Response to interleukin-6 receptor antagonists in patients with rheumatoid arthritis is independent of the number of prior used TNF inhibitors: A systematic review and metaanalysis.

OBJECTIVE: To investigate whether early response to tocilizumab (TCZ) and sarilumab (SAR) therapy in patients with active rheumatoid arthritis (RA) is influenced by previous use of biologic agents. METHODS: We performed a systematic literature review and a meta-analysis of original studies that analyzed the effectiveness of TCZ or SRL in subgroups of RA patients, including biologic-naïve patients versus those with inadequate response to at least one biologic DMARD (bDMARD), and patients with failure to 1 versus≥2 bDMARDs. RESULTS: The study selection process finally included 17 articles corresponding to 14 studies, including 7 randomized controlled trials (RCTs). Although the existing literature that compared the response in biologic-naïve patients versus those with inadequate response to at least one bDMARD showed conflicting results, meta-analysis of 6 published studies revealed a significantly higher likelihood of remission (RR=1.3; 95% CI: 1.2-1.5) and low activity disease (RR=1.3; 95% CI: 1.2-1.4) in the biologic-naïve group at week 24. However, differences between groups were not clinically meaningful in all studies and not always maintained after 6 to 12months of treatment. In addition, data from RCT RADIATE and TARGET suggest that the response to IL-6 pathway inhibitors seems to be similar, regardless of the number of tumor necrosis factor inhibitors (TNFis) previously tested. CONCLUSION: Disease activity was more rapidly reduced in the early stages of treatment in biologic-naïve patients. However, near similar efficacy can be expected in patients who experienced a failure of at least one bDMARD (mainly TNFis) beyond the first 6 to 12months of treatment, suggesting that the response occurs independently of the number of prior TNFis.

Pulmonary arterial hypertension in adult-onset Still's disease: A case series and systematic review of the literature.

OBJECTIVE: To investigate the prevalence, clinical characteristics and prognosis of pulmonary arterial hypertension (PAH) in adult onset Still's disease (AOSD). METHODS: We retrospectively reviewed all patients with AOSD diagnosed during a 33-year period in 2 referral tertiary care hospitals, selecting for analysis those who presented PAH confirmed as by right heart catheterization. A systematic review of the literature (PubMed 1990 to July 2018) was also performed, in order to determine the prognosis and the most appropriate treatment strategy for this complication. RESULTS: The overall prevalence of PAH in our AOSD population was 4.8% (2/41). Including our 2 cases, 20 well-documented patients have been reported. PAH may complicate AOSD at any time during its course, and usually occurs in patients who have persistent and severe disease, with a considerable frequency (35%) of previous or concomitant severe clinical complications. In all cases, the etiology of pulmonary hypertension was a group 1 PAH based on the 2015 ESC/ERS guidelines. Most patients in this series had advanced WHO functional classes III-IV at the time of PAH diagnosis, reflecting an important diagnostic delay. Thirty-three percent of patients had a poor outcome despite the therapy, with a mortality rate that reached 22%. The therapeutic strategy that achieved the best results was the use of glucocorticoids, immunosuppression and PAH-specific vasodilator therapy. CONCLUSION: HAP is an under-recognized complication of AOSD that should be kept in mind in the differential diagnosis of those patients who experience dyspnea on exertion or a decrease in exercise tolerance.