ACR 2026 Day 4 Report Save

The last day of ACR 2026 was a half-day but a busy day, with several exciting reports, especially coming from the late-breaking abstracts. See below:

• ALKIVIA — Efgartigimod Becomes the First Positive Phase 3 Drug in IMNM: (Abstract LB24) Dr. Rohit Aggarwal (University of Pittsburgh) presented the phase 3 cohort of the ALKIVIA trial of weekly subcutaneous efgartigimod PH20, the FcRn blocker that lowers IgG and with it pathogenic autoantibodies, added to background therapy with a mandatory steroid taper. In total, 175 patients with immune-mediated necrotizing myopathy (IMNM, n=92), dermatomyositis (DM, n=54) or polymyositis (n=29) were randomized 1:1 to efgartigimod or placebo for 52 weeks, with the primary analysis in IMNM plus DM. Efgartigimod met the primary endpoint: mean Total Improvement Score at week 52 was 48.0 vs 32.6, a 15.4-point difference (95% CI 6.3–24.5; p=0.0011), with benefit from week 4 despite steroid tapering. In IMNM the difference was 14.8 points (45.1 vs 30.2; p=0.0048), with a 22-point higher rate of TIS ≥40, a 5.4-point MMT-8 gain and a 43.5% greater CK reduction. DM showed a similar 14.5-point TIS gain (51.5 vs 37.0) that was not significant in this smaller group (p=0.11), though TIS ≥40 was 27 points higher and CDASI improved 5.6 points. There were no deaths and no new safety signals. This is the first successful phase 3 trial in IMNM, a disease with no approved therapy. Its success in an anti-SRP/HMGCR antibody-driven myopathy is a strong proof of concept for IgG lowering.
• OASIZ-301 — Dazodalibep, a CD40L Blocker in Sjögren’s: (Abstract LB22) Dr. Ghaith Noaiseh (University of Kansas) reported the 48-week phase 3 OASIZ-301 trial of dazodalibep, a non-antibody fusion protein that blocks CD40/CD40L costimulation, in 648 Sjögren’s patients with ESSDAI ≥5. Patients were randomized to dazodalibep 1500 mg IV every 4 weeks, 3000 mg IV every 12 weeks, or placebo. ESSDAI fell by 5.6 and 5.2 points with the two regimens vs 3.8 with placebo (p=0.010), with an effect seen as early as week 4. The monthly dose also improved patient-reported dryness: ESSPRI dryness changed by −2.50 vs −1.33 (p<0.001). Adverse events, serious adverse events and discontinuations were similar to placebo. The systemic effect is modest, but this positive phase 3 makes CD40L blockade a candidate disease-modifying therapy for Sjögren’s, and one that improves dryness as well.
• Afimetoran — An Oral TLR7/8 Inhibitor in SLE: (Abstract LB23) Dr. Kenneth Kalunian (UC San Diego) presented the 48-week phase 2 trial of afimetoran, a once-daily oral inhibitor of TLR7 and TLR8 (TLR7 gain-of-function variants can cause lupus). In all, 248 patients with active SLE on background therapy, with a mandatory steroid taper, were randomized to 2.5, 10 or 30 mg or placebo. SRI-4 at week 48 was 67.8%, 64.1% and 66.1% vs 34.4% with placebo (p<0.001 for each dose), with consistent gains in BICLA, LLDAS, CLASI-50, joints and steroid reduction. The interferon gene score was suppressed by week 2 at every dose, with rising complement and falling anti-dsDNA. Serious adverse events were less frequent than with placebo (5.9% vs 12.9%), and infections were 55–67% vs 53%. The results lacked multiplicity control and showed no dose response, but the roughly 32-point advantage over placebo is striking. Future phase 3 studies in SLE and cutaneous lupus are expected.
• REDUCE-2 — Pozdeutinurad, a New URAT1 Inhibitor, in Gout: (Abstract LB20) Dr. Puja Khanna (University of Michigan) presented the phase 3 REDUCE-2 trial of pozdeutinurad (AR882), a highly selective once-daily URAT1 inhibitor. It randomized 811 gout patients with at least 2 flares in the prior year (mean serum urate 8.4 mg/dL, 26.8% with tophi) 2:2:1 to 75 mg, 50 mg or placebo for 12 months. At month 6, serum urate was below 6 mg/dL in 69.2% and 56.6% vs 8.1% with placebo (p<0.0001), rising to 79.4% and 66.0% in the per-protocol population, and reductions were sustained through month 12. Renal safety, the concern with past uricosurics, was reassuring kidney stones occurred in 0.9% and 1.8% vs 0.6%, and there was very few cases of AKI (0–0.3% vs 0.6%), with overall adverse events similar to placebo (~61%). Pozdeutinurad looks like an effective, kidney-friendly uricosuric, and possible alternative for patients who can’t take xanthine oxidase inhibitors.