Response to Upadacitinib in New-Onset Versus Relapsing Giant Cell Arteritis: Two-Year Outcomes from the SELECT-GCA Phase 3 Trial

Presenter: Anisha Dua

In the 2-year phase 3 SELECT-GCA trial, continuous upadacitinib 15 mg/day (UPA15) provided durable disease control and a favorable benefit-risk profile in patients with new-onset and relapsing giant cell arteritis (GCA). The continuation of UPA15 vs. switch to placebo (PBO) was evaluated in patients with new-onset or relapsing disease who had participated in the SELECT-GCA.

Of 103 patients entering the second treatment period (PBO: n=35, UPA15: n=68), 72.8% had new-onset disease. Compared with placebo, UPA15 reduced the risk of disease flare by ≥90% across both subgroups, maintained higher remission rates, and delayed time to first flare. Glucocorticoid-sparing benefits were substantial, with a median cumulative glucocorticoid dose of 0 mg from weeks 52-104 vs. 110 mg and 2297 mg in placebo-treated new-onset and relapsing patients, respectively. Serious adverse event rates were generally comparable between groups, no major adverse cardiovascular events occurred with UPA15, and no new clinically meaningful safety risks were identified.

Given limited sample size of the relapsing subgroup, the findings warrant a cautious interpretation.

In SELECT-GCA, continuous upadacitinib 15 mg cut was associated with a ≥90% reduction in flare risk versus switching to placebo. Median cumulative glucocorticoid exposure during Weeks 52–104 was 0 mg with continued upadacitinib versus 110 mg and 2297 mg in the placebo new-onset and relapsing subgroups, respectively. Herpes zoster and CPK elevation rates were higher with upadacitinib than placebo. Findings should be interpreted cautiously because of the small subgroup sizes

Secukinumab in Patients with Polymyalgia Rheumatica: Subgroup Analyses of Week 52 Results of a Phase 3, Multicentre, Randomised, Double-Blind, Placebo-Controlled Trial (REPLENISH)

Presenter: Frank Buttgereit.

In the phase 3 REPLENISH trial, secukinumab (SEC), an IL-17A inhibitor, demonstrated superior efficacy vs. placebo in patients with relapsing polymyalgia rheumatica (PMR) receiving a 24-week prednisone taper. A total of 381 patients were randomized 1:1:1 (SEC 300 mg, n=127; SEC 150 mg, n=127; placebo, n=127). The mean age of the study population was 70 years and 70.3% of them were women. Both SEC doses met the primary endpoint of sustained remission at week 52 and improved complete sustained remission rates compared with placebo across all demographic and disease subgroups. SEC also showed a significant glucocorticoid-sparing effect. Numerically greater responses were observed with SEC 300 mg in older (≥75 years), heavier (≥90 kg), and higher prednisone-dose (15 mg/day) subgroups. Safety was consistent with the established secukinumab profile, with no new safety signals.

These subgroup findings support further evaluation of secukinumab  as a new treatment option for relapsing PMR, with consistent efficacy regardless of baseline patient characteristics.

In REPLENISH, secukinumab 150/300 mg improved sustained and complete remission at week 52 vs. placebo, reduced glucocorticoid use, showed consistent efficacy across subgroups, and revealed no new safety signals, in patients with relapsing PMR.

Obinutuzumab Induces Rapid and Durable Resolution of Clinical Disease Activity Across Active Clinical SLEDAI-2K Organ Domains in Patients with Systemic Lupus Erythematosus

Presenter: Edward Vital.

In the Phase III ALLEGORY trial, obinutuzumab (OBI) plus standard therapy demonstrated superior efficacy vs. placebo in patients with active systemic lupus erythematosus (SLE). At Week 52, OBI achieved greater resolution of key disease manifestations, including arthritis (75.2% vs. 50.3%), proteinuria (72.2% vs. 26.1%), mucosal ulcers (82.2% vs. 63.6%), rash (52.2% vs. 36.2%), alopecia (56.1% vs. 34.2%), vasculitis (68.4% vs. 42.9%), and hematologic involvement (47.6% vs. 18.8%). Mean cSLEDAI-2K improvement was greater with OBI (-7.36 vs. -5.6), with separation from placebo evident by Week 8. Clinical SRI-4 response rates were 74.8% vs. 50.0% (adjusted difference 24.7%; 95% CI 14.26-35.17). Joint-50 responses at Week 52 were 80.5% vs. 66.1%, supporting broad and rapid organ-specific efficacy. A higher proportion of patients treated with OBI vs PBO achieved a CLASI-50 response at W20 (71.7% vs. 56.0% [adjusted difference 16.81%; 95% CI, −1.34-34.96]). The same was maintained over time. 

ALLEGORY demonstrated broad efficacy of OBI across multiple SLE domains. OBI plus standard therapy showed rapid improvement by Week 8, supporting treat-to-target and steroid-sparing approaches.

In Phase III ALLEGORY, OBI plus standard therapy showed superior and rapid efficacy vs. placebo across multiple SLE manifestations, with improvements evident by Week 8 and sustained through Week 52.

Class -Level and Drug -Level Persistence of IL-17Ai Versus IL-23 Inhibitors in Psoriatic Arthritis: Results from the PPD CorEvitas PsA/SpA Registry

Presenter: Philip Mease.

This observational registry study compared 12‑month persistence of IL‑17A inhibitors (IL‑17Ai) and IL‑23 inhibitors (IL‑23i) in adults with psoriatic arthritis (PsA) initiating these therapies as their first use. 

Majority of the IL-17Ai cohort (66.5%) was initiated on secukinumab, the remainder 33.5% of the population in this cohort was treated with ixekizumab. In the IL-23i cohort, guselkumab and risankizumab accounted for 59.7% and 40.3% of initiations, respectively. The IL-17Ai cohort was more treatment-experienced, with prior b/tsDMARD exposure in 60.5% vs. 48.9% of IL-23i-treated patients.

The persistence with IL-17Ai and IL-23i was comparable over 12 months (IL-17Ai: n=385; 56.2%, 95% CI, 50.7-62.3 vs. IL-23i: n=233, 57.4%, 95% CI, 48.7-67.6). Drug-level persistence was 48.9% (95% CI, 43.4-55.1) and 54.1% (95% CI, 45.5-64.3), respectively. Persistence did not differ significantly between groups at the class level (HR 1.06; 95% CI, 0.78-1.46) or drug level (HR 1.19; 95% CI, 0.88-1.60), indicating similar treatment durability for both biologic classes in routine clinical practice. Both IL-17i and IL-23i demonstrated comparable 12-month persistence in PsA, with consistent findings across both class-level and drug-level analyses.

In this real-world PsA study, IL‑17Ai and IL‑23i showed similar 12‑month persistence in PsA, with no significant differences at class or drug level despite higher prior biologic use in the IL‑17Ai cohort.

Clinical Outcomes at Week 52 in Male and Female Patients with PsA Treated With Deucravacitinib: A Pooled Analysis of Pivotal Phase 3 Studies

Presenter: Lihi Eder.

This post hoc pooled analysis of the phase 3 POETYK PsA-1 and PsA-2 trials assessed whether long-term efficacy of deucravacitinib (DEUC) would differ by sex in patients with PsA. Clinical outcomes through Week 52 were evaluated across multiple joint, skin, functional, and disease activity measures.

Among 648 patients receiving continuous DEUC through Week 52 (331 males, 317 females), sustained efficacy was observed across musculoskeletal, dermatologic, and patient-reported outcomes. Responses were comparable between males and females, including ACR20 (64.0% vs. 61.2%), MDA (39.3% vs. 36.0%), PASI75 (56.6% vs. 64.5%), and DAPSA remission/LDA (57.1% vs. 53.0%), indicating no clinically meaningful sex-based differences in treatment response.

DEUC demonstrated sustained efficacy through Week 52 across disease activity, musculoskeletal and skin outcomes, and patient-reported measures in patients with active PsA, with no meaningful sex-based differences in treatment response.

Deucravacitinib showed sustained Week 52 efficacy across joint, skin, disease activity, and patient-reported outcomes in PsA. Responses were numerically similarbetween males and females. As this was a post hoc analysis, the findings do not establish the absence of sex-based treatment differences.

One-Year and Three-Year Comparative Outcomes Among Patients with Psoriasis Treated with Bimekizumab Versus Secukinumab: A Propensity Score-Matched Real-World Study

Presenter: Maya Khasho.

This retrospective real-world study compared 1- and 3-year outcomes in adults with psoriasis treated with bimekizumab or secukinumab. Using propensity score-matched TriNetX cohorts, the analysis evaluated risks of psoriatic arthritis, candidiasis, and all-cause hospitalization to assess the comparative long-term safety and effectiveness of both therapies.

After propensity score matching (n=1,992/cohort), bimekizumab and secukinumab showed similar 1-year risks of PsA (5.17% vs. 5.85%; RR 0.883) and hospitalization (3.60% vs. 4.65%; RR 0.773), but bimekizumab had higher candidiasis risk (5.52% vs. 2.10%; RR 2.631). At 3 years, bimekizumab was associated with lower risks of PsA (6.40% vs. 10.96%; RR 0.584) and hospitalization (3.90% vs. 9.31%; RR 0.418), while candidiasis remained higher (5.87% vs. 4.25%; RR 1.380).

The study identified associations with different recorded outcomes over 1 and 3 years. Given the retrospective observational design, residual confounding and differential follow-up limit conclusions regarding comparative safety or effectiveness.

Rapid Remission in Rheumatoid Arthritis: A Head-to-Head Comparison of Tofacitinib and Upadacitinib

Presenter: Babur Salim.

This real-world comparative cohort study evaluated tofacitinib vs. upadacitinib in biologic- and JAK inhibitor-naïve patients with active RA. The analysis assessed rapid remission within 12 weeks and explored clinical predictors of treatment response, addressing a key evidence gap in head-to-head JAK inhibitor effectiveness.

Among 75 biologic- and JAKi-naïve RA patients (tofacitinib n=44; upadacitinib n=31; females: 73%; mean age: 54 years), 43% achieved rapid remission within 12 weeks, with higher remission rates for tofacitinib vs. upadacitinib (45% vs. 39%). Independent predictors of rapid remission were lower baseline disease activity (aOR 1.8, 95% CI 1.1–2.9; p=0.02), shorter disease duration (aOR 2.1, 95% CI 1.3–3.4; p=0.003), and tofacitinib use (aOR 1.7, 95% CI 1.0–2.8; p=0.04), supporting early intervention and individualized treatment selection.

Real-world head-to-head RA study compared tofacitinib and upadacitinib in biologic- and JAKi-naïve patients. Tofacitinib showed higher rapid remission rates, with early disease and lower baseline disease activity predicting better outcomes.

Comparative Efficacy and Safety of Voclosporin, Belimumab, and Obinutuzumab in Lupus Nephritis: A Systematic Review and Network Meta-Analysis of 9 Randomized Controlled Trials

Presenter: Madhuri Banoth.

This systematic review and network meta-analysis compared voclosporin, belimumab, and obinutuzumab in active lupus nephritis using MMF plus glucocorticoids as a common comparator. The study ranked treatments for renal efficacy and safety and explored outcomes across lupus nephritis classes and treatment subgroups.

In 2,726 LN patients from 9 RCTs, voclosporin (OR 2.58, 95% CI 1.79–3.71; p<0.001), obinutuzumab (OR 2.45, 95% CI 1.66–3.60; p<0.001), and belimumab (OR 1.75, 95% CI 1.26–2.44; p=0.001) improved CRR vs. MMF+GC, with voclosporin ranking highest (SUCRA 71.8%). The safety profile was most favorable for belimumab (rate lower than control); obinutuzumab had the highest serious infection signal (B-cell depletion); SAE rates for voclosporin comparable to MMF+GC. Overall, heterogeneity was low (I²=0-8% across comparisons).

All targeted agents improved CRR in lupus nephritis; voclosporin ranked highest, with treatment response varying by LN class and safety profile, supporting precision-based biologic selection.

Network meta-analysis of active LN showed all 3 targeted therapies improved renal response vs. standard therapy. Voclosporin had the highest SUCRA ranking for complete renal response; however, indirect differences between voclosporin, obinutuzumab, and belimumab were not statistically significant.

Icotrokinra, an IL-23 Receptor Targeted Oral Peptide, in Biologic-Naïve Participants with Active Psoriatic Arthritis: Results Through Week 24 of a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study

Presenter: Joseph F. Merola.

The Phase 3 ICONIC-PsA 1 study evaluated oral icotrokinra, a selective IL-23 receptor inhibitor, in biologic-naïve patients with active PsA inadequately controlled by csDMARDs and/or apremilast. Efficacy through Week 24 was assessed against placebo, with ustekinumab included as a safety reference arm.

552 biologic-naïve PsA patients were randomized; baseline demographics, disease characteristics, and inflammatory burden were balanced across groups. Icotrokinra demonstrated strong efficacy in biologic-naïve PsA, with ACR20 responses of 58% (200 mg; p=0.002 vs. placebo) and 52% (400 mg; p=0.052) vs. 41% with placebo. Higher ACR50 (29% and 23% vs. 16%), ACR70 (13% and 10% vs. 5%), and IGA 0/1 responses (57% and 57% vs. 14%; p<0.001 for both) were observed with icotrokinra, with benefits sustained through Week 24 and balanced AE rates (44%, 52%, 41%, and 51% for ICO 200 mg, ICO 400 mg, placebo, and ustekinumab, respectively).

ICO 200 mg improved joint and skin outcomes vs. placebo at Week 16, with sustained benefits through Week 24. The 400 mg dose offered no added efficacy, while safety profiles remained comparable across treatment groups.

Icotrokinra 200mg met the Week 16 ACR20 endpoint versus placebo. The 400 mg comparison did not reach statistical significance, and secondary endpoint P values were nominal because multiplicity-controlled testing could not proceed. No new safety signals were identified through Week 24.

ACR Convergence 2026, November 6–11, Orlando, Florida.