The effect of antimalarials on the safety and persistence of treatment with biologic agents or Janus kinase inhibitors in rheumatoid arthritis.

OBJECTIVES: To test the association of use of antimalarials with the overall safety of treatment in RA patients receiving one or multiple courses of biologic (b)DMARDs or a Janus kinase inhibitor (JAKi). METHODS: BiobadaBrasil is a multicentric registry-based cohort study of Brazilian patients with rheumatic diseases starting their first bDMARD or JAKi. The present analysis includes RA patients recruited from January 2009 to October 2019, followed up over one or multiple (up to six) courses of treatment (latest date, 19 November 2019). The primary outcome was the incidence of serious adverse events (SAEs). Total and system-specific adverse events (AEs) and treatment interruption served as secondary outcomes. Negative binomial regression with generalized estimating equations (to estimate multivariate incidence rate ratios, mIRR) and frailty Cox proportional hazards models were used for statistical analyses. RESULTS: The number of patients enrolled was 1316 (2335 treatment courses, 6711 patient-years [PY]; 1254.5 PY on antimalarials). The overall incidence of SAEs was 9.2/100 PY. Antimalarials were associated with reduced risk of SAEs (mIRR: 0.49; 95% CI: 0.36, 0.68; P < 0.001), total AEs (0.68; 95% CI: 0.56, 0.81; P < 0.001), serious infections (0.53; 95% CI: 0.34, 0.84; P = 0.007) and total hepatic AEs (0.21; 95% CI: 0.05, 0.85; P = 0.028). Antimalarials were also related to better survival of treatment course (P = 0.003). There was no significant increase in the risk of cardiovascular AEs. CONCLUSION: Among RA patients on treatment with bDMARDs or JAKi, concomitant use of antimalarials was associated with reduced the incidence of serious and total AEs and with longer treatment course survival.

Acquired factor XI inhibitor in systemic lupus erythematosus--case report and literature review.

OBJECTIVES: Rare patients with systemic lupus erythematosus (SLE) patients exhibit anticoagulants that interfere in the earlier stages of the intrinsic coagulation pathway, such as those involving factor XI (FXI). The objectives of our study were to describe the presence of an acquired inhibitor to FXI causing a life-threatening bleeding disorder in an SLE patient and to review the association of this coagulopathy with SLE. METHODS: We describe the clinical presentation of an SLE patient with an acquired FXI inhibitor. We reviewed the scientific literature using the MEDLINE database searching the following combinations of terms: "SLE and Factor XI," "SLE and Factor XI inhibitor," and "Factor XI inhibitor," from 1964 to 2007. RESULTS: A 20-year-old woman with a 6-year history of SLE was admitted to the hospital because of severe life-threatening abdominal bleeding due to a ruptured ovarian cyst. This hemorrhagic event was related to the presence of an FXI inhibitor. We reviewed another 13 SLE patients with this condition, 8 of whom had bleeding events. Most patients had manifestations of active SLE, and prednisone was used as the primary treatment. CONCLUSIONS: SLE activity seems to be associated with the production of antibodies directed against FXI, which may cause important coagulopathies, especially bleeding events. The inhibitor disappeared after immunosuppressive therapy for SLE in most cases, suggesting that the appearance of this inhibitor is immune mediated. Although the majority of cases with the FXI inhibitor are not fatal, it should be suspected and investigated in SLE patients, especially those with abnormal clotting tests.