials with a total of 5,318 subjects. Both published data and unpublished data from clinical trial registries were included.
Back pain trials
A total of 19 trials examined back pain, mostly lower back pain (16 trials), and none lasted more than 1 year. Fifteen examined SNRIs while others looked at other kinds of antidepressants.
The researchers found that “the effect of SNRIs was small [on back pain] and below this review’s predetermined threshold of clinical importance. ... Evidence ranging from low to very low certainty showed no benefit of a range of antidepressant classes, including SSRIs [selective serotonin reuptake inhibitors], tetracyclic antidepressants, SARIs [serotonin antagonist and reuptake inhibitors], and NDRIs [norepinephrine and dopamine reuptake inhibitors] for pain and disability across follow-ups of 2 weeks or less, 3-13 weeks, and 3-12 months.”
Sciatica trials
Six trials examined antidepressants as treatments for sciatica. Very-low-certainty evidence suggested that SNRIs reduced pain at up to 2 weeks (1 trial, n = 50) but not at 3-13 weeks (3 trials, n = 96). The results of trials of tricyclic antidepressants (TCAs) were the opposite: low- to very-low-certainty evidence suggested the drugs didn’t reduce pain at up to 2 weeks (2 trials, n = 94) but did at 3-13 weeks (2 trials, n = 114) and 3-12 months (1 trial, n = 60).
“All sciatica trials were small, had imprecise estimates, and were at high risk of bias, which reduced the certainty of evidence to low and very low,” the authors cautioned. “This level of uncertainty indicates that the true estimate of effect of TCAs and SNRIs for sciatica is likely to be substantially different from what we estimated in our review.”
Knee OA trials
Eight trials examined SNRIs in knee OA. Moderate-certainty evidence linked the drugs to less pain at up to 2 weeks (four trials, n = 1,328) and low-certainty evidence linked them to less pain at 3-13 weeks (eight trials, n = 1,941). Low-certainty evidence also linked the drugs to less disability at 2 weeks or less (one trial, n = 353) and 3-13 weeks (seven trials, n = 1,810).
In knee OA, “the effect of SNRIs was small and below this review’s predetermined threshold of clinical importance,” the researchers wrote. “However, the lower limit of the confidence interval did contain clinically important effects for pain, but not for disability.”
Antidepressant side effects in trials
A total of 21 trials (n = 4,107) looked at side effects when antidepressants were studied as treatments for back pain and OA. Low-certainty evidence in 13 SNRI trials (n = 3,447) suggested a higher risk of any adverse events in antidepressant versus placebo (62.5% vs. 49.7%; relative risk, 1.23, 95% confidence interval, 1.16-1.30), but there was no significantly higher risk of serious adverse events in 10 SNRI trials with 3,309 subjects (1.6% vs. 1.3%; RR, 1.12, 95% CI, 0.61-2.07).
As for adverse effects of non-SNRIs, “the number of studies evaluating the safety of other antidepressant classes was small, trials were underpowered to detect harm, and the certainty of evidence ranged from low to very low,” the researchers wrote.
Going forward, the authors said that “large, definitive randomized trials that are free of industry ties are urgently needed to resolve uncertainties about the efficacy of antidepressants for sciatica and osteoarthritis highlighted by this review.”
‘Largely ineffective’ drug treatments
In an accompanying commentary, Martin Underwood, of the University of Warwick in Coventry, England, and Colin Tysall, of the University Hospitals of Coventry and Warwickshire, also in Coventry, noted that “drug treatments are largely ineffective for back pain and osteoarthritis and have the potential for serious harm. We need to work harder to help people with these disorders to live better with their pain without recourse to the prescription pad.”
However, they noted that SNRIs may still be helpful for patients with back pain or OA. “Absolute effect sizes for physical treatments for low-back pain are of similar magnitudes to those reported here and translate into numbers needed to treat of between five and nine. If the same were true for SNRIs, some people might choose to a try that option for a 1 in 10 chance of a worthwhile reduction in pain after 3 months. They can easily stop if treatment is ineffective or does not suit them.”
The research received no specific funding. The review authors disclosed relationships with GlaxoSmithKline (postgraduate scholarship), Pfizer (investigational product for two trials), and Flexeze (provision of heat wraps for a trial). Mr. Underwood reported being a director and shareholder of Clinvivo. Mr. Tysall reported no disclosures.
FROM THE BMJ
Greater reductions in knee OA pain seen with supportive rather than flexible shoes
according to a randomized trial that included more than 160 patients.
“Contrary to our hypothesis, flat flexible shoes were not superior to stable supportive shoes,” reported Kade L. Paterson, PhD, of the University of Melbourne, and colleagues. Their study was published Jan. 12 in Annals of Internal Medicine.
Research gap
Abnormal knee joint loading has been implicated in the pathogenesis of knee OA. Guidelines recommend that patients wear appropriate footwear, but research has not established which shoes are best.
The 2019 American College of Rheumatology clinical guidelines note that “optimal footwear is likely to be of considerable importance for those with knee and/or hip OA,” but “the available studies do not define the best type of footwear to improve specific outcomes for knee or hip OA.”
Some doctors call for thick, shock-absorbing soles and arch supports, based on expert opinion. On the other hand, studies have found that knee loading is lower with flat flexible shoes, and preliminary evidence has suggested that flat flexible shoes may improve OA symptoms, the investigators said.
To study this question, they enrolled in their trial 164 patients aged 50 years and older who had radiographic medial knee OA. Participants had knee pain on most days of the previous month, tibiofemoral osteophytes, and moderate to severe tibiofemoral OA.
The researchers randomly assigned 82 participants to flat flexible shoes and 82 participants to stable supportive shoes, worn for at least 6 hours a day for 6 months.
In the trial, flat flexible shoes included Merrell Bare Access (men’s and women’s), Vivobarefoot Primus Lite (men’s and women’s), Vivobarefoot Mata Canvas (men’s), Converse Dainty Low (women’s), and Lacoste Marice (men’s).
Stable supportive shoes included ASICS Kayano (men’s and women’s), Merrell Jungle Moc (men’s), Nike Air Max 90 Ultra (women’s), Rockport Edge Hill (men’s), and New Balance 624 (women’s).
After participants were randomly assigned to a group, they chose two different pairs of shoes from their assigned footwear group.
“Participants were not told that the purpose of the study was to compare flat flexible with stable supportive shoes,” the researchers noted. “Instead, they were informed only that the trial was comparing the effects of ‘different shoes’ on knee OA symptoms.”
The primary outcomes were changes in walking pain on a 0-10 scale and physical function as assessed by the Western Ontario and McMaster Universities Osteoarthritis Index subscale at 6 months. The researchers also assessed other measures of pain and function, physical activity, and quality of life.
In all, 161 participants reported 6-month primary outcomes. The between-group difference in change in pain favored stable supportive shoes (mean difference, 1.1 units). In the flat flexible shoe group, overall average knee pain while walking decreased from 6.3 at baseline to 5.2 at 6 months. In the stable supportive shoe group, knee pain while walking decreased from 6.1 to 4.
In addition, improvements in knee-related quality of life and ipsilateral hip pain favored stable supportive shoes.
Participants who wore stable supportive shoes also were less likely to report adverse events, compared with those who wore flat flexible shoes (15% vs. 32%). Knee pain, ankle or foot pain, and shin or calf pain were among the adverse events reported.
‘Important work’
“This study suggests that more supportive shoes may help some patients with knee osteoarthritis feel better,” Constance R. Chu, MD, professor of orthopedic surgery at Stanford (Calif.) University, said in an interview. “Shoes, insoles, wedges, and high heels have been shown to change loading of the knee related to knee pain and osteoarthritis ... This is important work toward providing more specific information on the optimum shoes for people with different patterns and types of arthritis to reduce pain and disability from early knee OA.”
The reported changes in pain may be clinically meaningful for many but not all patients, the authors wrote. “Despite biomechanical evidence showing that flat flexible shoes reduce medial knee load compared with stable supportive shoes, our findings show that this does not translate to improved knee osteoarthritis symptoms,” they said. “This may be because relationships between knee loading and symptoms are not as strong as previously thought, or because the small reductions in medial knee load with flat flexible shoes are insufficient to substantively improve pain and function.”
The trial did not include a control group of patients who wore their usual shoes, and it focused on a select subgroup of patients with knee OA, which may limit the study’s generalizability, the authors noted. The study excluded people with lateral joint space narrowing greater than or equal to medial, those with recent or planned knee surgery, and those who were using shoe orthoses or customized shoes.
The study was supported by grants from the National Health and Medical Research Council. Dr. Chu had no relevant disclosures.
according to a randomized trial that included more than 160 patients.
“Contrary to our hypothesis, flat flexible shoes were not superior to stable supportive shoes,” reported Kade L. Paterson, PhD, of the University of Melbourne, and colleagues. Their study was published Jan. 12 in Annals of Internal Medicine.
Research gap
Abnormal knee joint loading has been implicated in the pathogenesis of knee OA. Guidelines recommend that patients wear appropriate footwear, but research has not established which shoes are best.
The 2019 American College of Rheumatology clinical guidelines note that “optimal footwear is likely to be of considerable importance for those with knee and/or hip OA,” but “the available studies do not define the best type of footwear to improve specific outcomes for knee or hip OA.”
Some doctors call for thick, shock-absorbing soles and arch supports, based on expert opinion. On the other hand, studies have found that knee loading is lower with flat flexible shoes, and preliminary evidence has suggested that flat flexible shoes may improve OA symptoms, the investigators said.
To study this question, they enrolled in their trial 164 patients aged 50 years and older who had radiographic medial knee OA. Participants had knee pain on most days of the previous month, tibiofemoral osteophytes, and moderate to severe tibiofemoral OA.
The researchers randomly assigned 82 participants to flat flexible shoes and 82 participants to stable supportive shoes, worn for at least 6 hours a day for 6 months.
In the trial, flat flexible shoes included Merrell Bare Access (men’s and women’s), Vivobarefoot Primus Lite (men’s and women’s), Vivobarefoot Mata Canvas (men’s), Converse Dainty Low (women’s), and Lacoste Marice (men’s).
Stable supportive shoes included ASICS Kayano (men’s and women’s), Merrell Jungle Moc (men’s), Nike Air Max 90 Ultra (women’s), Rockport Edge Hill (men’s), and New Balance 624 (women’s).
After participants were randomly assigned to a group, they chose two different pairs of shoes from their assigned footwear group.
“Participants were not told that the purpose of the study was to compare flat flexible with stable supportive shoes,” the researchers noted. “Instead, they were informed only that the trial was comparing the effects of ‘different shoes’ on knee OA symptoms.”
The primary outcomes were changes in walking pain on a 0-10 scale and physical function as assessed by the Western Ontario and McMaster Universities Osteoarthritis Index subscale at 6 months. The researchers also assessed other measures of pain and function, physical activity, and quality of life.
In all, 161 participants reported 6-month primary outcomes. The between-group difference in change in pain favored stable supportive shoes (mean difference, 1.1 units). In the flat flexible shoe group, overall average knee pain while walking decreased from 6.3 at baseline to 5.2 at 6 months. In the stable supportive shoe group, knee pain while walking decreased from 6.1 to 4.
In addition, improvements in knee-related quality of life and ipsilateral hip pain favored stable supportive shoes.
Participants who wore stable supportive shoes also were less likely to report adverse events, compared with those who wore flat flexible shoes (15% vs. 32%). Knee pain, ankle or foot pain, and shin or calf pain were among the adverse events reported.
‘Important work’
“This study suggests that more supportive shoes may help some patients with knee osteoarthritis feel better,” Constance R. Chu, MD, professor of orthopedic surgery at Stanford (Calif.) University, said in an interview. “Shoes, insoles, wedges, and high heels have been shown to change loading of the knee related to knee pain and osteoarthritis ... This is important work toward providing more specific information on the optimum shoes for people with different patterns and types of arthritis to reduce pain and disability from early knee OA.”
The reported changes in pain may be clinically meaningful for many but not all patients, the authors wrote. “Despite biomechanical evidence showing that flat flexible shoes reduce medial knee load compared with stable supportive shoes, our findings show that this does not translate to improved knee osteoarthritis symptoms,” they said. “This may be because relationships between knee loading and symptoms are not as strong as previously thought, or because the small reductions in medial knee load with flat flexible shoes are insufficient to substantively improve pain and function.”
The trial did not include a control group of patients who wore their usual shoes, and it focused on a select subgroup of patients with knee OA, which may limit the study’s generalizability, the authors noted. The study excluded people with lateral joint space narrowing greater than or equal to medial, those with recent or planned knee surgery, and those who were using shoe orthoses or customized shoes.
The study was supported by grants from the National Health and Medical Research Council. Dr. Chu had no relevant disclosures.
according to a randomized trial that included more than 160 patients.
“Contrary to our hypothesis, flat flexible shoes were not superior to stable supportive shoes,” reported Kade L. Paterson, PhD, of the University of Melbourne, and colleagues. Their study was published Jan. 12 in Annals of Internal Medicine.
Research gap
Abnormal knee joint loading has been implicated in the pathogenesis of knee OA. Guidelines recommend that patients wear appropriate footwear, but research has not established which shoes are best.
The 2019 American College of Rheumatology clinical guidelines note that “optimal footwear is likely to be of considerable importance for those with knee and/or hip OA,” but “the available studies do not define the best type of footwear to improve specific outcomes for knee or hip OA.”
Some doctors call for thick, shock-absorbing soles and arch supports, based on expert opinion. On the other hand, studies have found that knee loading is lower with flat flexible shoes, and preliminary evidence has suggested that flat flexible shoes may improve OA symptoms, the investigators said.
To study this question, they enrolled in their trial 164 patients aged 50 years and older who had radiographic medial knee OA. Participants had knee pain on most days of the previous month, tibiofemoral osteophytes, and moderate to severe tibiofemoral OA.
The researchers randomly assigned 82 participants to flat flexible shoes and 82 participants to stable supportive shoes, worn for at least 6 hours a day for 6 months.
In the trial, flat flexible shoes included Merrell Bare Access (men’s and women’s), Vivobarefoot Primus Lite (men’s and women’s), Vivobarefoot Mata Canvas (men’s), Converse Dainty Low (women’s), and Lacoste Marice (men’s).
Stable supportive shoes included ASICS Kayano (men’s and women’s), Merrell Jungle Moc (men’s), Nike Air Max 90 Ultra (women’s), Rockport Edge Hill (men’s), and New Balance 624 (women’s).
After participants were randomly assigned to a group, they chose two different pairs of shoes from their assigned footwear group.
“Participants were not told that the purpose of the study was to compare flat flexible with stable supportive shoes,” the researchers noted. “Instead, they were informed only that the trial was comparing the effects of ‘different shoes’ on knee OA symptoms.”
The primary outcomes were changes in walking pain on a 0-10 scale and physical function as assessed by the Western Ontario and McMaster Universities Osteoarthritis Index subscale at 6 months. The researchers also assessed other measures of pain and function, physical activity, and quality of life.
In all, 161 participants reported 6-month primary outcomes. The between-group difference in change in pain favored stable supportive shoes (mean difference, 1.1 units). In the flat flexible shoe group, overall average knee pain while walking decreased from 6.3 at baseline to 5.2 at 6 months. In the stable supportive shoe group, knee pain while walking decreased from 6.1 to 4.
In addition, improvements in knee-related quality of life and ipsilateral hip pain favored stable supportive shoes.
Participants who wore stable supportive shoes also were less likely to report adverse events, compared with those who wore flat flexible shoes (15% vs. 32%). Knee pain, ankle or foot pain, and shin or calf pain were among the adverse events reported.
‘Important work’
“This study suggests that more supportive shoes may help some patients with knee osteoarthritis feel better,” Constance R. Chu, MD, professor of orthopedic surgery at Stanford (Calif.) University, said in an interview. “Shoes, insoles, wedges, and high heels have been shown to change loading of the knee related to knee pain and osteoarthritis ... This is important work toward providing more specific information on the optimum shoes for people with different patterns and types of arthritis to reduce pain and disability from early knee OA.”
The reported changes in pain may be clinically meaningful for many but not all patients, the authors wrote. “Despite biomechanical evidence showing that flat flexible shoes reduce medial knee load compared with stable supportive shoes, our findings show that this does not translate to improved knee osteoarthritis symptoms,” they said. “This may be because relationships between knee loading and symptoms are not as strong as previously thought, or because the small reductions in medial knee load with flat flexible shoes are insufficient to substantively improve pain and function.”
The trial did not include a control group of patients who wore their usual shoes, and it focused on a select subgroup of patients with knee OA, which may limit the study’s generalizability, the authors noted. The study excluded people with lateral joint space narrowing greater than or equal to medial, those with recent or planned knee surgery, and those who were using shoe orthoses or customized shoes.
The study was supported by grants from the National Health and Medical Research Council. Dr. Chu had no relevant disclosures.
FROM ANNALS OF INTERNAL MEDICINE
EULAR recommendations define strategies to improve adherence in RMDs
Clinicians who care for patients with rheumatic and musculoskeletal diseases (RMDs) can now refer to a new set of strategies and points to consider from a European League Against Rheumatism (EULAR) task force in building a patient-centered approach to improve adherence to treatments.
Nonadherence to treatments is concerning given that 30%-80% of patients who have RMDs are thought to not follow a recommended treatment plan according to their physicians’ instructions, according to first author Valentin Ritschl of the Medical University of Vienna and colleagues.
“The problem of poor adherence is addressed in some EULAR recommendations/points to consider on the management of specific health conditions or on the role of professionals,” Mr. Ritschl said in an interview. “However, all these recommendations focus on limited aspects of nonadherence and do not cover the multifaceted nature of this phenomenon.”
Mr. Ritschl and colleagues conducted an extensive systematic literature review, the results of which they presented to a task force consisting of a panel of international experts hailing from 12 different countries. The task force included rheumatologists and other health professionals in rheumatology, as well as patient representatives.
The collaboration resulted in investigators crafting a definition of adherence in addition to drafting four overarching principles and nine points to consider, which were published Dec. 18 in Annals of the Rheumatic Diseases.
They defined adherence as “the extent to which a person’s behavior corresponds with the agreed prescription, of pharmacological or nonpharmacological treatments, by a health care provider.”
The four overarching principles emphasize the following concepts: that adherence affects outcomes in people who have RMDs; the importance of shared decision-making, with the understanding that the adherence describes the patient’s behavior “following an agreed prescription”; that numerous factors can affect adherence; and the notion of adherence being a dynamic process that, consequently, requires continuous evaluation.
Among the nine points to consider, Mr. Ritschl and coauthors encouraged all health care providers involved in caring for RMD patients to assume responsibility for promoting adherence. Practitioners should also strive to create an ongoing, open dialogue to discuss adherence, especially in cases in which the patient’s RMD is not well controlled. The patient-centered recommendations include taking into account the patient’s goals and preferences because these greatly contribute to the patient’s ability to adhere to any medication regimen. Another arm of that exploration also requires the medical professional to evaluate any circumstances that could bear a negative effect on the patient’s adherence – whether it be medication access issues related to cost or availability, or functional challenges such as memory, motivation, or complexity of the medication regimen.
Mr. Ritschl believed the task force’s recommendations will add value and help improve overall outcomes in RMD population management.
“Until today, there are no recommendations or points to consider developed in order to support our patients to be adherent to the agreed treatment plan,” he said. “In our project/initiative, we therefore developed for the first time points to consider to detect, assess, and manage nonadherence in people with RMDs.”
Additionally, the recommendations offer some strategic insights to help improve clinical trials because the deleterious effects of nonadherence also affect study results.
Looking ahead, Mr. Ritschl said randomized, controlled trials are necessary to test strategies that might improve adherence. He strongly emphasized the importance of designing future research studies that are heavily patient centered and effective for shared decision-making.
The project was funded by EULAR. Mr. Ritschl reported having no disclosures, but many of his coauthors reported financial relationships with pharmaceutical companies.
SOURCE: Ritschl V et al. Ann Rheum Dis. 2020 Dec 18. doi: 10.1136/annrheumdis-2020-218986.
Clinicians who care for patients with rheumatic and musculoskeletal diseases (RMDs) can now refer to a new set of strategies and points to consider from a European League Against Rheumatism (EULAR) task force in building a patient-centered approach to improve adherence to treatments.
Nonadherence to treatments is concerning given that 30%-80% of patients who have RMDs are thought to not follow a recommended treatment plan according to their physicians’ instructions, according to first author Valentin Ritschl of the Medical University of Vienna and colleagues.
“The problem of poor adherence is addressed in some EULAR recommendations/points to consider on the management of specific health conditions or on the role of professionals,” Mr. Ritschl said in an interview. “However, all these recommendations focus on limited aspects of nonadherence and do not cover the multifaceted nature of this phenomenon.”
Mr. Ritschl and colleagues conducted an extensive systematic literature review, the results of which they presented to a task force consisting of a panel of international experts hailing from 12 different countries. The task force included rheumatologists and other health professionals in rheumatology, as well as patient representatives.
The collaboration resulted in investigators crafting a definition of adherence in addition to drafting four overarching principles and nine points to consider, which were published Dec. 18 in Annals of the Rheumatic Diseases.
They defined adherence as “the extent to which a person’s behavior corresponds with the agreed prescription, of pharmacological or nonpharmacological treatments, by a health care provider.”
The four overarching principles emphasize the following concepts: that adherence affects outcomes in people who have RMDs; the importance of shared decision-making, with the understanding that the adherence describes the patient’s behavior “following an agreed prescription”; that numerous factors can affect adherence; and the notion of adherence being a dynamic process that, consequently, requires continuous evaluation.
Among the nine points to consider, Mr. Ritschl and coauthors encouraged all health care providers involved in caring for RMD patients to assume responsibility for promoting adherence. Practitioners should also strive to create an ongoing, open dialogue to discuss adherence, especially in cases in which the patient’s RMD is not well controlled. The patient-centered recommendations include taking into account the patient’s goals and preferences because these greatly contribute to the patient’s ability to adhere to any medication regimen. Another arm of that exploration also requires the medical professional to evaluate any circumstances that could bear a negative effect on the patient’s adherence – whether it be medication access issues related to cost or availability, or functional challenges such as memory, motivation, or complexity of the medication regimen.
Mr. Ritschl believed the task force’s recommendations will add value and help improve overall outcomes in RMD population management.
“Until today, there are no recommendations or points to consider developed in order to support our patients to be adherent to the agreed treatment plan,” he said. “In our project/initiative, we therefore developed for the first time points to consider to detect, assess, and manage nonadherence in people with RMDs.”
Additionally, the recommendations offer some strategic insights to help improve clinical trials because the deleterious effects of nonadherence also affect study results.
Looking ahead, Mr. Ritschl said randomized, controlled trials are necessary to test strategies that might improve adherence. He strongly emphasized the importance of designing future research studies that are heavily patient centered and effective for shared decision-making.
The project was funded by EULAR. Mr. Ritschl reported having no disclosures, but many of his coauthors reported financial relationships with pharmaceutical companies.
SOURCE: Ritschl V et al. Ann Rheum Dis. 2020 Dec 18. doi: 10.1136/annrheumdis-2020-218986.
Clinicians who care for patients with rheumatic and musculoskeletal diseases (RMDs) can now refer to a new set of strategies and points to consider from a European League Against Rheumatism (EULAR) task force in building a patient-centered approach to improve adherence to treatments.
Nonadherence to treatments is concerning given that 30%-80% of patients who have RMDs are thought to not follow a recommended treatment plan according to their physicians’ instructions, according to first author Valentin Ritschl of the Medical University of Vienna and colleagues.
“The problem of poor adherence is addressed in some EULAR recommendations/points to consider on the management of specific health conditions or on the role of professionals,” Mr. Ritschl said in an interview. “However, all these recommendations focus on limited aspects of nonadherence and do not cover the multifaceted nature of this phenomenon.”
Mr. Ritschl and colleagues conducted an extensive systematic literature review, the results of which they presented to a task force consisting of a panel of international experts hailing from 12 different countries. The task force included rheumatologists and other health professionals in rheumatology, as well as patient representatives.
The collaboration resulted in investigators crafting a definition of adherence in addition to drafting four overarching principles and nine points to consider, which were published Dec. 18 in Annals of the Rheumatic Diseases.
They defined adherence as “the extent to which a person’s behavior corresponds with the agreed prescription, of pharmacological or nonpharmacological treatments, by a health care provider.”
The four overarching principles emphasize the following concepts: that adherence affects outcomes in people who have RMDs; the importance of shared decision-making, with the understanding that the adherence describes the patient’s behavior “following an agreed prescription”; that numerous factors can affect adherence; and the notion of adherence being a dynamic process that, consequently, requires continuous evaluation.
Among the nine points to consider, Mr. Ritschl and coauthors encouraged all health care providers involved in caring for RMD patients to assume responsibility for promoting adherence. Practitioners should also strive to create an ongoing, open dialogue to discuss adherence, especially in cases in which the patient’s RMD is not well controlled. The patient-centered recommendations include taking into account the patient’s goals and preferences because these greatly contribute to the patient’s ability to adhere to any medication regimen. Another arm of that exploration also requires the medical professional to evaluate any circumstances that could bear a negative effect on the patient’s adherence – whether it be medication access issues related to cost or availability, or functional challenges such as memory, motivation, or complexity of the medication regimen.
Mr. Ritschl believed the task force’s recommendations will add value and help improve overall outcomes in RMD population management.
“Until today, there are no recommendations or points to consider developed in order to support our patients to be adherent to the agreed treatment plan,” he said. “In our project/initiative, we therefore developed for the first time points to consider to detect, assess, and manage nonadherence in people with RMDs.”
Additionally, the recommendations offer some strategic insights to help improve clinical trials because the deleterious effects of nonadherence also affect study results.
Looking ahead, Mr. Ritschl said randomized, controlled trials are necessary to test strategies that might improve adherence. He strongly emphasized the importance of designing future research studies that are heavily patient centered and effective for shared decision-making.
The project was funded by EULAR. Mr. Ritschl reported having no disclosures, but many of his coauthors reported financial relationships with pharmaceutical companies.
SOURCE: Ritschl V et al. Ann Rheum Dis. 2020 Dec 18. doi: 10.1136/annrheumdis-2020-218986.
FROM ANNALS OF THE RHEUMATIC DISEASES
Radiofrequency ablation blocks hip, shoulder arthritis pain
Osteoarthritis patients report significant pain relief after treatment with cooled radiofrequency ablation, a new technique that “stuns” sensory nerves in shoulder and hip joints to reduce – and sometimes eliminate – pain.
“We send a small current to the sensory nerve to heat up the tissue and disrupt the fibers,” study lead author Felix Gonzalez, MD, of Emory University, Atlanta, said in an interview. “The effect is that the transmission of pain is significantly slowed or halted altogether.
“We damage something to fix something,” Dr. Gonzalez continued. “We target only the problematic nerve and get a very localized effect.”
Two-phase treatment
The treatment is performed in two phases. First, patients with shoulder pain are given an anesthetic to block their suprascapular, lateral pectoral, and axillary sensory articular nerves. Patients with hip pain have their obturator and femoral sensory articular nerves blocked.
A week or two later, the same nerves are treated with cooled radiofrequency ablation. Guided by x-ray imaging, a clinician heats up the affected nerve tissue using the tip of a needle, which is pointed at the nerve. “It’s a 22-gauge needle, slightly thicker than an acupuncture needle,” Dr. Gonzalez explained. “We heat up the nerve for about 2 minutes to about 60 degrees Celsius – it stuns the nerve,” he said.
“The result disrupts or slows down pain transmission while leaving the nerve intact.”
To test the efficacy of the technique, researchers treated 12 shoulders in patients with an average age of 61 years, and 11 hips in patients with an average age of 62 years.
Three months after treatment, patients with hip pain reported improvement in Hip Disability and Osteoarthritis Outcome Score (HOOS) from a baseline of 17.0 to 52.9 (P < .0001).
Shoulder pain was also reduced significantly. Using the American Shoulder and Elbow Surgeons (ASES) score, researchers reported an improvement from 17.2 (±6.6) at baseline to 65.7 (±5.9) at 3 months (P < .0001).
“We are targeting a subset of patients for this that don’t qualify for surgery,” Dr. Gonzalez noted. For patients with a body mass index above 35, or a history of hypertension, heart disease, or multiple strokes, opioids are the most common treatment, he said.
These patients “fall through the cracks,” he explained. Those who have mild to moderate pain are managed with physical therapy and injections, and those with severe pain go into surgery. “But what about the ones in the middle ... who are not eligible for surgery? They are at risk for opioid overuse,” he said. “So this treatment is a good option for them.”
Treats the symptoms, not the cause
“This study shows the efficacy of this method in taking care of shoulder and hip pain,” Luca Maria Sconfienza, MD, PhD, of Galeazzi Orthopedic Hospital in Milan, said in an interview. Dr. Sconfienza was not involved in Dr. Gonzalez’s study.
However, like corticosteroid injections, “the drawback of radiofrequency ablation is the fact that it only treats the symptoms and not the cause, and efficacy is usually limited over time,” she said.
Dr. Sconfienza said this study leaves her with three pertinent questions. “First, whether pain control extends beyond the 3-month follow-up reported by authors in the abstract; second, [what] is the efficacy of this method compared to other interventions (e.g., physical therapy, injections) or to doing nothing; and last, radiofrequency ablation is usually not a cheap treatment, thus a cost-efficacy analysis would be desirable, especially in comparison to other procedures.”
Dr. Gonzalez and Dr. Sconfienza have nothing relevant to disclose.
A version of this article originally appeared on Medscape.com.
Osteoarthritis patients report significant pain relief after treatment with cooled radiofrequency ablation, a new technique that “stuns” sensory nerves in shoulder and hip joints to reduce – and sometimes eliminate – pain.
“We send a small current to the sensory nerve to heat up the tissue and disrupt the fibers,” study lead author Felix Gonzalez, MD, of Emory University, Atlanta, said in an interview. “The effect is that the transmission of pain is significantly slowed or halted altogether.
“We damage something to fix something,” Dr. Gonzalez continued. “We target only the problematic nerve and get a very localized effect.”
Two-phase treatment
The treatment is performed in two phases. First, patients with shoulder pain are given an anesthetic to block their suprascapular, lateral pectoral, and axillary sensory articular nerves. Patients with hip pain have their obturator and femoral sensory articular nerves blocked.
A week or two later, the same nerves are treated with cooled radiofrequency ablation. Guided by x-ray imaging, a clinician heats up the affected nerve tissue using the tip of a needle, which is pointed at the nerve. “It’s a 22-gauge needle, slightly thicker than an acupuncture needle,” Dr. Gonzalez explained. “We heat up the nerve for about 2 minutes to about 60 degrees Celsius – it stuns the nerve,” he said.
“The result disrupts or slows down pain transmission while leaving the nerve intact.”
To test the efficacy of the technique, researchers treated 12 shoulders in patients with an average age of 61 years, and 11 hips in patients with an average age of 62 years.
Three months after treatment, patients with hip pain reported improvement in Hip Disability and Osteoarthritis Outcome Score (HOOS) from a baseline of 17.0 to 52.9 (P < .0001).
Shoulder pain was also reduced significantly. Using the American Shoulder and Elbow Surgeons (ASES) score, researchers reported an improvement from 17.2 (±6.6) at baseline to 65.7 (±5.9) at 3 months (P < .0001).
“We are targeting a subset of patients for this that don’t qualify for surgery,” Dr. Gonzalez noted. For patients with a body mass index above 35, or a history of hypertension, heart disease, or multiple strokes, opioids are the most common treatment, he said.
These patients “fall through the cracks,” he explained. Those who have mild to moderate pain are managed with physical therapy and injections, and those with severe pain go into surgery. “But what about the ones in the middle ... who are not eligible for surgery? They are at risk for opioid overuse,” he said. “So this treatment is a good option for them.”
Treats the symptoms, not the cause
“This study shows the efficacy of this method in taking care of shoulder and hip pain,” Luca Maria Sconfienza, MD, PhD, of Galeazzi Orthopedic Hospital in Milan, said in an interview. Dr. Sconfienza was not involved in Dr. Gonzalez’s study.
However, like corticosteroid injections, “the drawback of radiofrequency ablation is the fact that it only treats the symptoms and not the cause, and efficacy is usually limited over time,” she said.
Dr. Sconfienza said this study leaves her with three pertinent questions. “First, whether pain control extends beyond the 3-month follow-up reported by authors in the abstract; second, [what] is the efficacy of this method compared to other interventions (e.g., physical therapy, injections) or to doing nothing; and last, radiofrequency ablation is usually not a cheap treatment, thus a cost-efficacy analysis would be desirable, especially in comparison to other procedures.”
Dr. Gonzalez and Dr. Sconfienza have nothing relevant to disclose.
A version of this article originally appeared on Medscape.com.
Osteoarthritis patients report significant pain relief after treatment with cooled radiofrequency ablation, a new technique that “stuns” sensory nerves in shoulder and hip joints to reduce – and sometimes eliminate – pain.
“We send a small current to the sensory nerve to heat up the tissue and disrupt the fibers,” study lead author Felix Gonzalez, MD, of Emory University, Atlanta, said in an interview. “The effect is that the transmission of pain is significantly slowed or halted altogether.
“We damage something to fix something,” Dr. Gonzalez continued. “We target only the problematic nerve and get a very localized effect.”
Two-phase treatment
The treatment is performed in two phases. First, patients with shoulder pain are given an anesthetic to block their suprascapular, lateral pectoral, and axillary sensory articular nerves. Patients with hip pain have their obturator and femoral sensory articular nerves blocked.
A week or two later, the same nerves are treated with cooled radiofrequency ablation. Guided by x-ray imaging, a clinician heats up the affected nerve tissue using the tip of a needle, which is pointed at the nerve. “It’s a 22-gauge needle, slightly thicker than an acupuncture needle,” Dr. Gonzalez explained. “We heat up the nerve for about 2 minutes to about 60 degrees Celsius – it stuns the nerve,” he said.
“The result disrupts or slows down pain transmission while leaving the nerve intact.”
To test the efficacy of the technique, researchers treated 12 shoulders in patients with an average age of 61 years, and 11 hips in patients with an average age of 62 years.
Three months after treatment, patients with hip pain reported improvement in Hip Disability and Osteoarthritis Outcome Score (HOOS) from a baseline of 17.0 to 52.9 (P < .0001).
Shoulder pain was also reduced significantly. Using the American Shoulder and Elbow Surgeons (ASES) score, researchers reported an improvement from 17.2 (±6.6) at baseline to 65.7 (±5.9) at 3 months (P < .0001).
“We are targeting a subset of patients for this that don’t qualify for surgery,” Dr. Gonzalez noted. For patients with a body mass index above 35, or a history of hypertension, heart disease, or multiple strokes, opioids are the most common treatment, he said.
These patients “fall through the cracks,” he explained. Those who have mild to moderate pain are managed with physical therapy and injections, and those with severe pain go into surgery. “But what about the ones in the middle ... who are not eligible for surgery? They are at risk for opioid overuse,” he said. “So this treatment is a good option for them.”
Treats the symptoms, not the cause
“This study shows the efficacy of this method in taking care of shoulder and hip pain,” Luca Maria Sconfienza, MD, PhD, of Galeazzi Orthopedic Hospital in Milan, said in an interview. Dr. Sconfienza was not involved in Dr. Gonzalez’s study.
However, like corticosteroid injections, “the drawback of radiofrequency ablation is the fact that it only treats the symptoms and not the cause, and efficacy is usually limited over time,” she said.
Dr. Sconfienza said this study leaves her with three pertinent questions. “First, whether pain control extends beyond the 3-month follow-up reported by authors in the abstract; second, [what] is the efficacy of this method compared to other interventions (e.g., physical therapy, injections) or to doing nothing; and last, radiofrequency ablation is usually not a cheap treatment, thus a cost-efficacy analysis would be desirable, especially in comparison to other procedures.”
Dr. Gonzalez and Dr. Sconfienza have nothing relevant to disclose.
A version of this article originally appeared on Medscape.com.