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Methotrexate (MTX) monotherapy is a common first treatment for rheumatoid arthritis (RA), but many patients do not respond adequately. In order to identify genetic predictors of response, we have combined data from two consortia to carry out a genome-wide study of response to MTX in 1424 early RA patients of European ancestry. Clinical endpoints were change from baseline to 6 months after starting treatment in swollen 28-joint count, tender 28-joint count, C-reactive protein and the overall 3-component disease activity score (DAS28). No single nucleotide polymorphism (SNP) reached genome-wide statistical significance for any outcome measure. The strongest evidence for association was with rs168201 in NRG3 (p = 10−7 for change in DAS28). Some support was also seen for association with ZMIZ1, previously highlighted in a study of response to MTX in juvenile idiopathic arthritis. Follow-up in two smaller cohorts of 429 and 177 RA patients did not support these findings, although these cohorts were more heterogeneous.

Abstract Background We evaluated the impact of a brief peer-led intervention on COVID-19 vaccination among people who inject drugs (PWID) presenting at syringe services program (SSP) locations in San Diego County, California. Methods Between March and July 2022, PWID aged ≥18 years without recent voluntary COVID-19 testing who were not up to date on COVID-19 vaccinations received a single-session motivational interviewing intervention (LinkUP) or an attention-matched didactic control condition from trained peer counselors at SSP sites randomized by week. Following either 30-minute session, counselors offered referrals to local vaccination services. Multivariable log binomial regression via generalized estimating equations assessed LinkUP effects on (1) acceptance of COVID-19 vaccination referrals immediately postintervention and (2) COVID-19 vaccine uptake at 6-month follow-up. Results COVID-19 vaccination outcomes were obtained on 135 (90.6%) of 149 participants. In multivariable analysis, participants receiving LinkUP had greater acceptance of COVID-19 vaccination referrals than controls (adjusted relative risk, 3.50; 95% CI, 1.01–12.2) and were marginally more likely to report receiving a new COVID-19 vaccine dose (adjusted relative risk, 1.57; 95% CI, .99–2.48). After 6 months, 20% reported receiving a new vaccine dose; however, if COVID-19 vaccine had been available at SSPs, this proportion could have been as high as 34.3% (45.3% LinkUP vs 24.3% control; P = .01). Conclusions A brief peer-led SSP-based intervention significantly improved COVID-19 vaccination among PWID. Further improvements could likely be obtained by supporting SSPs to offer COVID-19 vaccination on-site instead of relying on referrals. Clinical Trials Registration ClinicalTrials.gov NCT05181657. People who inject drugs experience a disproportionate burden of COVID-19. Leveraging community and academic expertise and confidence in peers and syringe services programs, this pilot randomized controlled trial evaluated the efficacy of a novel intervention to increase COVID-19 vaccination among people who inject drugs.