Rheumatology

Implanted vagus nerve stimulation provides durable benefit in b/tsDMARD-refractory RA

RESET-RA randomized 242 RA patients with inadequate response or intolerance to b/tsDMARDs to active versus sham vagus nerve stimulation for 3 months. Active stimulation improved ACR20 at 3 months versus sham (35.2% vs 24.2%; P=0.0209). ACR20 responses rose further with open-label stimulation, reaching about half of completers at 6 and 12 months, indicating durability. Adverse events were similar between arms; serious device-related events were rare, perioperative, and resolved. 1

Early high-dose methotrexate improves glucocorticoid-free remission in newly diagnosed PMR

This 52-week double-blind RCT enrolled recently diagnosed PMR patients on <8 weeks of glucocorticoids using a standardized 24-week taper. Patients were randomized to methotrexate 25 mg/week or placebo, with glucocorticoid-free remission at week 52 as the primary endpoint. Glucocorticoid-free remission occurred in 80% receiving methotrexate versus 46% on placebo, an absolute difference of 34% (one-sided P=0.0042). Despite modest sample size, trial quality and effect size support early high-dose methotrexate as a first-line steroid-sparing strategy. 2

TNF inhibitors show lower serious infection risk than JAK inhibitors in real-world RA

This nationwide Japanese claims cohort compared serious infection risk in 5,018 new RA users of TNF inhibitors versus JAK inhibitors. After propensity score overlap weighting, TNF inhibitor use was associated with lower serious infection risk than JAK inhibitors (HR 0.55; 95% CI 0.39–0.77). Lower risks were also seen for respiratory tract infections, urogenital infections, and sepsis in TNF inhibitor users. Drug-specific analyses suggested relatively higher infection risk with baricitinib and infliximab. 3

JAK inhibitors increase malignancy risk in RA without a clear MACE or VTE excess

This meta-analysis pooled 18 RA trials including 111,260 participants exposed to JAK inhibitors to evaluate malignancy and cardiovascular safety. JAK inhibitors increased risks of overall malignancies, nonmelanoma skin cancer, lung cancer, lymphoma, and several specific tumor types. In contrast, JAK inhibitors did not significantly change risks of major adverse cardiovascular events, venous thromboembolism, or deep vein thrombosis. Trial sequential analysis indicated sufficient evidence, and meta-regression showed no major modification by age, treatment duration, or sample size. 4