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Introduction: Hydroxychloroquine (HCQ) exerts a large reduction of cardiovascular risk in patients with inflammatory diseases, but the mechanisms are not fully known. The aim of this study was to study potential mechanisms for this.

Methods: This interventional study (EudraCT 2014-005418-45) in 30 patients (23 with rheumatoid arthritis, 7 with systemic lupus erythematosus) investigates the effects of HCQ on cardiovascular risk factors and arterial stiffness in patients with inflammatory disease. Blood lipids, blood pressure, blood glucose, glycated haemoglobin (HbA1c) and arterial stiffness was assessed at initiation, after four weeks of treatment and after eight weeks of treatment with 200 mg HCQ daily.

Results: After four weeks of treatment with HCQ, total cholesterol had decreased from 5.4 mmol/L to 5.1 mmol/L (p<0.001), low-density lipoproteins from 3,0 mmol/L to 2.7 mmol/L (p<0.001) and apolipoprotein B from 0.96 g/L to 0.90 g/L (p<0.01). Those levels remained unchanged after eight weeks of treatment with HCQ. Levels of triglycerides, high-density lipoproteins and apolipoprotein A1 remained unchanged during the study. HbA1c decreased in most patients, especially in patients with high levels at start of HCQ, but increased HbA1c was seen in patients with low levels at start of treatment with HCQ. No significant effect was seen on blood pressure or any measure of arterial stiffness.

Conclusion: This study does not identify the mechanisms of cardiovascular risk reduction from HCQ. Arterial stiffness is not affected by HCQ. The impact of HCQ on HbA1c and blood lipids is rapid, but of modest magnitude, and these effects do not fully explain the reduced risk of cardiovascular disease seen in observational studies. The mechanisms of cardiovascular risk reduction from HCQ are yet not completely known.

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.

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.