Does persistence to methotrexate treatment in early rheumatoid arthritis have a familial component?

Funding Information: Open access funding provided by Karolinska Institute. HW received support for the project from Stiftelsen Anna och Emil Olssons fond, Reumatikerförbundet [grant no R-940868]; Stiftelsen Professor Nanna Svartz Fond [grant no 2020-00334]; Kung Gustav V:s 80 year foundation [grant no FAI-2020-0666]; Karolinska Institutet foundations [grant no 2020-02508 and 2020-02398]. TF and SS were supported by the Swedish Research Council [DNR 2016-01355 and DNR 2018-02803, respectively]. JA was supported by the Swedish Research Council; Nordforsk; Vinnova; Region Stockholm/Karolinska Institutet Funds (ALF) and the Swedish Heart Lung Foundation. Publisher Copyright: © 2022, The Author(s).Objectives: To assess whether persistence to treatment with methotrexate (MTX) in early rheumatoid arthritis (RA) is shared among first-degree relatives with RA and to estimate any underlying heritability. Methods: First-degree relative pairs diagnosed with RA 1999–2018 and starting MTX (in monotherapy) as their first disease-modifying anti-rheumatic drug (DMARD) treatment were identified by linking the Swedish Rheumatology Quality Register to national registers. Short- and long-term persistence to MTX was defined as remaining on treatment at 1 and 3 years, respectively, with no additional DMARDs added. We assessed familial aggregation through relative risks (RR) using log-binomial regression with robust standard errors and estimated heritability using tetrachoric correlations. We also explored the familial aggregation of EULAR treatment response after 3 and 6 months. To mimic the clinical setting, we also tested the association between having a family history of MTX persistence and persistence within the index patient. Results: Familial persistence was not associated with persistence at 1 (RR=1.02, 95% CI 0.87–1.20), only at 3 (RR=1.41, 95% CI 1.14–1.74) years. Heritability at 1 and 3 years was estimated to be 0.08 (95% CI 0–0.43) and 0.58 (95% CI 0.27–0.89), respectively. No significant associations were found between family history and EULAR response at 3 and 6 months, neither overall nor in the clinical setting analysis. Conclusions: Our findings imply a familial component, including a possible genetic element, within the long-term persistence to MTX following RA diagnosis. Whether this component is reflective of characteristics of the underlying RA disease or determinants for sustained response to MTX in itself will require further investigation.Peer reviewe

Incidence and prevalence of systemic sclerosis in Sweden, 2004–2015, a register-based study

Objectives: we aim to present an in-depth report of the incidence and prevalence of systemic sclerosis (SSc) in Sweden in a nation-wide register-based study covering the entire Swedish population Methods: each individual residing in Sweden is given a unique personal identity number. We linked the National Patient Register and the Total Population Register to identify 1) patients with prevalent SSc on 2015–12–31 and 2) patients with incident SSc during the time period 2004–2015 based on ICD-10 codes. We estimated prevalence and incidence overall and stratified on age, sex, and county. Results: we identified 1774 prevalent cases, median age was 65 years (IQR 19.2) and 84% were women. The point prevalence estimate was 22.7 per 100,000 (95%CI 13.3–32.0). 1139 individuals were newly diagnosed with SSc during 2004–2015 with a median age of 60 years (IQR 20.6) and 80% were women. The mean standardized incidence was 11.9 per 1,000,000 person-years (95%CI 5.1–18.7). The annual incidence remained stable over the study period. Women had five times higher incidence and prevalence than men. The highest prevalence stratified by age strata was observed in the group aged 70–79. Conclusion: SSc incidence and prevalence in Sweden are comparable to estimates from southern Europe, as opposed to the previous assumption of lower occurrence in northern Europe. We further observe that SSc incidence has been rather constant throughout recent years in Sweden with no obvious increase