ADVANCE OUTCOMES is a phase 3 trial of once-daily oral ralinepag, a prostacyclin IP receptor agonist, added to background therapy in pulmonary arterial hypertension. It cut first clinical worsening by 55% (HR 0.45) — but the effect was carried entirely by softer composite components, with death and hospitalisation unchanged, and 19% discontinued for adverse events. CTD-PAH made up 29% of the cohort as a prespecified stratum.
Final 24-month data from APPLAUSE-IgAN: the oral factor B inhibitor iptacopan roughly halved the rate of eGFR decline in high-risk IgA nephropathy (−3.10 vs −6.12 ml/min/1.73 m²/year) and cut hard kidney-failure events from 33.5% to 21.4%, converting an accelerated approval based on proteinuria into evidence on preserved kidney function — with serious infection the trade-off to manage.
Five-year data from the TREAT EARLIER trial show that a time-limited intervention (one glucocorticoid injection plus 12 months of methotrexate) in clinically suspect arthralgia produced durable benefit in ACPA-negative individuals at increased risk — RA in 9% vs 32%, NNT 4 — but nothing lasting in ACPA-positive individuals, splitting the at-risk phase into two diseases with two different answers.
A population-based MRI study of 11,163 German adults found sacroiliac joint bone marrow oedema in about one in three people — roughly 50 times the prevalence of axial spondyloarthritis. The signal tracked with BMI, occupational loading, age and, in women, pregnancy, while chronic back pain barely moved the rate, providing the missing denominator for interpreting a positive SIJ MRI.
RHO is a phase 2 proof-of-concept RCT of the FcRn antagonist efgartigimod in Sjögren’s disease, testing whether removing pathogenic IgG autoantibodies improves disease. It met its exploratory objective (CRESS response 45.5% vs 11.1% at week 24) with deep, selective IgG reduction — but systemic activity improved while patient-reported symptoms did not, and the tiny sample means this justifies phase 3, not practice change.
ALLEGORY is a phase 3 RCT of the type II anti-CD20 antibody obinutuzumab added to standard therapy in active non-renal SLE. It met its primary endpoint (SRI-4 76.7% vs 53.5% at week 52) and all five key secondary endpoints, achieving both steroid-sparing and a ~40% reduction in flare hazard — reinforcing that depth of B-cell depletion matters and that type II succeeds where rituximab failed.
WILLOW Cohort A is the first placebo-controlled RCT of a TLR7/8 inhibitor in lupus: the oral agent enpatoran met its primary endpoint with a dose-dependent reduction in cutaneous disease activity (CLASI-A) at 16 weeks, and — the headline — rapidly and reversibly switched off the skin type I interferon signature, pinning TLR7/8 as an upstream driver of cutaneous IFN activation. Steroid-sparing was not demonstrated.
RepurpSS-II is a phase 2b, placebo-controlled RCT of leflunomide plus hydroxychloroquine in active systemic Sjögren’s disease, given without any background immunomodulatory therapy. The combination met its primary endpoint — a clinically meaningful ESSDAI improvement (−4.14) at 24 weeks, replicating RepurpSS-I — but dryness and patient-reported symptoms (ESSPRI) did not separate from placebo.
SELECT-SWITCH is the first double-blind RCT to test mechanism-of-action switching (to the JAK inhibitor upadacitinib) versus cycling to a second TNF inhibitor (adalimumab) after a first TNFi fails in RA. At 12 weeks, upadacitinib roughly doubled low-disease-activity rates and beat adalimumab on the primary endpoint and 4 of 5 ranked secondaries — though HAQ-DI function did not separate and safety was comparable.
A combined individual-patient-data analysis of the NORD-STAR and BeSt trials shows that where early RA is distributed carries prognostic signal: hand-dominant disease (JIP-Hand) predicts better treatment response and polyarthritis (JIP-Poly) worse — independent of sex and serology, and equally across csDMARDs and bDMARDs, with ACPA/RF showing no association with short-term activity response.