Incidence and predisposing factors of extra-articular manifestations in contemporary rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis [RA) is a chronic inflammatory disease, with potential for extra-articular manifestations (ExRA). The incidence and predisposing factors for ExRA and the mortality were evaluated in an early RA inception cohort. METHODS: Patients (n = 1468; 69 % females, mean age (SD) 57.3(16.3) years) were consecutively included at the date of diagnosis, between 1 January 1996 and 31 December 2016, and assessed prospectively. In December 2016 development of ExRA was evaluated by a patient questionnaire and a review of medical records. Cumulative incidence and incidence rates were compared between 5-year periods and between patients included before and after 1 January 2001. Cox proportional hazard regression models were used to identify predictors for ExRA, and models with ExRA as time-dependent variables to estimate the mortality. RESULTS: After a mean (SD) follow-up of 9.3(4.9) years, 238 cases (23.3 %) had ExRA and 151 (14.7 %) had ExRA without rheumatoid nodules. Most ExRA developed within 5 years from diagnosis. Rheumatoid nodules (10.5 %) and keratoconjunctivitis sicca (7.1 %) were the most frequent manifestations, followed by pulmonary fibrosis (6.1 %). The ExRA incidence among more recently diagnosed patients was similar as to the incidence among patients diagnosed before 2001. Seropositivity, smoking and early biological treatment were associated with development of ExRA. After 15 years 20 % had experienced ExRA. ExRA was associated with increased mortality, HR 3.029 (95 % CI 2.177-4.213). CONCLUSIONS: Early development of ExRA is frequent, particularly rheumatoid nodules. Predisposing factors were age, RF positivity, smoking and early biological treatment. The patients with ExRA had a 3-fold increase in mortality.

Pulmonary fibrosis in relation to genetic loci in an inception cohort of patients with early rheumatoid arthritis from northern Sweden.

OBJECTIVES: Pulmonary manifestations in RA are common comorbidities. Interstitial lung disease (ILD), both idiopathic and in RA, has been associated with several genetic variants. We assessed pulmonary fibrosis (PF) in an inception cohort of RA patients in relation to genetic variants and disease-related factors. METHODS: A total of 1466 early RA patients were consecutively included and followed prospectively from the index date until death or 31 December 2016. Clinical and laboratory data and treatment were continuously registered according to the Swedish Rheumatology Quality Register. DNA was available from 1184 patients and 571 151 genome-wide single-nucleotide polymorphisms (SNPs) were analysed. Thirteen identified genetic variants were extracted. At follow-up, the patients answered a questionnaire regarding disease progression and lung involvement that was validated by reviewing medical records and analysing radiological examinations. RESULTS: The prevalence of PF was 5.6% and the annualized incidence rate was 5.0/1000 (95% CI 3.80, 6.54). Four SNPs were associated with PF in RA: rs35705950 [MUC5B; OR 2.5 (95% CI 1.5, 4.0), adjusted P-value = 0.00016, q-value = 0.0021]; rs111521887 [TOLLIP; OR 1.9 (95% CI 1.3, 2.8), adjusted P-value = 0.0014, q-value = 0.0092]; rs2609255 [FAM13A; OR 1.7 (95% CI 1.1, 2.5), adjusted P-value = 0.013, q-value = 0.055] and rs2736100 [TERT; OR 1.5 (95% CI 1.0, 2.2), adjusted P-value = 0.046, q-value = 0.15]. Older age and RF positivity were associated with increased risk, while MTX treatment was associated with a lower risk of PF. CONCLUSIONS: Development of PF in an inception cohort of RA patients was associated with 4 of 12 ILD risk genes. RA-related factors except for age at diagnosis and RF positivity were of limited importance in PF development.