In the 194-patient phase 3 INDIGO trial, weekly subcutaneous obexelimab, a bifunctional antibody that dampens B cells through CD19 and FcγRIIb without depleting them, cut the risk of IgG4-related disease flare by more than half (HR 0.44) and reduced rescue glucocorticoid exposure by about two-thirds over 52 weeks. The comparator was a steroid taper alone, and fewer than 4 in 10 patients on obexelimab reached complete remission.
Growth is the question paediatric rheumatologists ask of any JAK inhibitor, because growth hormone signals through JAK2. In 225 children with JIA followed for a median of 3.6 years on tofacitinib, height stayed close to age-appropriate norms, younger children grew faster than the WHO reference, and IGF-1, IGFBP3 and osteocalcin did not fall. It is a post hoc analysis with no untreated comparator, so it reassures rather than proves.
In 670 biologic-naïve patients with active psoriatic arthritis, the oral TYK2 inhibitor deucravacitinib achieved ACR20 in 54.2% versus 34.1% on placebo at week 16, with gains in skin, function and quality of life sustained to week 52. But the pre-specified radiographic endpoint was negative, the testing hierarchy broke at enthesitis, and the claim of structural protection rests on a post hoc reanalysis.
Fifteen patients with multidrug-resistant RA received blinatumomab at roughly a tenth of the haematology dose. All 15 achieved at least ACR20 and synovial B cells were depleted, but 14 of 15 flared within a median five months. The more provocative observation is what happened next: seven patients responded for over three months to b/tsDMARDs that had already failed them — raising the possibility that partial depletion resensitises rather than resets.
Up to 40% of children with JIA don’t respond to methotrexate, and we currently have no way to know in advance. This three-centre study of 195 patients found that erythrocyte ITPA enzyme activity measured before the first dose separates responders from non-responders, and outperforms genotyping the ITPA variant. But the cutoffs run at 60% sensitivity and 63% specificity — enough to shift a prior, not enough to decide on its own.
An individual patient data meta-analysis of 16 phase 3 trials and 11,883 patients shows JAK inhibitor response falls in a graded way as BMI rises — roughly 18 fewer ACR20 responders per 100 treated at class 3 obesity. Crucially, no such gradient appears in the placebo arms, and within-trial interaction analyses confirm obesity modifies the treatment effect rather than simply marking worse disease.
In a UCL cohort of prolonged SACQ lupus patients — elevated anti-dsDNA and/or low C3 for 6+ months with no clinical activity — 63% flared over a mean 3.3 years. Rising IgG anti-dsDNA and falling C3 at one visit independently predicted flare and sustained activity at the next, including moderate-to-severe disease, in a visit-by-visit longitudinal model. The risk from low C3 rose sharply below 0.9 g/L and flattened above it.
Population-based data from Olmsted County finally give a usable number for how often a seronegative RA diagnosis turns out to be something else: about 13% over ten years, front-loaded into the first five, and most often spondyloarthritis. A quarter achieve sustained drug-free remission lasting a median of 6.3 years, one in five needs a biologic — and nothing measured at baseline predicts which.
Secukinumab doubled sustained remission at 52 weeks in relapsed polymyalgia rheumatica — 41% versus 20% on a prednisone taper alone — and halved the need for escape steroid. But 150 mg worked as well as 300 mg, the component data show the drug maintains remission rather than inducing it, and roughly six in ten treated patients still did not reach the endpoint.
ACPA-positive and ACPA-negative RA take the same total time from first symptom to arthritis — but split it in mirror image. Seropositive patients reach the rheumatologist later and convert faster; seronegative patients arrive sooner and linger, leaving roughly twice as long an actionable window once they are in front of you. Each entity carries its own signature before arthritis exists.