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Grand RoundsWeekly Evidence Brief

Rheumatology

Edition

30-Second Takeaway

  • b/tsDMARD class in RA shows no clear differential malignancy risk; prioritize patient-specific cancer risk factors instead.
  • Regulatory warnings have reshaped JAK inhibitor use, especially tofacitinib, with greater discontinuation in high-risk RA patients.
  • Short-term high-dose glucocorticoids, not cumulative exposure, dominate ONFH risk in SLE, arguing for peak-dose minimization.

Week ending February 28, 2026

Grand Rounds: Targeted Therapy Safety, Risk Stratification, and Organ Protection in Rheumatology

Malignancy risk is similar across b/tsDMARD classes in RA

THERAPEUTIC ADVANCES IN MUSCULOSKELETAL DISEASEFeb 26, 2026

In this Taiwanese nationwide cohort of 8732 biologic-naïve adults with RA, cancer risk was comparable among TNFi, tocilizumab, abatacept, and tsDMARDs. No statistically significant differences in malignancy incidence appeared over 5-year and extended 18-year follow-up across these treatment groups. Male sex, older age at b/tsDMARD initiation, chronic lung disease, and higher-dose corticosteroid use were independently associated with higher malignancy risk. Conventional DMARD co-therapy and more frequent ambulatory follow-up were linked with lower malignancy risk, likely reflecting better disease control.

Unfavorable social context shortens life expectancy in RA

AMERICAN JOURNAL OF EPIDEMIOLOGYFeb 27, 2026

More than 15,000 adults with RA from China Kadoorie Biobank and UK Biobank were stratified by composite social determinants of health scores. Unfavorable social determinants were associated with substantially higher mortality, with adjusted hazard ratios around 1.6–1.8 versus favorable profiles. At age 45, RA patients with unfavorable social context lost several years of life expectancy, with sex- and country-specific patterns. Phenome-wide analysis identified 51 incident conditions, including heart failure, obstructive chronic bronchitis, and renal failure, with 1.2–5.2-fold higher risks.

Pulmonary involvement is frequent and damaging in AAV

SEMINARS IN ARTHRITIS AND RHEUMATISMFeb 22, 2026

Among 1026 patients with ANCA-associated vasculitis, 81.3% developed pulmonary manifestations during their disease course. Pulmonary involvement was present at onset in 62.7% and recurred in 41.4% of relapse episodes, often with multiple concurrent manifestations. Nodules and cavities, diffuse alveolar hemorrhage, and inflammatory infiltrates were most common; nodules predominated in GPA, hemorrhage in MPA. Overall, 17.4% of those with pulmonary disease accrued permanent pulmonary damage attributed to vasculitis.

Epigenomic maps in primary OA tissues identify effector genes

ANNALS OF THE RHEUMATIC DISEASESFeb 27, 2026

In 314 patients undergoing knee replacement for osteoarthritis, investigators profiled genotype, DNA methylation, and gene expression across multiple primary tissues. They generated genome-wide mQTL maps in cartilage, synovium, infrapatellar fat pad, and blood, plus eQTM maps in cartilage and synovium. Integration with OA GWAS signals revealed widespread variant–methylation and methylation–expression associations relevant to disease biology. Colocalisation analyses highlighted methylation sites with potential causal roles and identified 50 likely effector genes at GWAS loci.

References

Numbered in order of appearance. Click any reference to view details.

Additional Reads

Optional additional studies from this edition.

Edition context

Clinical signal

  • Real-world RA registries refine safety profiles of b/tsDMARDs and JAK inhibitors beyond trial data, directly impacting sequencing decisions.
  • Dose pattern and patient phenotype meaningfully modify treatment-related harm, from GC-induced ONFH to malignancy and JAKi safety concerns.
  • Organ-specific complications in vasculitis, PsA, SLE, and autoimmune disease (lung, bone, eye) require systematic, proactive screening strategies.