User login
Risk of MACE Comparable Among Biologic Classes for Psoriasis, PsA
TOPLINE:
a database analysis finds.
METHODOLOGY:
- Data from the TriNetX health records database included 32,758 patients treated with TNF inhibitors (TNFi, 62.9%), interleukin-17 inhibitors (IL-17i, 15.4%), IL-23i (10.7%), and IL-12i/IL-23i (10.7%).
- The researchers calculated time-dependent risk for MACE using multinomial Cox proportional hazard ratios. The reference was TNFi exposure.
- Subset analyses compared MACE in patients with and without existing cardiovascular disease.
TAKEAWAY:
- Compared with TNFi use, there was no difference in the incidence of MACE events in the IL-17i, IL-23i, or IL-12i/IL-23i group.
- There were also no significant differences between biologic groups in the incidence of congestive heart failure, myocardial infarction, or cerebral vascular accident/stroke.
IN PRACTICE:
Despite some concern about increased risk for MACE with TNFi use, this study suggests no special risk for patients with psoriasis or PsA associated with TNFi vs other biologics. “Given our results, as it pertains to MACE, prescribers shouldn’t favor any one biologic class over another,” said lead investigator Shikha Singla, MD, medical director of the Psoriatic Arthritis Program at Medical College of Wisconsin in Milwaukee, Wisconsin.
SOURCE:
Bonit Gill, MD, a second-year fellow at Medical College of Wisconsin, presented the study as a poster at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
LIMITATIONS:
The study’s retrospective nature makes it impossible to prove causation and the patients included in the study were from Wisconsin, which may limit generalizability.
DISCLOSURES:
Dr. Gill had no relevant financial disclosures. Other study authors participated in trials or consulted for AbbVie, AstraZeneca, Novartis, Eli Lilly, Janssen, and UCB.
A version of this article first appeared on Medscape.com.
TOPLINE:
a database analysis finds.
METHODOLOGY:
- Data from the TriNetX health records database included 32,758 patients treated with TNF inhibitors (TNFi, 62.9%), interleukin-17 inhibitors (IL-17i, 15.4%), IL-23i (10.7%), and IL-12i/IL-23i (10.7%).
- The researchers calculated time-dependent risk for MACE using multinomial Cox proportional hazard ratios. The reference was TNFi exposure.
- Subset analyses compared MACE in patients with and without existing cardiovascular disease.
TAKEAWAY:
- Compared with TNFi use, there was no difference in the incidence of MACE events in the IL-17i, IL-23i, or IL-12i/IL-23i group.
- There were also no significant differences between biologic groups in the incidence of congestive heart failure, myocardial infarction, or cerebral vascular accident/stroke.
IN PRACTICE:
Despite some concern about increased risk for MACE with TNFi use, this study suggests no special risk for patients with psoriasis or PsA associated with TNFi vs other biologics. “Given our results, as it pertains to MACE, prescribers shouldn’t favor any one biologic class over another,” said lead investigator Shikha Singla, MD, medical director of the Psoriatic Arthritis Program at Medical College of Wisconsin in Milwaukee, Wisconsin.
SOURCE:
Bonit Gill, MD, a second-year fellow at Medical College of Wisconsin, presented the study as a poster at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
LIMITATIONS:
The study’s retrospective nature makes it impossible to prove causation and the patients included in the study were from Wisconsin, which may limit generalizability.
DISCLOSURES:
Dr. Gill had no relevant financial disclosures. Other study authors participated in trials or consulted for AbbVie, AstraZeneca, Novartis, Eli Lilly, Janssen, and UCB.
A version of this article first appeared on Medscape.com.
TOPLINE:
a database analysis finds.
METHODOLOGY:
- Data from the TriNetX health records database included 32,758 patients treated with TNF inhibitors (TNFi, 62.9%), interleukin-17 inhibitors (IL-17i, 15.4%), IL-23i (10.7%), and IL-12i/IL-23i (10.7%).
- The researchers calculated time-dependent risk for MACE using multinomial Cox proportional hazard ratios. The reference was TNFi exposure.
- Subset analyses compared MACE in patients with and without existing cardiovascular disease.
TAKEAWAY:
- Compared with TNFi use, there was no difference in the incidence of MACE events in the IL-17i, IL-23i, or IL-12i/IL-23i group.
- There were also no significant differences between biologic groups in the incidence of congestive heart failure, myocardial infarction, or cerebral vascular accident/stroke.
IN PRACTICE:
Despite some concern about increased risk for MACE with TNFi use, this study suggests no special risk for patients with psoriasis or PsA associated with TNFi vs other biologics. “Given our results, as it pertains to MACE, prescribers shouldn’t favor any one biologic class over another,” said lead investigator Shikha Singla, MD, medical director of the Psoriatic Arthritis Program at Medical College of Wisconsin in Milwaukee, Wisconsin.
SOURCE:
Bonit Gill, MD, a second-year fellow at Medical College of Wisconsin, presented the study as a poster at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
LIMITATIONS:
The study’s retrospective nature makes it impossible to prove causation and the patients included in the study were from Wisconsin, which may limit generalizability.
DISCLOSURES:
Dr. Gill had no relevant financial disclosures. Other study authors participated in trials or consulted for AbbVie, AstraZeneca, Novartis, Eli Lilly, Janssen, and UCB.
A version of this article first appeared on Medscape.com.
Commentary: IL-13 in PsA, PsA Risk, and Exercise, August 2024
Age at psoriasis onset may influence the risk of developing PsA. Cheemalavagu and colleagues aimed to identify clinical factors associated with PsA development in patients with psoriasis. Using data from a registry that included 384 patients diagnosed with PsA either after or concurrently with their psoriasis diagnosis, they demonstrated that patients with psoriasis onset at the age of 42.6 vs 18.9 years had a 62% shorter time interval between psoriasis and PsA diagnoses and were ~4.6 times more likely to have a concurrent onset of PsA within 6 months of having psoriasis. Thus, older age at onset of psoriasis may indicate a higher risk of developing PsA. This result is consistent with the observation that psoriasis patients carrying the human leukocyte antigen (HLA) C*06:02 allele (associated with early-onset psoriasis) are at lower risk of developing PsA.
Most patients with PsA have psoriasis vulgaris. The differential risk of PsA with different psoriasis phenotypes is less well studied. Therefore, Gershater and colleagues conducted a population-based retrospective cohort study that included patients with psoriasis vulgaris (n = 35,281), pustulosis palmoplantaris (n = 9639), or generalized pustular psoriasis (n = 2281), and who were propensity score–matched with an equal number of control individuals without psoriasis. They demonstrated that compared with control individuals without psoriasis, patients with psoriasis vulgaris had the highest risk for incident PsA (hazard ratio [HR] 87.7), followed by those with generalized pustular psoriasis (HR 26.8) and pustulosis palmoplantaris (HR 15.3). Thus, the study confirms the highest risk for PsA with psoriasis vulgaris, as well as the estimated risk for other, less common forms of psoriasis.
Finally, a cross-sectional study by Toledano and colleagues showed that PsA patients with a sedentary lifestyle (<90 min of physical activity per week) had more enthesitis, fatigue, pain, higher disease activity, greater disease impact, and lower functionality compared with those having a nonsedentary lifestyle. The study indicates that PsA patients would benefit from >90 minutes of physical activity per week.
Additional References
- Davies NM, Holmes MV, Davey Smith G. Reading Mendelian randomisation studies: A guide, glossary, and checklist for clinicians. BMJ. 2018;362:k601. doi: 10.1136/bmj.k601 Source
- Zhao H, Zhou Y, Wang Z, et al. Plasma proteins and psoriatic arthritis: A proteome-wide Mendelian randomization study. Front Immunol. 2024;15:1417564. doi: 10.3389/fimmu.2024.1417564 Source
Age at psoriasis onset may influence the risk of developing PsA. Cheemalavagu and colleagues aimed to identify clinical factors associated with PsA development in patients with psoriasis. Using data from a registry that included 384 patients diagnosed with PsA either after or concurrently with their psoriasis diagnosis, they demonstrated that patients with psoriasis onset at the age of 42.6 vs 18.9 years had a 62% shorter time interval between psoriasis and PsA diagnoses and were ~4.6 times more likely to have a concurrent onset of PsA within 6 months of having psoriasis. Thus, older age at onset of psoriasis may indicate a higher risk of developing PsA. This result is consistent with the observation that psoriasis patients carrying the human leukocyte antigen (HLA) C*06:02 allele (associated with early-onset psoriasis) are at lower risk of developing PsA.
Most patients with PsA have psoriasis vulgaris. The differential risk of PsA with different psoriasis phenotypes is less well studied. Therefore, Gershater and colleagues conducted a population-based retrospective cohort study that included patients with psoriasis vulgaris (n = 35,281), pustulosis palmoplantaris (n = 9639), or generalized pustular psoriasis (n = 2281), and who were propensity score–matched with an equal number of control individuals without psoriasis. They demonstrated that compared with control individuals without psoriasis, patients with psoriasis vulgaris had the highest risk for incident PsA (hazard ratio [HR] 87.7), followed by those with generalized pustular psoriasis (HR 26.8) and pustulosis palmoplantaris (HR 15.3). Thus, the study confirms the highest risk for PsA with psoriasis vulgaris, as well as the estimated risk for other, less common forms of psoriasis.
Finally, a cross-sectional study by Toledano and colleagues showed that PsA patients with a sedentary lifestyle (<90 min of physical activity per week) had more enthesitis, fatigue, pain, higher disease activity, greater disease impact, and lower functionality compared with those having a nonsedentary lifestyle. The study indicates that PsA patients would benefit from >90 minutes of physical activity per week.
Additional References
- Davies NM, Holmes MV, Davey Smith G. Reading Mendelian randomisation studies: A guide, glossary, and checklist for clinicians. BMJ. 2018;362:k601. doi: 10.1136/bmj.k601 Source
- Zhao H, Zhou Y, Wang Z, et al. Plasma proteins and psoriatic arthritis: A proteome-wide Mendelian randomization study. Front Immunol. 2024;15:1417564. doi: 10.3389/fimmu.2024.1417564 Source
Age at psoriasis onset may influence the risk of developing PsA. Cheemalavagu and colleagues aimed to identify clinical factors associated with PsA development in patients with psoriasis. Using data from a registry that included 384 patients diagnosed with PsA either after or concurrently with their psoriasis diagnosis, they demonstrated that patients with psoriasis onset at the age of 42.6 vs 18.9 years had a 62% shorter time interval between psoriasis and PsA diagnoses and were ~4.6 times more likely to have a concurrent onset of PsA within 6 months of having psoriasis. Thus, older age at onset of psoriasis may indicate a higher risk of developing PsA. This result is consistent with the observation that psoriasis patients carrying the human leukocyte antigen (HLA) C*06:02 allele (associated with early-onset psoriasis) are at lower risk of developing PsA.
Most patients with PsA have psoriasis vulgaris. The differential risk of PsA with different psoriasis phenotypes is less well studied. Therefore, Gershater and colleagues conducted a population-based retrospective cohort study that included patients with psoriasis vulgaris (n = 35,281), pustulosis palmoplantaris (n = 9639), or generalized pustular psoriasis (n = 2281), and who were propensity score–matched with an equal number of control individuals without psoriasis. They demonstrated that compared with control individuals without psoriasis, patients with psoriasis vulgaris had the highest risk for incident PsA (hazard ratio [HR] 87.7), followed by those with generalized pustular psoriasis (HR 26.8) and pustulosis palmoplantaris (HR 15.3). Thus, the study confirms the highest risk for PsA with psoriasis vulgaris, as well as the estimated risk for other, less common forms of psoriasis.
Finally, a cross-sectional study by Toledano and colleagues showed that PsA patients with a sedentary lifestyle (<90 min of physical activity per week) had more enthesitis, fatigue, pain, higher disease activity, greater disease impact, and lower functionality compared with those having a nonsedentary lifestyle. The study indicates that PsA patients would benefit from >90 minutes of physical activity per week.
Additional References
- Davies NM, Holmes MV, Davey Smith G. Reading Mendelian randomisation studies: A guide, glossary, and checklist for clinicians. BMJ. 2018;362:k601. doi: 10.1136/bmj.k601 Source
- Zhao H, Zhou Y, Wang Z, et al. Plasma proteins and psoriatic arthritis: A proteome-wide Mendelian randomization study. Front Immunol. 2024;15:1417564. doi: 10.3389/fimmu.2024.1417564 Source
Steroids’ 75th Anniversary: Clinicians Strive to Use Less
Now, 75 years after the first presentations were made on the “sensational” effects of cortisone in the treatment of rheumatoid arthritis (RA), glucocorticoids (GCs) are still highly relevant and widely used in the management of RA and other immune-mediated inflammatory diseases.
“It makes me smile because this is such an old drug, and we need it still so much. It still hasn’t been replaced,” Josef S. Smolen, MD, observed at annual European Congress of Rheumatology.
At low doses, GCs are highly effective as anti-inflammatory and anti-destructive agents in RA and many other diseases, said Dr. Smolen, a rheumatologist and immunologist and professor emeritus at the Medical University of Vienna, Austria.
But even after all this time, the mechanisms that lead to efficacy vs toxicity have yet to be clarified. “Such separation may provide further insights into future treatment options,” said Dr. Smolen.
His comments, made during a special session on the 75th anniversary of GCs at EULAR 2024, underscore the endless saga to manage GCs while finding better alternatives. Opinions differ on what the research says on toxicity and dosage and whether a long-term, low-dose option is viable. Alternative therapies are being studied, but those endeavors are still in the early stages of development.
While GCs are still used chronically in many patients, clinicians should always attempt to discontinue them whenever possible, Frank Buttgereit, MD, professor of rheumatology and deputy head of the Department of Rheumatology and Clinical Immunology at Charité – Universitätsmedizin Berlin, Germany, told attendees at the congress. Up to 60% of patients in registries use GCs, and many patients with early or established RA enter randomized controlled trials on GCs as maintenance therapy.
The ubiquity of GC usage stems in part from overprescribing by non-rheumatologist physicians who might not have access to or aren’t aware of newer biologics or disease-modifying antirheumatic drugs (DMARDs). “We see a lot of patients on long-term glucocorticoids, chronic use for years and years, decades of glucocorticoids,” said Giovanni Adami, MD, PhD, a rheumatologist at the University of Verona, Italy, who has coauthored several studies on the use of GCs.
Societies Agree: Discontinue as Fast as Possible
GCs have been associated with a long list of adverse events, most notably Cushing syndrome, hypertension, cardiovascular disease, osteoporosis, myopathy, peptic ulcer, adrenal insufficiency (AI), infections, mood disorders, ophthalmologic disorders such as cataracts, skin disorders, menstrual septic necrosis, and pancreatitis.
Dose matters, Dr. Smolen said, citing studies that found that cumulative GC doses of 1000 or 1100 mg increase risks. One study by German researchers found that doses above 10 mg/d significantly raised the hazard ratio for death.
Because high disease activity is also associated with an equally high mortality risk, “we have to balance this out: Active disease vs glucocorticoid use, especially in countries that have less access to modern therapies than we have in the more affluent Western regions,” Dr. Smolen said.
Rheumatology societies generally agree that clinicians should try to minimize GC use or eventually discontinue the therapy.
The American College of Rheumatology recommends not using GCs as part of the first-line treatment of RA. “And if you want to use [them], you should do that for less than 3 months, taper and discontinue as fast as possible, and use the lowest dose possible,” Dr. Adami said.
EULAR’s recommendation is more nuanced in that it allows for a lower dose but gives physicians more choice in how they want to handle GCs, Dr. Adami said. The task force added that all patients should try to taper down or discontinue as fast as possible, he said.
For GCs in the management of systemic lupus erythematosus, a EULAR task force recommended that the type and severity of organ involvement should determine dose, with a long-term goal of maintaining the dose < 5 mg/d or possibly withdrawing it.
EULAR also recommends GC bridging when initiating or changing conventional synthetic (cs) DMARDs. This effectively dismisses the use of GCs when using biologic DMARDs or targeted synthetic DMARDs. As a bridging therapy, EULAR recommends either a single parenteral dose of GC or a predefined tapering or discontinuation scheme within 3 months, when starting an oral GC.
Low-Dose Approach Gains Ground
While saying he’d be the first physician to eliminate GCs whenever possible, Dr. Buttgereit made the case before the EULAR Congress that GCs in low doses could still play a role in treatment.
Many physicians believe that very low doses between 2 and 4 mg/d are a realistic therapy option for RA, he said, adding that a mean daily usage < 5 mg could be used over a longer period with relatively low risk.
Several studies he coauthored tested the 5-mg approach. The GLORIA trial compared 5 mg/d prednisolone and placebo in 451 patients aged 65 years and older with active RA over the course of 2 years. The researchers found that patients on prednisolone had a mean Disease Activity Score in 28 joints (DAS28) that was 0.37 points lower and mean joint damage score that was 1.7 points lower than those of patients on placebo, suggesting that the GC had long-term benefits in these patients with RA.
The tradeoff was a 24% increase in the risk of having at least one adverse event of special interest, but most of these events were non-severe infections, Dr. Buttgereit said.
Another study, the SEMIRA trial, assigned 128 patients to a continued regimen of prednisone 5 mg/d for 24 weeks. Another group of 131 patients received a tapered-prednisone regimen. All patients received tocilizumab 162 mg with or without csDMARDs, maintained at stable doses.
Patients in the first cohort achieved superior disease activity control than those in the tapered regimen group. “The side effects showed that in the tapering prednisone group, there were more treatment-emergent adverse effects in this double-blind trial as compared to the continued prednisone group,” Dr. Buttgereit said.
One limitation of the SEMIRA trial was that it studied the effect of tocilizumab as a GC-sparing agent, and it didn’t consider using a tumor necrosis factor or Janus kinase (JAK) inhibitor, which might have a more potent effect on pain and GC dose reduction, Dr. Adami said. “Why do we need to use glucocorticoids if we know they might be detrimental, if we know there might be some other option in our armamentarium?”
Other studies have shown that low-dose GC protocols can be used with standard treatment, according to Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh School of Medicine.
“Examples of this are the LoVAS and PEXIVAS studies for antineutrophil cytoplasmic antibody-associated [ANCA] vasculitis. This has been highlighted in existing treatment recommendations for ANCA vasculitis and systemic lupus erythematosus nephritis,” Dr. Sattui said.
Two-year results from LoVAS showed noninferiority in remission induction rates and rates of relapse and significantly less frequent serious adverse events between a reduced-dose GC regimen at 0.5 mg/kg/d and conventional high-dose GC regimen at 1 mg/kg/d plus rituximab for ANCA vasculitis.
PEXIVAS demonstrated the noninferiority of a reduced-dose regimen of GCs vs a standard-dose regimen with respect to death or end-stage kidney disease in patients with severe disease involvement.
Debating the Toxicity Threshold
Are low GC dosages significantly associated with adverse events like mortality, cardiovascular, or diabetes risk? It depends on who you ask.
Much of the toxicity data on GCs come from inadequately powered or controlled studies and often refer to doses that currently are considered too high, Dr. Buttgereit said. His presentation highlighted a study from Hong Kong, a time-varying analysis of GC dose and incident risk for major adverse cardiovascular events (MACE) in more than 12,000 patients with RA. Researchers found that GC regimens ≥ 5 mg/d significantly increased the risk for MACE. Comparatively, doses below this threshold did not confer excessive risk, he said.
Low-dose GCs are lesser toxic than high-dose GCs, noted Joan Merrill, MD, a professor with the Arthritis and Clinical Immunology Research Program at The University of Oklahoma Health Sciences Center, Oklahoma City. “There may be less weight gain, less chance of acne, and less risk for all the slower, more organ-threatening side effects.”
Dr. Merrill, who cares for patients with lupus, said physicians can keep lupus in check for years, using constant, low-dose GCs. “The one thing we know is that steroids work.” But over many years, damage may still occur, she cautioned.
But even a low dose could present health problems to patients. The GLORIA trial of patients with RA, which showed promising results on disease control with 5 mg/d, found an association between GCs and increased risk for infection and osteoporosis. There was a higher overall risk for adverse events related to skin, infections, and bone mineral density changes. Bone mineral density loss and fractures were more common in the GC group, Adami noted.
Surprisingly, some of the trial’s authors said patients could handle such adverse events. But what is your threshold of “acceptable?” Dr. Adami asked.
Other studies have found associations between low-dose GC regimens and adverse events. Researchers of a 2023 study reported bone mineral density loss in patients with inflammatory rheumatic musculoskeletal diseases on a 2.5-mg/d regimen. Another decade-long analysis of Medicare and Optum data found a link between serious infection and low-dose GCs in patients receiving stable DMARD therapy. Investigators reported risk even at daily doses of ≤ 5 mg.
Dr. Adami acknowledged that these studies may have “confounding by indication,” a channeling bias in which people with severe RA are more likely to be treated with GCs. For this reason, it’s a challenge to disentangle the independent role of GCs from the disease activity itself, he said.
The big question is: Why don’t these observational studies show an increased risk for adverse events with biologic drugs that are given to more severe patients? “That confirms the hypothesis that confounding by indication for GCs is minimal, and most of the risk is driven by GCs,” he said.
Tapering Options Across Diseases
Rheumatologists in the field continue to navigate GC-tapering options and treatment combinations that reduce the cumulative use of GCs over time, finding their own solutions based on the conditions they treat.
In his EULAR presentation, Dr. Buttgereit suggested that current therapeutic approaches for RA may be too narrow when they don’t consider the possibility of including very low doses of GCs.
For RA, “why shouldn’t we not do a combination of something like methotrexate plus a JAK inhibitor or a biological,” plus a very low dose of GCs < 5 mg/d, he asked.
However, Dr. Adami said he generally avoids GCs if RA disease activity is not severe (based on DAS28) and if the patient has a visual analog scale pain score < 7. “Nonetheless, even in patients with more severe disease, I would avoid GCs for more than 3 months. Usually, 1 month of steroids, tapered rapidly and discontinued.”
All patients should receive an appropriate treat-to-target strategy with csDMARDs and biologics if needed, he added.
A patient coming to clinic with difficult-to-treat RA who chronically uses GCs deserves special attention. The priority is bone protection with an anti-osteoporosis medication. “I found that JAK inhibitors, in some cases, help with the discontinuation of steroids, especially in those with residual pain. Therefore, I would think of switching medication,” Dr. Adami said.
For polymyalgia rheumatica, most clinicians will likely try to taper GCs around 52 weeks, similar to ACR/EULAR guidelines, according to Robert F. Spiera, MD, director of the Scleroderma and Vasculitis Program at Hospital for Special Surgery, New York City.
“I usually challenge patients with a more rapid taper, hoping to get them off GCs in 6 or even 4 months in some patients, recognizing that many will flare, and we will have to bump up their GC dose,” Dr. Spiera said.
For patients with lupus, GCs remain the most effective treatment, Dr. Merrill said. “The toxicities are unacceptable for long-term use. So we try to get in fast when we need them and get out as soon as possible after that, tapering down as fast as the patient can tolerate it.”
Unfortunately, that’s not always as fast as the clinician or patient hopes for, she said.
“New treatments are being developed that may help us avoid the constant use of steroids. However, it would be wonderful to see how these new safer types of steroids work in lupus,” she said.
Minimizing GCs is an important goal that should be considered and aimed for in every single patient, Dr. Sattui said. “Risk of GC toxicity should be considered in all patients, assessing [them] for cardiometabolic comorbidities, bone metabolic diseases, risk of infection, among many others.” Sticking to one specific GC-tapering protocol might not be achievable for every patient, however, based on disease characteristics, response, and other factors, he added.
Monitoring for GC toxicity is important and should occur during and after every single clinical visit, he emphasized. Patient education is critical. “Different tools have been developed and employed in clinical trials, both patient- and physician-facing instruments. Implementation to clinical practice of some of these should be the next step in order to achieve a more systematic approach.”
What to Consider for AI Symptoms
Clinicians also need to address AI in patients who are coming off GCs, Dr. Sattui said. He advised that symptoms suggestive of AI, including malaise, fatigue, nausea, and muscle and/or joint pain, should guide testing.
Even in the absence of symptoms, clinicians should consider assessing patients who have been on high doses for prolonged periods or obese or older adults who might be at a high risk for AI. “Signs to consider include weight loss, hypotension, or orthostatism,” he said.
Differentiating between AI symptoms and symptoms from the underlying disease can be a challenge. This requires a physical exam and workup, including morning serum cortisol. Collaboration with endocrinology colleagues and other treating providers is important, as well as patient education of symptoms and monitoring for possible adjustments in treating AI and other acute diseases, he said.
Dr. Smolen received research grants from AbbVie, AstraZeneca, Galapagos, and Eli Lilly. Dr. Adami received speaker fees and/or was a consultant for Galapagos, Theramex, Amgen, Eli Lilly, UCB, Fresenius Kabi, Bristol Myers Squibb, Abiogen, and Pfizer. Dr. Buttgereit’s disclosures included AbbVie, AstraZeneca, Grünenthal, Horizon Therapeutics, Mundipharma, Pfizer, and Roche. Dr. Merrill had no relevant disclosures. Dr. Spiera has been a consultant for Roche-Genentech, GlaxoSmithKline, Sanofi, ChemoCentryx, Novartis, Galderma, Cytori, AstraZeneca, Amgen, and AbbVie and received research grant support from GlaxoSmithKline, Roche-Genentech, AstraZeneca, Bristol Myers Squibb, Kadmon, Boehringer Ingelheim, Cytori, ChemoCentryx, Corbus, Novartis, Amgen, and AbbVie. Dr. Sattui reported receiving research support from AstraZeneca and GlaxoSmithKline (clinical trials), receiving consulting fees from Sanofi (funds toward research support), serving on advisory boards for Sanofi and Amgen (funds toward research support), and receiving speaker fees from Fresenius Kabi (funds toward research support).
A version of this article appeared on Medscape.com.
Now, 75 years after the first presentations were made on the “sensational” effects of cortisone in the treatment of rheumatoid arthritis (RA), glucocorticoids (GCs) are still highly relevant and widely used in the management of RA and other immune-mediated inflammatory diseases.
“It makes me smile because this is such an old drug, and we need it still so much. It still hasn’t been replaced,” Josef S. Smolen, MD, observed at annual European Congress of Rheumatology.
At low doses, GCs are highly effective as anti-inflammatory and anti-destructive agents in RA and many other diseases, said Dr. Smolen, a rheumatologist and immunologist and professor emeritus at the Medical University of Vienna, Austria.
But even after all this time, the mechanisms that lead to efficacy vs toxicity have yet to be clarified. “Such separation may provide further insights into future treatment options,” said Dr. Smolen.
His comments, made during a special session on the 75th anniversary of GCs at EULAR 2024, underscore the endless saga to manage GCs while finding better alternatives. Opinions differ on what the research says on toxicity and dosage and whether a long-term, low-dose option is viable. Alternative therapies are being studied, but those endeavors are still in the early stages of development.
While GCs are still used chronically in many patients, clinicians should always attempt to discontinue them whenever possible, Frank Buttgereit, MD, professor of rheumatology and deputy head of the Department of Rheumatology and Clinical Immunology at Charité – Universitätsmedizin Berlin, Germany, told attendees at the congress. Up to 60% of patients in registries use GCs, and many patients with early or established RA enter randomized controlled trials on GCs as maintenance therapy.
The ubiquity of GC usage stems in part from overprescribing by non-rheumatologist physicians who might not have access to or aren’t aware of newer biologics or disease-modifying antirheumatic drugs (DMARDs). “We see a lot of patients on long-term glucocorticoids, chronic use for years and years, decades of glucocorticoids,” said Giovanni Adami, MD, PhD, a rheumatologist at the University of Verona, Italy, who has coauthored several studies on the use of GCs.
Societies Agree: Discontinue as Fast as Possible
GCs have been associated with a long list of adverse events, most notably Cushing syndrome, hypertension, cardiovascular disease, osteoporosis, myopathy, peptic ulcer, adrenal insufficiency (AI), infections, mood disorders, ophthalmologic disorders such as cataracts, skin disorders, menstrual septic necrosis, and pancreatitis.
Dose matters, Dr. Smolen said, citing studies that found that cumulative GC doses of 1000 or 1100 mg increase risks. One study by German researchers found that doses above 10 mg/d significantly raised the hazard ratio for death.
Because high disease activity is also associated with an equally high mortality risk, “we have to balance this out: Active disease vs glucocorticoid use, especially in countries that have less access to modern therapies than we have in the more affluent Western regions,” Dr. Smolen said.
Rheumatology societies generally agree that clinicians should try to minimize GC use or eventually discontinue the therapy.
The American College of Rheumatology recommends not using GCs as part of the first-line treatment of RA. “And if you want to use [them], you should do that for less than 3 months, taper and discontinue as fast as possible, and use the lowest dose possible,” Dr. Adami said.
EULAR’s recommendation is more nuanced in that it allows for a lower dose but gives physicians more choice in how they want to handle GCs, Dr. Adami said. The task force added that all patients should try to taper down or discontinue as fast as possible, he said.
For GCs in the management of systemic lupus erythematosus, a EULAR task force recommended that the type and severity of organ involvement should determine dose, with a long-term goal of maintaining the dose < 5 mg/d or possibly withdrawing it.
EULAR also recommends GC bridging when initiating or changing conventional synthetic (cs) DMARDs. This effectively dismisses the use of GCs when using biologic DMARDs or targeted synthetic DMARDs. As a bridging therapy, EULAR recommends either a single parenteral dose of GC or a predefined tapering or discontinuation scheme within 3 months, when starting an oral GC.
Low-Dose Approach Gains Ground
While saying he’d be the first physician to eliminate GCs whenever possible, Dr. Buttgereit made the case before the EULAR Congress that GCs in low doses could still play a role in treatment.
Many physicians believe that very low doses between 2 and 4 mg/d are a realistic therapy option for RA, he said, adding that a mean daily usage < 5 mg could be used over a longer period with relatively low risk.
Several studies he coauthored tested the 5-mg approach. The GLORIA trial compared 5 mg/d prednisolone and placebo in 451 patients aged 65 years and older with active RA over the course of 2 years. The researchers found that patients on prednisolone had a mean Disease Activity Score in 28 joints (DAS28) that was 0.37 points lower and mean joint damage score that was 1.7 points lower than those of patients on placebo, suggesting that the GC had long-term benefits in these patients with RA.
The tradeoff was a 24% increase in the risk of having at least one adverse event of special interest, but most of these events were non-severe infections, Dr. Buttgereit said.
Another study, the SEMIRA trial, assigned 128 patients to a continued regimen of prednisone 5 mg/d for 24 weeks. Another group of 131 patients received a tapered-prednisone regimen. All patients received tocilizumab 162 mg with or without csDMARDs, maintained at stable doses.
Patients in the first cohort achieved superior disease activity control than those in the tapered regimen group. “The side effects showed that in the tapering prednisone group, there were more treatment-emergent adverse effects in this double-blind trial as compared to the continued prednisone group,” Dr. Buttgereit said.
One limitation of the SEMIRA trial was that it studied the effect of tocilizumab as a GC-sparing agent, and it didn’t consider using a tumor necrosis factor or Janus kinase (JAK) inhibitor, which might have a more potent effect on pain and GC dose reduction, Dr. Adami said. “Why do we need to use glucocorticoids if we know they might be detrimental, if we know there might be some other option in our armamentarium?”
Other studies have shown that low-dose GC protocols can be used with standard treatment, according to Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh School of Medicine.
“Examples of this are the LoVAS and PEXIVAS studies for antineutrophil cytoplasmic antibody-associated [ANCA] vasculitis. This has been highlighted in existing treatment recommendations for ANCA vasculitis and systemic lupus erythematosus nephritis,” Dr. Sattui said.
Two-year results from LoVAS showed noninferiority in remission induction rates and rates of relapse and significantly less frequent serious adverse events between a reduced-dose GC regimen at 0.5 mg/kg/d and conventional high-dose GC regimen at 1 mg/kg/d plus rituximab for ANCA vasculitis.
PEXIVAS demonstrated the noninferiority of a reduced-dose regimen of GCs vs a standard-dose regimen with respect to death or end-stage kidney disease in patients with severe disease involvement.
Debating the Toxicity Threshold
Are low GC dosages significantly associated with adverse events like mortality, cardiovascular, or diabetes risk? It depends on who you ask.
Much of the toxicity data on GCs come from inadequately powered or controlled studies and often refer to doses that currently are considered too high, Dr. Buttgereit said. His presentation highlighted a study from Hong Kong, a time-varying analysis of GC dose and incident risk for major adverse cardiovascular events (MACE) in more than 12,000 patients with RA. Researchers found that GC regimens ≥ 5 mg/d significantly increased the risk for MACE. Comparatively, doses below this threshold did not confer excessive risk, he said.
Low-dose GCs are lesser toxic than high-dose GCs, noted Joan Merrill, MD, a professor with the Arthritis and Clinical Immunology Research Program at The University of Oklahoma Health Sciences Center, Oklahoma City. “There may be less weight gain, less chance of acne, and less risk for all the slower, more organ-threatening side effects.”
Dr. Merrill, who cares for patients with lupus, said physicians can keep lupus in check for years, using constant, low-dose GCs. “The one thing we know is that steroids work.” But over many years, damage may still occur, she cautioned.
But even a low dose could present health problems to patients. The GLORIA trial of patients with RA, which showed promising results on disease control with 5 mg/d, found an association between GCs and increased risk for infection and osteoporosis. There was a higher overall risk for adverse events related to skin, infections, and bone mineral density changes. Bone mineral density loss and fractures were more common in the GC group, Adami noted.
Surprisingly, some of the trial’s authors said patients could handle such adverse events. But what is your threshold of “acceptable?” Dr. Adami asked.
Other studies have found associations between low-dose GC regimens and adverse events. Researchers of a 2023 study reported bone mineral density loss in patients with inflammatory rheumatic musculoskeletal diseases on a 2.5-mg/d regimen. Another decade-long analysis of Medicare and Optum data found a link between serious infection and low-dose GCs in patients receiving stable DMARD therapy. Investigators reported risk even at daily doses of ≤ 5 mg.
Dr. Adami acknowledged that these studies may have “confounding by indication,” a channeling bias in which people with severe RA are more likely to be treated with GCs. For this reason, it’s a challenge to disentangle the independent role of GCs from the disease activity itself, he said.
The big question is: Why don’t these observational studies show an increased risk for adverse events with biologic drugs that are given to more severe patients? “That confirms the hypothesis that confounding by indication for GCs is minimal, and most of the risk is driven by GCs,” he said.
Tapering Options Across Diseases
Rheumatologists in the field continue to navigate GC-tapering options and treatment combinations that reduce the cumulative use of GCs over time, finding their own solutions based on the conditions they treat.
In his EULAR presentation, Dr. Buttgereit suggested that current therapeutic approaches for RA may be too narrow when they don’t consider the possibility of including very low doses of GCs.
For RA, “why shouldn’t we not do a combination of something like methotrexate plus a JAK inhibitor or a biological,” plus a very low dose of GCs < 5 mg/d, he asked.
However, Dr. Adami said he generally avoids GCs if RA disease activity is not severe (based on DAS28) and if the patient has a visual analog scale pain score < 7. “Nonetheless, even in patients with more severe disease, I would avoid GCs for more than 3 months. Usually, 1 month of steroids, tapered rapidly and discontinued.”
All patients should receive an appropriate treat-to-target strategy with csDMARDs and biologics if needed, he added.
A patient coming to clinic with difficult-to-treat RA who chronically uses GCs deserves special attention. The priority is bone protection with an anti-osteoporosis medication. “I found that JAK inhibitors, in some cases, help with the discontinuation of steroids, especially in those with residual pain. Therefore, I would think of switching medication,” Dr. Adami said.
For polymyalgia rheumatica, most clinicians will likely try to taper GCs around 52 weeks, similar to ACR/EULAR guidelines, according to Robert F. Spiera, MD, director of the Scleroderma and Vasculitis Program at Hospital for Special Surgery, New York City.
“I usually challenge patients with a more rapid taper, hoping to get them off GCs in 6 or even 4 months in some patients, recognizing that many will flare, and we will have to bump up their GC dose,” Dr. Spiera said.
For patients with lupus, GCs remain the most effective treatment, Dr. Merrill said. “The toxicities are unacceptable for long-term use. So we try to get in fast when we need them and get out as soon as possible after that, tapering down as fast as the patient can tolerate it.”
Unfortunately, that’s not always as fast as the clinician or patient hopes for, she said.
“New treatments are being developed that may help us avoid the constant use of steroids. However, it would be wonderful to see how these new safer types of steroids work in lupus,” she said.
Minimizing GCs is an important goal that should be considered and aimed for in every single patient, Dr. Sattui said. “Risk of GC toxicity should be considered in all patients, assessing [them] for cardiometabolic comorbidities, bone metabolic diseases, risk of infection, among many others.” Sticking to one specific GC-tapering protocol might not be achievable for every patient, however, based on disease characteristics, response, and other factors, he added.
Monitoring for GC toxicity is important and should occur during and after every single clinical visit, he emphasized. Patient education is critical. “Different tools have been developed and employed in clinical trials, both patient- and physician-facing instruments. Implementation to clinical practice of some of these should be the next step in order to achieve a more systematic approach.”
What to Consider for AI Symptoms
Clinicians also need to address AI in patients who are coming off GCs, Dr. Sattui said. He advised that symptoms suggestive of AI, including malaise, fatigue, nausea, and muscle and/or joint pain, should guide testing.
Even in the absence of symptoms, clinicians should consider assessing patients who have been on high doses for prolonged periods or obese or older adults who might be at a high risk for AI. “Signs to consider include weight loss, hypotension, or orthostatism,” he said.
Differentiating between AI symptoms and symptoms from the underlying disease can be a challenge. This requires a physical exam and workup, including morning serum cortisol. Collaboration with endocrinology colleagues and other treating providers is important, as well as patient education of symptoms and monitoring for possible adjustments in treating AI and other acute diseases, he said.
Dr. Smolen received research grants from AbbVie, AstraZeneca, Galapagos, and Eli Lilly. Dr. Adami received speaker fees and/or was a consultant for Galapagos, Theramex, Amgen, Eli Lilly, UCB, Fresenius Kabi, Bristol Myers Squibb, Abiogen, and Pfizer. Dr. Buttgereit’s disclosures included AbbVie, AstraZeneca, Grünenthal, Horizon Therapeutics, Mundipharma, Pfizer, and Roche. Dr. Merrill had no relevant disclosures. Dr. Spiera has been a consultant for Roche-Genentech, GlaxoSmithKline, Sanofi, ChemoCentryx, Novartis, Galderma, Cytori, AstraZeneca, Amgen, and AbbVie and received research grant support from GlaxoSmithKline, Roche-Genentech, AstraZeneca, Bristol Myers Squibb, Kadmon, Boehringer Ingelheim, Cytori, ChemoCentryx, Corbus, Novartis, Amgen, and AbbVie. Dr. Sattui reported receiving research support from AstraZeneca and GlaxoSmithKline (clinical trials), receiving consulting fees from Sanofi (funds toward research support), serving on advisory boards for Sanofi and Amgen (funds toward research support), and receiving speaker fees from Fresenius Kabi (funds toward research support).
A version of this article appeared on Medscape.com.
Now, 75 years after the first presentations were made on the “sensational” effects of cortisone in the treatment of rheumatoid arthritis (RA), glucocorticoids (GCs) are still highly relevant and widely used in the management of RA and other immune-mediated inflammatory diseases.
“It makes me smile because this is such an old drug, and we need it still so much. It still hasn’t been replaced,” Josef S. Smolen, MD, observed at annual European Congress of Rheumatology.
At low doses, GCs are highly effective as anti-inflammatory and anti-destructive agents in RA and many other diseases, said Dr. Smolen, a rheumatologist and immunologist and professor emeritus at the Medical University of Vienna, Austria.
But even after all this time, the mechanisms that lead to efficacy vs toxicity have yet to be clarified. “Such separation may provide further insights into future treatment options,” said Dr. Smolen.
His comments, made during a special session on the 75th anniversary of GCs at EULAR 2024, underscore the endless saga to manage GCs while finding better alternatives. Opinions differ on what the research says on toxicity and dosage and whether a long-term, low-dose option is viable. Alternative therapies are being studied, but those endeavors are still in the early stages of development.
While GCs are still used chronically in many patients, clinicians should always attempt to discontinue them whenever possible, Frank Buttgereit, MD, professor of rheumatology and deputy head of the Department of Rheumatology and Clinical Immunology at Charité – Universitätsmedizin Berlin, Germany, told attendees at the congress. Up to 60% of patients in registries use GCs, and many patients with early or established RA enter randomized controlled trials on GCs as maintenance therapy.
The ubiquity of GC usage stems in part from overprescribing by non-rheumatologist physicians who might not have access to or aren’t aware of newer biologics or disease-modifying antirheumatic drugs (DMARDs). “We see a lot of patients on long-term glucocorticoids, chronic use for years and years, decades of glucocorticoids,” said Giovanni Adami, MD, PhD, a rheumatologist at the University of Verona, Italy, who has coauthored several studies on the use of GCs.
Societies Agree: Discontinue as Fast as Possible
GCs have been associated with a long list of adverse events, most notably Cushing syndrome, hypertension, cardiovascular disease, osteoporosis, myopathy, peptic ulcer, adrenal insufficiency (AI), infections, mood disorders, ophthalmologic disorders such as cataracts, skin disorders, menstrual septic necrosis, and pancreatitis.
Dose matters, Dr. Smolen said, citing studies that found that cumulative GC doses of 1000 or 1100 mg increase risks. One study by German researchers found that doses above 10 mg/d significantly raised the hazard ratio for death.
Because high disease activity is also associated with an equally high mortality risk, “we have to balance this out: Active disease vs glucocorticoid use, especially in countries that have less access to modern therapies than we have in the more affluent Western regions,” Dr. Smolen said.
Rheumatology societies generally agree that clinicians should try to minimize GC use or eventually discontinue the therapy.
The American College of Rheumatology recommends not using GCs as part of the first-line treatment of RA. “And if you want to use [them], you should do that for less than 3 months, taper and discontinue as fast as possible, and use the lowest dose possible,” Dr. Adami said.
EULAR’s recommendation is more nuanced in that it allows for a lower dose but gives physicians more choice in how they want to handle GCs, Dr. Adami said. The task force added that all patients should try to taper down or discontinue as fast as possible, he said.
For GCs in the management of systemic lupus erythematosus, a EULAR task force recommended that the type and severity of organ involvement should determine dose, with a long-term goal of maintaining the dose < 5 mg/d or possibly withdrawing it.
EULAR also recommends GC bridging when initiating or changing conventional synthetic (cs) DMARDs. This effectively dismisses the use of GCs when using biologic DMARDs or targeted synthetic DMARDs. As a bridging therapy, EULAR recommends either a single parenteral dose of GC or a predefined tapering or discontinuation scheme within 3 months, when starting an oral GC.
Low-Dose Approach Gains Ground
While saying he’d be the first physician to eliminate GCs whenever possible, Dr. Buttgereit made the case before the EULAR Congress that GCs in low doses could still play a role in treatment.
Many physicians believe that very low doses between 2 and 4 mg/d are a realistic therapy option for RA, he said, adding that a mean daily usage < 5 mg could be used over a longer period with relatively low risk.
Several studies he coauthored tested the 5-mg approach. The GLORIA trial compared 5 mg/d prednisolone and placebo in 451 patients aged 65 years and older with active RA over the course of 2 years. The researchers found that patients on prednisolone had a mean Disease Activity Score in 28 joints (DAS28) that was 0.37 points lower and mean joint damage score that was 1.7 points lower than those of patients on placebo, suggesting that the GC had long-term benefits in these patients with RA.
The tradeoff was a 24% increase in the risk of having at least one adverse event of special interest, but most of these events were non-severe infections, Dr. Buttgereit said.
Another study, the SEMIRA trial, assigned 128 patients to a continued regimen of prednisone 5 mg/d for 24 weeks. Another group of 131 patients received a tapered-prednisone regimen. All patients received tocilizumab 162 mg with or without csDMARDs, maintained at stable doses.
Patients in the first cohort achieved superior disease activity control than those in the tapered regimen group. “The side effects showed that in the tapering prednisone group, there were more treatment-emergent adverse effects in this double-blind trial as compared to the continued prednisone group,” Dr. Buttgereit said.
One limitation of the SEMIRA trial was that it studied the effect of tocilizumab as a GC-sparing agent, and it didn’t consider using a tumor necrosis factor or Janus kinase (JAK) inhibitor, which might have a more potent effect on pain and GC dose reduction, Dr. Adami said. “Why do we need to use glucocorticoids if we know they might be detrimental, if we know there might be some other option in our armamentarium?”
Other studies have shown that low-dose GC protocols can be used with standard treatment, according to Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh School of Medicine.
“Examples of this are the LoVAS and PEXIVAS studies for antineutrophil cytoplasmic antibody-associated [ANCA] vasculitis. This has been highlighted in existing treatment recommendations for ANCA vasculitis and systemic lupus erythematosus nephritis,” Dr. Sattui said.
Two-year results from LoVAS showed noninferiority in remission induction rates and rates of relapse and significantly less frequent serious adverse events between a reduced-dose GC regimen at 0.5 mg/kg/d and conventional high-dose GC regimen at 1 mg/kg/d plus rituximab for ANCA vasculitis.
PEXIVAS demonstrated the noninferiority of a reduced-dose regimen of GCs vs a standard-dose regimen with respect to death or end-stage kidney disease in patients with severe disease involvement.
Debating the Toxicity Threshold
Are low GC dosages significantly associated with adverse events like mortality, cardiovascular, or diabetes risk? It depends on who you ask.
Much of the toxicity data on GCs come from inadequately powered or controlled studies and often refer to doses that currently are considered too high, Dr. Buttgereit said. His presentation highlighted a study from Hong Kong, a time-varying analysis of GC dose and incident risk for major adverse cardiovascular events (MACE) in more than 12,000 patients with RA. Researchers found that GC regimens ≥ 5 mg/d significantly increased the risk for MACE. Comparatively, doses below this threshold did not confer excessive risk, he said.
Low-dose GCs are lesser toxic than high-dose GCs, noted Joan Merrill, MD, a professor with the Arthritis and Clinical Immunology Research Program at The University of Oklahoma Health Sciences Center, Oklahoma City. “There may be less weight gain, less chance of acne, and less risk for all the slower, more organ-threatening side effects.”
Dr. Merrill, who cares for patients with lupus, said physicians can keep lupus in check for years, using constant, low-dose GCs. “The one thing we know is that steroids work.” But over many years, damage may still occur, she cautioned.
But even a low dose could present health problems to patients. The GLORIA trial of patients with RA, which showed promising results on disease control with 5 mg/d, found an association between GCs and increased risk for infection and osteoporosis. There was a higher overall risk for adverse events related to skin, infections, and bone mineral density changes. Bone mineral density loss and fractures were more common in the GC group, Adami noted.
Surprisingly, some of the trial’s authors said patients could handle such adverse events. But what is your threshold of “acceptable?” Dr. Adami asked.
Other studies have found associations between low-dose GC regimens and adverse events. Researchers of a 2023 study reported bone mineral density loss in patients with inflammatory rheumatic musculoskeletal diseases on a 2.5-mg/d regimen. Another decade-long analysis of Medicare and Optum data found a link between serious infection and low-dose GCs in patients receiving stable DMARD therapy. Investigators reported risk even at daily doses of ≤ 5 mg.
Dr. Adami acknowledged that these studies may have “confounding by indication,” a channeling bias in which people with severe RA are more likely to be treated with GCs. For this reason, it’s a challenge to disentangle the independent role of GCs from the disease activity itself, he said.
The big question is: Why don’t these observational studies show an increased risk for adverse events with biologic drugs that are given to more severe patients? “That confirms the hypothesis that confounding by indication for GCs is minimal, and most of the risk is driven by GCs,” he said.
Tapering Options Across Diseases
Rheumatologists in the field continue to navigate GC-tapering options and treatment combinations that reduce the cumulative use of GCs over time, finding their own solutions based on the conditions they treat.
In his EULAR presentation, Dr. Buttgereit suggested that current therapeutic approaches for RA may be too narrow when they don’t consider the possibility of including very low doses of GCs.
For RA, “why shouldn’t we not do a combination of something like methotrexate plus a JAK inhibitor or a biological,” plus a very low dose of GCs < 5 mg/d, he asked.
However, Dr. Adami said he generally avoids GCs if RA disease activity is not severe (based on DAS28) and if the patient has a visual analog scale pain score < 7. “Nonetheless, even in patients with more severe disease, I would avoid GCs for more than 3 months. Usually, 1 month of steroids, tapered rapidly and discontinued.”
All patients should receive an appropriate treat-to-target strategy with csDMARDs and biologics if needed, he added.
A patient coming to clinic with difficult-to-treat RA who chronically uses GCs deserves special attention. The priority is bone protection with an anti-osteoporosis medication. “I found that JAK inhibitors, in some cases, help with the discontinuation of steroids, especially in those with residual pain. Therefore, I would think of switching medication,” Dr. Adami said.
For polymyalgia rheumatica, most clinicians will likely try to taper GCs around 52 weeks, similar to ACR/EULAR guidelines, according to Robert F. Spiera, MD, director of the Scleroderma and Vasculitis Program at Hospital for Special Surgery, New York City.
“I usually challenge patients with a more rapid taper, hoping to get them off GCs in 6 or even 4 months in some patients, recognizing that many will flare, and we will have to bump up their GC dose,” Dr. Spiera said.
For patients with lupus, GCs remain the most effective treatment, Dr. Merrill said. “The toxicities are unacceptable for long-term use. So we try to get in fast when we need them and get out as soon as possible after that, tapering down as fast as the patient can tolerate it.”
Unfortunately, that’s not always as fast as the clinician or patient hopes for, she said.
“New treatments are being developed that may help us avoid the constant use of steroids. However, it would be wonderful to see how these new safer types of steroids work in lupus,” she said.
Minimizing GCs is an important goal that should be considered and aimed for in every single patient, Dr. Sattui said. “Risk of GC toxicity should be considered in all patients, assessing [them] for cardiometabolic comorbidities, bone metabolic diseases, risk of infection, among many others.” Sticking to one specific GC-tapering protocol might not be achievable for every patient, however, based on disease characteristics, response, and other factors, he added.
Monitoring for GC toxicity is important and should occur during and after every single clinical visit, he emphasized. Patient education is critical. “Different tools have been developed and employed in clinical trials, both patient- and physician-facing instruments. Implementation to clinical practice of some of these should be the next step in order to achieve a more systematic approach.”
What to Consider for AI Symptoms
Clinicians also need to address AI in patients who are coming off GCs, Dr. Sattui said. He advised that symptoms suggestive of AI, including malaise, fatigue, nausea, and muscle and/or joint pain, should guide testing.
Even in the absence of symptoms, clinicians should consider assessing patients who have been on high doses for prolonged periods or obese or older adults who might be at a high risk for AI. “Signs to consider include weight loss, hypotension, or orthostatism,” he said.
Differentiating between AI symptoms and symptoms from the underlying disease can be a challenge. This requires a physical exam and workup, including morning serum cortisol. Collaboration with endocrinology colleagues and other treating providers is important, as well as patient education of symptoms and monitoring for possible adjustments in treating AI and other acute diseases, he said.
Dr. Smolen received research grants from AbbVie, AstraZeneca, Galapagos, and Eli Lilly. Dr. Adami received speaker fees and/or was a consultant for Galapagos, Theramex, Amgen, Eli Lilly, UCB, Fresenius Kabi, Bristol Myers Squibb, Abiogen, and Pfizer. Dr. Buttgereit’s disclosures included AbbVie, AstraZeneca, Grünenthal, Horizon Therapeutics, Mundipharma, Pfizer, and Roche. Dr. Merrill had no relevant disclosures. Dr. Spiera has been a consultant for Roche-Genentech, GlaxoSmithKline, Sanofi, ChemoCentryx, Novartis, Galderma, Cytori, AstraZeneca, Amgen, and AbbVie and received research grant support from GlaxoSmithKline, Roche-Genentech, AstraZeneca, Bristol Myers Squibb, Kadmon, Boehringer Ingelheim, Cytori, ChemoCentryx, Corbus, Novartis, Amgen, and AbbVie. Dr. Sattui reported receiving research support from AstraZeneca and GlaxoSmithKline (clinical trials), receiving consulting fees from Sanofi (funds toward research support), serving on advisory boards for Sanofi and Amgen (funds toward research support), and receiving speaker fees from Fresenius Kabi (funds toward research support).
A version of this article appeared on Medscape.com.
FROM EULAR 2024
Mysteries Persist About Tissue Resident Memory T Cells in Psoriasis
SEATTLE — In fact, flare-ups often recur at the same site, a phenomenon that might be driven by these resident memory cells, according to Liv Eidsmo, MD, PhD.
This has led to their use as biomarkers in clinical trials for new therapies, but TRM T cells have a complex biology that is far from fully understood, Dr. Eidsmo said at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. “With time, we’re understanding that the regulation of the functionality is more complicated than we thought, so following these cells as a positive outcome of a clinical trial is a little bit premature,” said Dr. Eidsmo, who is a consultant dermatologist at the University of Copenhagen, Copenhagen, Denmark.
Treatment strategies focus on inhibition of interleukin (IL)-23, which is an activator of TRM T cells and probably keeps them alive, according to Dr. Eidsmo. “The hope is that these cells can be silenced by IL-23 inhibition, which is a great idea, and it probably works. It’s just a matter of what is the readout of long-term remission, because the big challenge in the clinical world is when do we stop these expensive biological treatments? When can we feel secure that patients are in deep remission?” she asked.
TRM cells are also far from the only immune cells involved in psoriasis. Others include keratinocytes, Langerhans cells, and fibroblasts. Dr. Eidsmo referenced a recent spatial analysis that used single-cell and spatial RNA sequencing to identify the localization of specific cell populations and inflammatory pathways within psoriasis lesions and epidermal compartments as well as also suggested crosstalk links between cell types. Epigenetic changes in stem cells may also maintain a lower threshold for tissue inflammation.
Dr. Eidsmo advised caution in eliminating TRM T cells, which play a key role in protecting against melanoma and other cancers, especially later in life. “We don’t want to get rid of them. We want to have the right balance.”
She noted a study in her own lab that mapped TRM T cells in healthy epidermis and found that they could be renewed from both circulating precursors and cells within the epidermis. “So getting rid of the mature TRM T cells will most likely just lead to a new generation of the same subset.”
Other data show that there are a wide range of subsets of TRM T cells, and she recommended focusing on the functionality of TRM T cells rather than sheer numbers. “This is something we’re working on now: Can we change the functionality [of TRM T cells], rather than eradicate them and hope for the best in the next generation? Can we change the functionality of the T cells we already have in the skin?”
There is also epigenetic data in TRM T cells, keratinocytes, stem cells, and other cells thus suggesting complexity and plasticity in the system that remains poorly understood.
Taken together, the research is at too early of a stage to be clinically useful, said Dr. Eidsmo. “We need to go back to the drawing board and just realize what we need to measure, and with the new techniques coming out, maybe spatial [measurement] at a high resolution, we can find biomarkers that better dictate the future of this. Be a little bit wary when you read the outcomes from the clinical trials that are ongoing, because right now, it’s a bit of a race between different biologics. These cells are used as a readout of efficacy of the treatments, and we’re not quite there yet.”
During the Q&A session after the presentation, one audience member asked about the heterogeneity of cells found within the skin of patients with psoriasis and pointed out that many proinflammatory cells likely play a role in tumor control. Dr. Eidsmo responded that her group’s analysis of a large database of patients with metastatic melanoma found that a factor that is important to the development of TRM T cells was strongly correlated to survival in patients with metastatic melanoma receiving immune checkpoint blockade. “So we really don’t want to eradicate them,” she said.
Also during the Q&A, Iain McInnes, MD, PhD, commented about the need to understand the previous events that drove the creation of memory T cells. “For me, the question is about the hierarchy, the primacy of what really drives the memory. In the infectious world, we’re trained to think [that memory responses] are T cell driven memory, but I wonder whether you have an idea of whether the T cell is responding to other memories, particularly in the stroma. Because certainly in the arthropathies, we have really good evidence now of epigenetic change in the synovial stroma and subsets,” said Dr. McInnes, who is director of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow, Glasgow, Scotland.
Dr. Eidsmo responded that she believes responses are different among different individuals. “We know too little about how these two systems interact with one another. I think the TRM T cells are very good at amplifying the stroma to recruit cells in. I think we need to think of two-step therapies. You need to normalize this [stromal] environment. How you can do that, I don’t know.”
Dr. McInnes agreed. “As a myeloid doctor, I strongly believe that perpetuators are innate and the adaptive is following on. But how do we test that? That’s really hard,” he said.
Dr. Eidsmo did not list any disclosures. Dr. McInnes has financial relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, Boehringer, Compugen, Cabaletta, Causeway, Dextera, Eli Lilly, Celgene, MoonLake, Pfizer, Novartis, Janssen, Roche, Versus Arthritis, MRC, and UCB.
SEATTLE — In fact, flare-ups often recur at the same site, a phenomenon that might be driven by these resident memory cells, according to Liv Eidsmo, MD, PhD.
This has led to their use as biomarkers in clinical trials for new therapies, but TRM T cells have a complex biology that is far from fully understood, Dr. Eidsmo said at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. “With time, we’re understanding that the regulation of the functionality is more complicated than we thought, so following these cells as a positive outcome of a clinical trial is a little bit premature,” said Dr. Eidsmo, who is a consultant dermatologist at the University of Copenhagen, Copenhagen, Denmark.
Treatment strategies focus on inhibition of interleukin (IL)-23, which is an activator of TRM T cells and probably keeps them alive, according to Dr. Eidsmo. “The hope is that these cells can be silenced by IL-23 inhibition, which is a great idea, and it probably works. It’s just a matter of what is the readout of long-term remission, because the big challenge in the clinical world is when do we stop these expensive biological treatments? When can we feel secure that patients are in deep remission?” she asked.
TRM cells are also far from the only immune cells involved in psoriasis. Others include keratinocytes, Langerhans cells, and fibroblasts. Dr. Eidsmo referenced a recent spatial analysis that used single-cell and spatial RNA sequencing to identify the localization of specific cell populations and inflammatory pathways within psoriasis lesions and epidermal compartments as well as also suggested crosstalk links between cell types. Epigenetic changes in stem cells may also maintain a lower threshold for tissue inflammation.
Dr. Eidsmo advised caution in eliminating TRM T cells, which play a key role in protecting against melanoma and other cancers, especially later in life. “We don’t want to get rid of them. We want to have the right balance.”
She noted a study in her own lab that mapped TRM T cells in healthy epidermis and found that they could be renewed from both circulating precursors and cells within the epidermis. “So getting rid of the mature TRM T cells will most likely just lead to a new generation of the same subset.”
Other data show that there are a wide range of subsets of TRM T cells, and she recommended focusing on the functionality of TRM T cells rather than sheer numbers. “This is something we’re working on now: Can we change the functionality [of TRM T cells], rather than eradicate them and hope for the best in the next generation? Can we change the functionality of the T cells we already have in the skin?”
There is also epigenetic data in TRM T cells, keratinocytes, stem cells, and other cells thus suggesting complexity and plasticity in the system that remains poorly understood.
Taken together, the research is at too early of a stage to be clinically useful, said Dr. Eidsmo. “We need to go back to the drawing board and just realize what we need to measure, and with the new techniques coming out, maybe spatial [measurement] at a high resolution, we can find biomarkers that better dictate the future of this. Be a little bit wary when you read the outcomes from the clinical trials that are ongoing, because right now, it’s a bit of a race between different biologics. These cells are used as a readout of efficacy of the treatments, and we’re not quite there yet.”
During the Q&A session after the presentation, one audience member asked about the heterogeneity of cells found within the skin of patients with psoriasis and pointed out that many proinflammatory cells likely play a role in tumor control. Dr. Eidsmo responded that her group’s analysis of a large database of patients with metastatic melanoma found that a factor that is important to the development of TRM T cells was strongly correlated to survival in patients with metastatic melanoma receiving immune checkpoint blockade. “So we really don’t want to eradicate them,” she said.
Also during the Q&A, Iain McInnes, MD, PhD, commented about the need to understand the previous events that drove the creation of memory T cells. “For me, the question is about the hierarchy, the primacy of what really drives the memory. In the infectious world, we’re trained to think [that memory responses] are T cell driven memory, but I wonder whether you have an idea of whether the T cell is responding to other memories, particularly in the stroma. Because certainly in the arthropathies, we have really good evidence now of epigenetic change in the synovial stroma and subsets,” said Dr. McInnes, who is director of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow, Glasgow, Scotland.
Dr. Eidsmo responded that she believes responses are different among different individuals. “We know too little about how these two systems interact with one another. I think the TRM T cells are very good at amplifying the stroma to recruit cells in. I think we need to think of two-step therapies. You need to normalize this [stromal] environment. How you can do that, I don’t know.”
Dr. McInnes agreed. “As a myeloid doctor, I strongly believe that perpetuators are innate and the adaptive is following on. But how do we test that? That’s really hard,” he said.
Dr. Eidsmo did not list any disclosures. Dr. McInnes has financial relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, Boehringer, Compugen, Cabaletta, Causeway, Dextera, Eli Lilly, Celgene, MoonLake, Pfizer, Novartis, Janssen, Roche, Versus Arthritis, MRC, and UCB.
SEATTLE — In fact, flare-ups often recur at the same site, a phenomenon that might be driven by these resident memory cells, according to Liv Eidsmo, MD, PhD.
This has led to their use as biomarkers in clinical trials for new therapies, but TRM T cells have a complex biology that is far from fully understood, Dr. Eidsmo said at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. “With time, we’re understanding that the regulation of the functionality is more complicated than we thought, so following these cells as a positive outcome of a clinical trial is a little bit premature,” said Dr. Eidsmo, who is a consultant dermatologist at the University of Copenhagen, Copenhagen, Denmark.
Treatment strategies focus on inhibition of interleukin (IL)-23, which is an activator of TRM T cells and probably keeps them alive, according to Dr. Eidsmo. “The hope is that these cells can be silenced by IL-23 inhibition, which is a great idea, and it probably works. It’s just a matter of what is the readout of long-term remission, because the big challenge in the clinical world is when do we stop these expensive biological treatments? When can we feel secure that patients are in deep remission?” she asked.
TRM cells are also far from the only immune cells involved in psoriasis. Others include keratinocytes, Langerhans cells, and fibroblasts. Dr. Eidsmo referenced a recent spatial analysis that used single-cell and spatial RNA sequencing to identify the localization of specific cell populations and inflammatory pathways within psoriasis lesions and epidermal compartments as well as also suggested crosstalk links between cell types. Epigenetic changes in stem cells may also maintain a lower threshold for tissue inflammation.
Dr. Eidsmo advised caution in eliminating TRM T cells, which play a key role in protecting against melanoma and other cancers, especially later in life. “We don’t want to get rid of them. We want to have the right balance.”
She noted a study in her own lab that mapped TRM T cells in healthy epidermis and found that they could be renewed from both circulating precursors and cells within the epidermis. “So getting rid of the mature TRM T cells will most likely just lead to a new generation of the same subset.”
Other data show that there are a wide range of subsets of TRM T cells, and she recommended focusing on the functionality of TRM T cells rather than sheer numbers. “This is something we’re working on now: Can we change the functionality [of TRM T cells], rather than eradicate them and hope for the best in the next generation? Can we change the functionality of the T cells we already have in the skin?”
There is also epigenetic data in TRM T cells, keratinocytes, stem cells, and other cells thus suggesting complexity and plasticity in the system that remains poorly understood.
Taken together, the research is at too early of a stage to be clinically useful, said Dr. Eidsmo. “We need to go back to the drawing board and just realize what we need to measure, and with the new techniques coming out, maybe spatial [measurement] at a high resolution, we can find biomarkers that better dictate the future of this. Be a little bit wary when you read the outcomes from the clinical trials that are ongoing, because right now, it’s a bit of a race between different biologics. These cells are used as a readout of efficacy of the treatments, and we’re not quite there yet.”
During the Q&A session after the presentation, one audience member asked about the heterogeneity of cells found within the skin of patients with psoriasis and pointed out that many proinflammatory cells likely play a role in tumor control. Dr. Eidsmo responded that her group’s analysis of a large database of patients with metastatic melanoma found that a factor that is important to the development of TRM T cells was strongly correlated to survival in patients with metastatic melanoma receiving immune checkpoint blockade. “So we really don’t want to eradicate them,” she said.
Also during the Q&A, Iain McInnes, MD, PhD, commented about the need to understand the previous events that drove the creation of memory T cells. “For me, the question is about the hierarchy, the primacy of what really drives the memory. In the infectious world, we’re trained to think [that memory responses] are T cell driven memory, but I wonder whether you have an idea of whether the T cell is responding to other memories, particularly in the stroma. Because certainly in the arthropathies, we have really good evidence now of epigenetic change in the synovial stroma and subsets,” said Dr. McInnes, who is director of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow, Glasgow, Scotland.
Dr. Eidsmo responded that she believes responses are different among different individuals. “We know too little about how these two systems interact with one another. I think the TRM T cells are very good at amplifying the stroma to recruit cells in. I think we need to think of two-step therapies. You need to normalize this [stromal] environment. How you can do that, I don’t know.”
Dr. McInnes agreed. “As a myeloid doctor, I strongly believe that perpetuators are innate and the adaptive is following on. But how do we test that? That’s really hard,” he said.
Dr. Eidsmo did not list any disclosures. Dr. McInnes has financial relationships with AbbVie, AstraZeneca, Bristol-Myers Squibb, Boehringer, Compugen, Cabaletta, Causeway, Dextera, Eli Lilly, Celgene, MoonLake, Pfizer, Novartis, Janssen, Roche, Versus Arthritis, MRC, and UCB.
FROM GRAPPA 2024
Study Identifies Plasma Proteins Linked to Increased PsA Risk
Key clinical point: Levels of certain proteins found in the blood plasma affected the risk for development of psoriatic arthritis (PsA) and could serve as potential therapeutic targets for the condition.
Major finding: Apolipoprotein F increased the risk for PsA by 60% (odds ratio [OR] 1.69; PFDR < .001), whereas interleukin-10 reduced the risk for PsA by 40% (OR 0.60; PFDR = .034). Other proteins associated with an increased risk for PsA included tumor necrosis factor, V-type proton ATPase subunit G 2, receptor-type tyrosine protein phosphatase F, and septin-8.
Study details: This two-sample Mendelian randomization analysis included the data of 3537 patients with PsA and 262,844 control individuals without PsA from the FinnGen study and the data of 1837 unique plasma proteins from a genome-wide association study within the UK Biobank Pharma Proteomics Project.
Disclosures: This study was supported by the Natural Science Foundation of Guangxi Province and the National Natural Science Foundation of China. The authors declared no conflicts of interest.
Source: Zhao H, Zhou Y, Wang Z, Zhang X, Chen L, Hong Z. Plasma proteins and psoriatic arthritis: A proteome-wide Mendelian randomization study. Front Immunol. 15:1417564 (July 3). Doi: 10.3389/fimmu.2024.1417564 Source
Key clinical point: Levels of certain proteins found in the blood plasma affected the risk for development of psoriatic arthritis (PsA) and could serve as potential therapeutic targets for the condition.
Major finding: Apolipoprotein F increased the risk for PsA by 60% (odds ratio [OR] 1.69; PFDR < .001), whereas interleukin-10 reduced the risk for PsA by 40% (OR 0.60; PFDR = .034). Other proteins associated with an increased risk for PsA included tumor necrosis factor, V-type proton ATPase subunit G 2, receptor-type tyrosine protein phosphatase F, and septin-8.
Study details: This two-sample Mendelian randomization analysis included the data of 3537 patients with PsA and 262,844 control individuals without PsA from the FinnGen study and the data of 1837 unique plasma proteins from a genome-wide association study within the UK Biobank Pharma Proteomics Project.
Disclosures: This study was supported by the Natural Science Foundation of Guangxi Province and the National Natural Science Foundation of China. The authors declared no conflicts of interest.
Source: Zhao H, Zhou Y, Wang Z, Zhang X, Chen L, Hong Z. Plasma proteins and psoriatic arthritis: A proteome-wide Mendelian randomization study. Front Immunol. 15:1417564 (July 3). Doi: 10.3389/fimmu.2024.1417564 Source
Key clinical point: Levels of certain proteins found in the blood plasma affected the risk for development of psoriatic arthritis (PsA) and could serve as potential therapeutic targets for the condition.
Major finding: Apolipoprotein F increased the risk for PsA by 60% (odds ratio [OR] 1.69; PFDR < .001), whereas interleukin-10 reduced the risk for PsA by 40% (OR 0.60; PFDR = .034). Other proteins associated with an increased risk for PsA included tumor necrosis factor, V-type proton ATPase subunit G 2, receptor-type tyrosine protein phosphatase F, and septin-8.
Study details: This two-sample Mendelian randomization analysis included the data of 3537 patients with PsA and 262,844 control individuals without PsA from the FinnGen study and the data of 1837 unique plasma proteins from a genome-wide association study within the UK Biobank Pharma Proteomics Project.
Disclosures: This study was supported by the Natural Science Foundation of Guangxi Province and the National Natural Science Foundation of China. The authors declared no conflicts of interest.
Source: Zhao H, Zhou Y, Wang Z, Zhang X, Chen L, Hong Z. Plasma proteins and psoriatic arthritis: A proteome-wide Mendelian randomization study. Front Immunol. 15:1417564 (July 3). Doi: 10.3389/fimmu.2024.1417564 Source
Impact of Smoking and Diabetes on PsA Risk in Psoriasis Patients
Key clinical point: The presence of type 2 diabetes (T2D) and smoking history increased the risk for psoriatic arthritis (PsA) in patients with psoriasis; however, T2D seemed to have a greater impact than smoking history in increasing incidence rate of PsA.
Major finding: The risk for PsA was significantly higher in patients with psoriasis who did vs did not have T2D (hazard ratio [HR] 1.11; 95% CI 1.03-1.20) and in those with vs without smoking history (HR 1.11; 95% CI 1.06-1.17). However, the risk was not significant in patients with psoriasis and T2D with vs without smoking history (HR 1.05; 95% CI 0.92-1.20).
Study details: This retrospective cohort study included patients with psoriasis with or without T2D (n = 42,315 each), those with or without smoking history (n = 74,046 each), and those with T2D with or without smoking history (n = 13,065 each).
Disclosures: This study was funded by the Chung Shan Medical University Hospital research project. The authors declared no conflicts of interest.
Source: Huo A-P, Liao P-L, Leong P-Y, Wei JC-C. From psoriasis to psoriatic arthritis: Epidemiological insights from a retrospective cohort study of 74,046 patients. Front Med. 2024;11:1419722 (June 26). Doi: 10.3389/fmed.2024.1419722 Source
Key clinical point: The presence of type 2 diabetes (T2D) and smoking history increased the risk for psoriatic arthritis (PsA) in patients with psoriasis; however, T2D seemed to have a greater impact than smoking history in increasing incidence rate of PsA.
Major finding: The risk for PsA was significantly higher in patients with psoriasis who did vs did not have T2D (hazard ratio [HR] 1.11; 95% CI 1.03-1.20) and in those with vs without smoking history (HR 1.11; 95% CI 1.06-1.17). However, the risk was not significant in patients with psoriasis and T2D with vs without smoking history (HR 1.05; 95% CI 0.92-1.20).
Study details: This retrospective cohort study included patients with psoriasis with or without T2D (n = 42,315 each), those with or without smoking history (n = 74,046 each), and those with T2D with or without smoking history (n = 13,065 each).
Disclosures: This study was funded by the Chung Shan Medical University Hospital research project. The authors declared no conflicts of interest.
Source: Huo A-P, Liao P-L, Leong P-Y, Wei JC-C. From psoriasis to psoriatic arthritis: Epidemiological insights from a retrospective cohort study of 74,046 patients. Front Med. 2024;11:1419722 (June 26). Doi: 10.3389/fmed.2024.1419722 Source
Key clinical point: The presence of type 2 diabetes (T2D) and smoking history increased the risk for psoriatic arthritis (PsA) in patients with psoriasis; however, T2D seemed to have a greater impact than smoking history in increasing incidence rate of PsA.
Major finding: The risk for PsA was significantly higher in patients with psoriasis who did vs did not have T2D (hazard ratio [HR] 1.11; 95% CI 1.03-1.20) and in those with vs without smoking history (HR 1.11; 95% CI 1.06-1.17). However, the risk was not significant in patients with psoriasis and T2D with vs without smoking history (HR 1.05; 95% CI 0.92-1.20).
Study details: This retrospective cohort study included patients with psoriasis with or without T2D (n = 42,315 each), those with or without smoking history (n = 74,046 each), and those with T2D with or without smoking history (n = 13,065 each).
Disclosures: This study was funded by the Chung Shan Medical University Hospital research project. The authors declared no conflicts of interest.
Source: Huo A-P, Liao P-L, Leong P-Y, Wei JC-C. From psoriasis to psoriatic arthritis: Epidemiological insights from a retrospective cohort study of 74,046 patients. Front Med. 2024;11:1419722 (June 26). Doi: 10.3389/fmed.2024.1419722 Source
Periodontitis Impacts Oral Health-Related Quality of Life in PsA
Key clinical point: In individuals with vs without psoriatic arthritis (PsA), periodontitis was highly prevalent and negatively affected oral Health-Related Quality of Life (HRQOL).
Major finding: Individuals with vs without PsA were 2.67 times more likely to develop periodontitis (prevalence 57.0% vs 33.1%; odds ratio 2.67; P < .001), which was significantly associated with worsened oral HRQOL (odds ratio 1.92; P < .001). The mean Oral Impacts on Daily Performance scores, indicative of oral HRQOL, were also higher in individuals with vs without PsA (P < .001).
Study details: This case-control study included 86 individuals with PsA, 210 individuals with psoriasis, and 359 control individuals without psoriasis, all age 35-65 years and having ≥ 14 teeth.
Disclosures: This study was supported by the National Council for Scientific and Technological Development - CNPq, Brazil. The authors declared no conflicts of interest.
Source: Costa AA, Cota LOM, Esteves Lima RP, et al. The association between periodontitis and the impact of oral health on the quality of life of individuals with psoriasis and psoriatic arthritis. PLoS One. 2024;19(6):e0301158 (June 25). Doi: 10.1371/journal.pone.0301158 Source
Key clinical point: In individuals with vs without psoriatic arthritis (PsA), periodontitis was highly prevalent and negatively affected oral Health-Related Quality of Life (HRQOL).
Major finding: Individuals with vs without PsA were 2.67 times more likely to develop periodontitis (prevalence 57.0% vs 33.1%; odds ratio 2.67; P < .001), which was significantly associated with worsened oral HRQOL (odds ratio 1.92; P < .001). The mean Oral Impacts on Daily Performance scores, indicative of oral HRQOL, were also higher in individuals with vs without PsA (P < .001).
Study details: This case-control study included 86 individuals with PsA, 210 individuals with psoriasis, and 359 control individuals without psoriasis, all age 35-65 years and having ≥ 14 teeth.
Disclosures: This study was supported by the National Council for Scientific and Technological Development - CNPq, Brazil. The authors declared no conflicts of interest.
Source: Costa AA, Cota LOM, Esteves Lima RP, et al. The association between periodontitis and the impact of oral health on the quality of life of individuals with psoriasis and psoriatic arthritis. PLoS One. 2024;19(6):e0301158 (June 25). Doi: 10.1371/journal.pone.0301158 Source
Key clinical point: In individuals with vs without psoriatic arthritis (PsA), periodontitis was highly prevalent and negatively affected oral Health-Related Quality of Life (HRQOL).
Major finding: Individuals with vs without PsA were 2.67 times more likely to develop periodontitis (prevalence 57.0% vs 33.1%; odds ratio 2.67; P < .001), which was significantly associated with worsened oral HRQOL (odds ratio 1.92; P < .001). The mean Oral Impacts on Daily Performance scores, indicative of oral HRQOL, were also higher in individuals with vs without PsA (P < .001).
Study details: This case-control study included 86 individuals with PsA, 210 individuals with psoriasis, and 359 control individuals without psoriasis, all age 35-65 years and having ≥ 14 teeth.
Disclosures: This study was supported by the National Council for Scientific and Technological Development - CNPq, Brazil. The authors declared no conflicts of interest.
Source: Costa AA, Cota LOM, Esteves Lima RP, et al. The association between periodontitis and the impact of oral health on the quality of life of individuals with psoriasis and psoriatic arthritis. PLoS One. 2024;19(6):e0301158 (June 25). Doi: 10.1371/journal.pone.0301158 Source
Sedentary Lifestyle Linked to Increased Disease Burden in PsA
Key clinical point: Around 25% patients with psoriatic arthritis (PsA) had a sedentary lifestyle (< 90 min of physical activity per week), with lack of physical activity associated with pain, worsened clinical activity, functionality, and disease impact.
Major finding: Overall, 25.9% of patients had a sedentary lifestyle. Patients with a sedentary vs non-sedentary lifestyle had more enthesitis, fatigue, higher disease activity, greater disease impact, and lower functionality (all P < .05). Sedentary lifestyle was also associated with increased risk for pain (odds ratio 1.5; P < .001).
Study details: This cross-sectional study included 232 patients with PsA aged 18-69 years with no radiographic damage or respiratory or cardiac diseases that limit physical activity.
Disclosures: This study did not receive any financial support. The authors declared no conflicts of interest. During the review, the reviewer declared a shared affiliation, with no collaboration, of the lead author to the handling editor.
Source: Toledano E, Chacón CC, Compán O, et al. Analysis of physical activity in psoriatic arthritis: Relationship with clinical and analytical parameters and comorbidity—description of the sedentary patient. Front Med. 2024;11:1385842 (June 23). Doi: 10.3389/fmed.2024.1385842 Source
Key clinical point: Around 25% patients with psoriatic arthritis (PsA) had a sedentary lifestyle (< 90 min of physical activity per week), with lack of physical activity associated with pain, worsened clinical activity, functionality, and disease impact.
Major finding: Overall, 25.9% of patients had a sedentary lifestyle. Patients with a sedentary vs non-sedentary lifestyle had more enthesitis, fatigue, higher disease activity, greater disease impact, and lower functionality (all P < .05). Sedentary lifestyle was also associated with increased risk for pain (odds ratio 1.5; P < .001).
Study details: This cross-sectional study included 232 patients with PsA aged 18-69 years with no radiographic damage or respiratory or cardiac diseases that limit physical activity.
Disclosures: This study did not receive any financial support. The authors declared no conflicts of interest. During the review, the reviewer declared a shared affiliation, with no collaboration, of the lead author to the handling editor.
Source: Toledano E, Chacón CC, Compán O, et al. Analysis of physical activity in psoriatic arthritis: Relationship with clinical and analytical parameters and comorbidity—description of the sedentary patient. Front Med. 2024;11:1385842 (June 23). Doi: 10.3389/fmed.2024.1385842 Source
Key clinical point: Around 25% patients with psoriatic arthritis (PsA) had a sedentary lifestyle (< 90 min of physical activity per week), with lack of physical activity associated with pain, worsened clinical activity, functionality, and disease impact.
Major finding: Overall, 25.9% of patients had a sedentary lifestyle. Patients with a sedentary vs non-sedentary lifestyle had more enthesitis, fatigue, higher disease activity, greater disease impact, and lower functionality (all P < .05). Sedentary lifestyle was also associated with increased risk for pain (odds ratio 1.5; P < .001).
Study details: This cross-sectional study included 232 patients with PsA aged 18-69 years with no radiographic damage or respiratory or cardiac diseases that limit physical activity.
Disclosures: This study did not receive any financial support. The authors declared no conflicts of interest. During the review, the reviewer declared a shared affiliation, with no collaboration, of the lead author to the handling editor.
Source: Toledano E, Chacón CC, Compán O, et al. Analysis of physical activity in psoriatic arthritis: Relationship with clinical and analytical parameters and comorbidity—description of the sedentary patient. Front Med. 2024;11:1385842 (June 23). Doi: 10.3389/fmed.2024.1385842 Source
Genetically Mimicked IL-13 Inhibition Raises PsA Risk
Key clinical point: A genetic variant of the IL-13 gene that was designed to mimic the therapeutic effects of interleukin-13 (IL-13) inhibition was associated with an increased risk for psoriatic arthritis (PsA).
Major finding: IL-13 inhibition, genetically mimicked using an IL-13 gene variant was associated with an increased risk for PsA (odds ratio 37.39; P = 1.64×10-9).
Study details: This two-sample Mendelian randomization study analyzed the data of 563,946 individuals with exposure to IL-13 inhibition while the genetic outcomes were assessed in 3609 patients with PsA and 9192 control individuals without PsA.
Disclosures: This study was supported by the National Institute for Health Research Manchester Biomedical Research Centre, UK. Three authors declared receiving grants, consulting fees, speaker fees, honoraria, or travel support from various sources unrelated to this study. Other authors declared no conflicts of interest.
Source: Zhao SS, Hyrich K, Yiu Z, et al. Genetically proxied IL-13 inhibition is associated with risk of psoriatic disease: Mendelian randomization study. Arthritis Rheumatol. 2024 (July 8). Doi: 10.1002/art.42942 Source
Key clinical point: A genetic variant of the IL-13 gene that was designed to mimic the therapeutic effects of interleukin-13 (IL-13) inhibition was associated with an increased risk for psoriatic arthritis (PsA).
Major finding: IL-13 inhibition, genetically mimicked using an IL-13 gene variant was associated with an increased risk for PsA (odds ratio 37.39; P = 1.64×10-9).
Study details: This two-sample Mendelian randomization study analyzed the data of 563,946 individuals with exposure to IL-13 inhibition while the genetic outcomes were assessed in 3609 patients with PsA and 9192 control individuals without PsA.
Disclosures: This study was supported by the National Institute for Health Research Manchester Biomedical Research Centre, UK. Three authors declared receiving grants, consulting fees, speaker fees, honoraria, or travel support from various sources unrelated to this study. Other authors declared no conflicts of interest.
Source: Zhao SS, Hyrich K, Yiu Z, et al. Genetically proxied IL-13 inhibition is associated with risk of psoriatic disease: Mendelian randomization study. Arthritis Rheumatol. 2024 (July 8). Doi: 10.1002/art.42942 Source
Key clinical point: A genetic variant of the IL-13 gene that was designed to mimic the therapeutic effects of interleukin-13 (IL-13) inhibition was associated with an increased risk for psoriatic arthritis (PsA).
Major finding: IL-13 inhibition, genetically mimicked using an IL-13 gene variant was associated with an increased risk for PsA (odds ratio 37.39; P = 1.64×10-9).
Study details: This two-sample Mendelian randomization study analyzed the data of 563,946 individuals with exposure to IL-13 inhibition while the genetic outcomes were assessed in 3609 patients with PsA and 9192 control individuals without PsA.
Disclosures: This study was supported by the National Institute for Health Research Manchester Biomedical Research Centre, UK. Three authors declared receiving grants, consulting fees, speaker fees, honoraria, or travel support from various sources unrelated to this study. Other authors declared no conflicts of interest.
Source: Zhao SS, Hyrich K, Yiu Z, et al. Genetically proxied IL-13 inhibition is associated with risk of psoriatic disease: Mendelian randomization study. Arthritis Rheumatol. 2024 (July 8). Doi: 10.1002/art.42942 Source
Multimorbidity Worsens Quality of Life in Patients With PsA
Key clinical point: Multimorbidity was present in nearly 50% of patients with psoriatic arthritis (PsA) and significantly affected the physical aspects of their quality of life.
Major finding: Multimorbidity was observed in 50.2% patients, with cardiovascular diseases being the most prevalent comorbidity. Patients with vs without multimorbidity had worsened scores for various 36-Item Short Form Health Survey domains, including bodily pain (34.7 vs 47.5; P < .01), physical functioning (52.1 vs 63.1; P < .01), and ability to perform roles due to physical health problems (28.5 vs 42.8; P < .01).
Study details: This cross-sectional observational study included 267 patients with PsA, age > 18 years.
Disclosures: This study was supported by a grant from the National Centre for Research and Development, Warsaw, Poland. The authors declared no conflicts of interest.
Source: Biedroń G, Wilk M, Nowakowski J, et al. Impact of comorbidities on patient-reported outcomes in psoriatic arthritis: A single centre cohort study. Rheumatol Int. Published online 2024;44:1435-1443. Doi: 10.1007/s00296-024-05632-2 Source
Key clinical point: Multimorbidity was present in nearly 50% of patients with psoriatic arthritis (PsA) and significantly affected the physical aspects of their quality of life.
Major finding: Multimorbidity was observed in 50.2% patients, with cardiovascular diseases being the most prevalent comorbidity. Patients with vs without multimorbidity had worsened scores for various 36-Item Short Form Health Survey domains, including bodily pain (34.7 vs 47.5; P < .01), physical functioning (52.1 vs 63.1; P < .01), and ability to perform roles due to physical health problems (28.5 vs 42.8; P < .01).
Study details: This cross-sectional observational study included 267 patients with PsA, age > 18 years.
Disclosures: This study was supported by a grant from the National Centre for Research and Development, Warsaw, Poland. The authors declared no conflicts of interest.
Source: Biedroń G, Wilk M, Nowakowski J, et al. Impact of comorbidities on patient-reported outcomes in psoriatic arthritis: A single centre cohort study. Rheumatol Int. Published online 2024;44:1435-1443. Doi: 10.1007/s00296-024-05632-2 Source
Key clinical point: Multimorbidity was present in nearly 50% of patients with psoriatic arthritis (PsA) and significantly affected the physical aspects of their quality of life.
Major finding: Multimorbidity was observed in 50.2% patients, with cardiovascular diseases being the most prevalent comorbidity. Patients with vs without multimorbidity had worsened scores for various 36-Item Short Form Health Survey domains, including bodily pain (34.7 vs 47.5; P < .01), physical functioning (52.1 vs 63.1; P < .01), and ability to perform roles due to physical health problems (28.5 vs 42.8; P < .01).
Study details: This cross-sectional observational study included 267 patients with PsA, age > 18 years.
Disclosures: This study was supported by a grant from the National Centre for Research and Development, Warsaw, Poland. The authors declared no conflicts of interest.
Source: Biedroń G, Wilk M, Nowakowski J, et al. Impact of comorbidities on patient-reported outcomes in psoriatic arthritis: A single centre cohort study. Rheumatol Int. Published online 2024;44:1435-1443. Doi: 10.1007/s00296-024-05632-2 Source