Robert Spiera

Objectives: To evaluate contemporary global treatment of diffuse cutaneous systemic sclerosis (dcSSc) skin by SSc specialists. Methods: An anonymous survey was distributed via the Scleroderma Clinical Trials Consortium, European Scleroderma Trials and Research Group (EUSTAR), and Collaborative National Quality and Efficacy Registry (CONQUER) distribution lists between June–September 2025. The survey comprised four sections: Demographics, Treatment of dcSSc Skin, Impact of Recent Guidelines, and Clinical Trials. Results: Responses included 103 physicians (93 completed): 43% North America, 31% Europe, 15% South America, and 12% elsewhere. The majority practice within an SSc centre (80%) and participate in clinical trials (84%). Mycophenolate mofetil (MMF) was preferred first-line treatment (71%) for dcSSc without ILD, rising to 92% for dcSSc with mild/non-progressive ILD. For active skin involvement despite MMF, trial referral was preferred as next step irrespective of ILD (59% without ILD and 58% with ILD). Treatment preferences have evolved, with 40% increasing MMF use and 47% decreasing methotrexate use, over previous 2–3 years. Biologic use has increased, with 56% and 37% reporting increasing rituximab and tocilizumab use, respectively. For dcSSc without ILD, 85% have prescribed rituximab, and 65% have prescribed tocilizumab. Biologic availability has impacted trial enrolment (73% agreement). Treatment decision-making for dcSSc skin involvement has been materially influenced by recent BSR and/or EULAR guidelines (43% agreement). Conclusion: MMF is preferred first-line for dcSSc. In absence of compelling scientific justification for combination or step-up immunomodulatory approaches, trial referral is currently the preferred next treatment option. Biologic use is increasing which impacts trial enrolment.

Polymyalgia rheumatica is a common inflammatory disease characterized by pain and stiffness in the shoulders and hips. Glucocorticoids are the first-line treatment, but relapses and glucocorticoid-related toxic effects are common, which underscores the need for effective alternatives. Secukinumab is a fully human monoclonal antibody that selectively inhibits interleukin-17A. We enrolled patients with recently relapsed polymyalgia rheumatica and randomly assigned them, in a 1:1:1 ratio, to receive secukinumab at a dose of 300 mg (SEC-300 group), secukinumab at a dose of 150 mg (SEC-150 group), or placebo for 52 weeks. Patients in all the groups also received prednisone on a tapering schedule for 24 weeks. The primary outcome was sustained remission at week 52, defined as remission (the absence of signs or symptoms attributable to polymyalgia rheumatica and no new diagnosis of giant-cell arteritis that warranted escape or rescue treatment) that was sustained from week 12 until week 52. The annual cumulative glucocorticoid dose was a secondary outcome. Safety was also assessed. A total of 381 patients underwent randomization, and 127 were assigned to each group. At 52 weeks, sustained remission was observed in 41.2% (95% confidence interval [CI], 32.8 to 49.7) of the patients in the SEC-300 group, in 40.6% (95% CI, 32.2 to 49.0) of those in the SEC-150 group, and in 20.4% (95% CI, 13.6 to 27.2) of those in the placebo group (P<0.001 for the comparison of each secukinumab dose with placebo). The mean adjusted annual cumulative glucocorticoid dose was 1603.7 mg in the SEC-300 group, 1683.2 mg in the SEC-150 group, and 2093.0 mg in the placebo group. Serious adverse events occurred in 13.5% of the patients in the SEC-300 group, in 15.9% in the SEC-150 group, and in 14.2% in the placebo group. Nasopharyngitis, hypersensitivity reactions, urinary tract infections, fungal infections, and back pain were more common in the secukinumab groups than in the placebo group. Among patients with relapsed polymyalgia rheumatica, treatment with secukinumab plus a 24-week glucocorticoid taper resulted in a higher percentage of patients with remission and in lower cumulative glucocorticoid doses than a glucocorticoid taper alone. (Funded by Novartis; REPLENISH ClinicalTrials.gov number, NCT05767034.).

Objectives: To determine whether rheumatologists and pulmonologists have distinct disciplinary approaches to the management of systemic autoimmune rheumatic disease (SARD)-interstitial lung disease (ILD). Methods: This was a cross-sectional survey study of United States rheumatologists and pulmonologists. Surveys were electronically distributed to physicians identified through professional societies and social media. Surveys contained case questions on SARD-ILD management for patients with mixed connective tissue disease, idiopathic inflammatory myopathy, rheumatoid arthritis, systemic sclerosis and Sjogren’s with varying ILD severity (asymptomatic, symptomatic, progressive). Respondents also answered questions on treatment decision-making, comfort with pharmacologic modalities and opinions about interdisciplinary co-management. We analyzed responses submitted 5–9/2024. We compared specialists’ responses via univariate logistic regression, Chi-squared or Fisher’s exact tests; we performed multivariable logistic regression of case questions controlling for practice setting, clinical experience and geographic region. Results: Analyses included 309 participants (rheumatologists = 184, pulmonologists = 125). Compared with pulmonologists, rheumatologists were less likely to treat asymptomatic and symptomatic ILD with corticosteroids for all SARD except asymptomatic systemic sclerosis (odds ratios [OR] 0.14–0.45), and to treat progressive ILD with antifibrotics (OR 0.26–0.30). Conversely, rheumatologists were more likely than pulmonologists to either add or modify immunomodulation/immunosuppression for all symptomatic and progressive SARD-ILD (OR 1.82–5.44). There were disciplinary differences in the relative importance of clinical variables to treatment approaches. Specialists reported ownership over different domains of treatment decision-making and healthcare maintenance. Conclusion: This national study suggests distinct disciplinary approaches to management of SARD-ILD, and highlights opportunities to leverage complementary expertise through a co-management paradigm.

Objective: To evaluate the relationship of skin fibroblast CD34 and α‐smooth muscle actin (α‐SMA) and immune cell infiltration with disease duration in diffuse cutaneous systemic sclerosis (dcSSc) and identify predictors of improvement. Methods: Skin biopsies and clinical data were analyzed from patients with dcSSc enrolled in lenabasum (n = 79), belimumab (n = 18), or nilotinib (n = 8) trials. CD34 and α‐SMA were scored semiquantitatively. Immune cells (CD20+, CD3+, and CD123+) were counted. Clinical and histologic features were compared between those with early (5‐point decrease in modified Rodnan skin score (mRSS) at 52 weeks. An Akaike's information criterion–optimal multiple logistic regression model for clinical improvement among 68 mycophenolate mofetil (MMF) users was developed. Fibroblast spatial organization was visualized using imaging mass cytometry (IMC) in a representative sample. Results: Despite similar baseline mRSS, early disease was associated with lower CD34, higher α‐SMA, increased B cells, and greater mRSS improvement compared with later SSc. IMC demonstrated regions of CD34+ fibroblasts in superficial dermis and α‐SMA+ fibroblasts in deeper, collagen‐dense regions. Among MMF users, high CD34 and α‐SMA predicted improvement in early SSc; however, high α‐SMA predicted lower odds of improvement in later SSc. The probability of improvement was lowest in early SSc with α‐SMA ^low /CD34 ^low immunophenotype and later SSc with α‐SMA ^high . In later SSc, B cells were higher in α‐SMA ^high versus α‐SMA ^low skin. Conclusion: Fibroblast immunophenotype varied by baseline disease duration and improved model performance for identifying those with improvement on MMF. Skin biopsies may be useful for refining prognosis and guiding patient management decisions. image

Objective: To compare the efficacy of abatacept to placebo for the treatment of relapsing, nonsevere granulomatosis with polyangiitis (GPA). Methods: In this multicenter trial, eligible patients with relapsing, nonsevere GPA were randomized to receive abatacept 125 mg subcutaneously once a week or placebo, both together with prednisone 30 mg/day (or equivalent), tapered and discontinued at week 12. Patients already taking methotrexate, azathioprine, mycophenolate, or leflunomide continued this medication at a stable dose. Patients achieving remission remained on their randomized assignment until relapse, early termination, or the common close date 12 months after enrollment of the last patient. Those who had a nonsevere relapse, had nonsevere worsening, or were not in remission by month 6 had the option to receive open‐label abatacept. The primary end point was the rate of treatment failure, defined as relapse, disease worsening, or failure to achieve a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) of 0 or 1 by six months. Results: Sixty‐five patients were randomized; 34 received abatacept and 31 received placebo. No statistical difference in the treatment failure rate was found between those who received abatacept and those who received placebo ( P = 0.853). Treatment with abatacept did not demonstrate any statistical difference from placebo in key secondary end points, including time to full remission (BVAS/WG = 0), duration of glucocorticoid‐free remission, relapse severity, prevention of damage, and patient‐reported quality‐of‐life outcomes. There was no difference in the frequency or severity of adverse events between treatment arms, including infection. Conclusion: In patients with relapsing, nonsevere GPA, abatacept did not reduce the risk of relapse, severe worsening, or failure to achieve remission.

Objective: To describe the frequency and outcomes associated with self-reported frailty in patients with vasculitis.Methods: VascStrong is a longitudinal study using the Vasculitis Patient-Powered Research Network, an internet-based cohort of patients with vasculitis. Data collected included patient global assessment (PtGA) and several domains of the Patient-Reported Outcomes Measurement Information System (PROMIS). Frailty was measured at baseline and 1-year follow-up using the FRAIL scale, a 5-domain self-reported measure. Patients were classified as nonfrail, prefrail, and frail based on 0, 1-2, or ≥ 3 criteria, respectively. At follow-up, patients reported the occurrence over the prior year of hospitalizations, infections, fractures, and disease flares. A multivariable logistic regression was performed to identify factors associated with frailty.Results: The baseline survey included 328 patients. Patients had a mean age of 59.5 years, were predominantly female (71.6%) and non-Hispanic White. Prevalence of prefrailty and frailty was 42.1% and 21.6%, respectively. The majority of patients with each form of vasculitis were classified as frail or prefrail. Prefrail and frail patients reported worse PROMIS scores at baseline and follow-up. Frailty was independently associated with female sex, higher PtGA scores, being overweight, and obesity, but not with age. At 1 year, 272 of 328 (82.9%) patients answered the follow-up survey. Transitions in frailty status were observed in 99 (36.4%) patients. Hospitalizations and flares were more frequent in frail patients.Conclusion: Self-reported frailty or prefrailty is common in the majority of patients with multiple forms of vasculitis, indicating there is a substantial subset of patients at risk for worse outcomes.

Objective: An unmet need exists for glucocorticoid‐sparing treatments for patients with polymyalgia rheumatica (PMR). The antibody‐drug conjugate ABBV‐154 comprises adalimumab conjugated to a glucocorticoid receptor modulator. We evaluated ABBV‐154 versus placebo in patients with glucocorticoid‐dependent PMR.Methods: In this phase 2, randomized, double‐blind, placebo‐controlled, dose‐ranging study, eligible patients had confirmed PMR, glucocorticoid response and two or more unequivocal PMR flares while tapering glucocorticoids and still on ≥5 mg daily prednisone equivalent. Randomized patients received subcutaneous placebo or ABBV‐154 40, 150, or 340 mg once every other week. The primary efficacy endpoint was time to flare. The sponsor voluntarily terminated the study early.Results: Overall, 181 patients were randomized (placebo, n = 50; ABBV‐154: 40 mg, n = 42; 150 mg, n = 45; 340 mg, n = 44), and 67.4% completed study drug at week 24. Time to flare was longer for patients receiving ABBV‐154 than those receiving placebo, with Kaplan‐Meier estimate of 24‐week flare‐free rate being lower for placebo. The hazard ratios of ABBV‐154 versus placebo were 0.49 (95% confidence interval [CI], 0.27–0.88), P = 0.017 for 40 mg; 0.44 (95% CI, 0.25–0.79), P = 0.006 for 150 mg; 0.20 (95% CI, 0.09–0.42), P < 0.001 for 340 mg. Incidences of treatment‐emergent adverse events were similar between groups, and the most common across ABBV‐154 cohorts was COVID‐19 (16.0%).Conclusion: Treatment effects were observed for ABBV‐154 cohorts compared with placebo for time to flare. ABBV‐154 was generally well tolerated. Due to early study termination, results should be interpreted with caution.

Objectives: The RESOLVE‐1 trial of lenabasum in diffuse cutaneous systemic sclerosis (dcSSc) allowed background immunosuppressive therapy (IST) at the discretion of individual investigators, and no significant differences were observed between treatment arms. This provides a powerful opportunity to compare the relative efficacy of different ISTs in a well‐defined large cohort of patients with dcSSc.Methods: Prespecified IST categories, efficacy end points, baseline disease characteristics likely to influence efficacy outcomes, the definition of interstitial lung disease, definitions of IST use, and categories of IST use by which efficacy outcomes were evaluated were. Descriptive statistics are used to present results.Results: For skin, change in modified Rodnan skin score (mRSS) was numerically greatest with mycophenolate mofetil (MMF) treatment in patients with the earliest disease, reaching −10.8 points in the MMF group versus −4.8 points in the no IST group in patients with a disease duration ≤2 years. Other ISTs had improvements intermediate between that seen in the MMF and no IST groups. Forced vital capacity (mL) was stable over 52 weeks in patients in the MMF group compared to an around 160‐mL decline over 52 weeks in no IST group. Differences in outcome were observed between antinuclear antibody subgroups, with greater difference in favor of MMF for skin and lungs being observed in anti–topoisomerase 1 autoantibody–positive patients. In contrast, anti–RNA polymerase III autoantibody–positive patients in both the no IST and MMF groups improved rapidly, with a decrease in mRSS.Conclusion: Taken together, our findings robustly support routine use of MMF in dcSSc and show benefit especially in early‐stage disease. Those patients with high‐risk antibodies for lung fibrosis might be especially suitable for MMF treatment.