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.

Increased Prevalence of Moderate to Severe Mitral and Aortic Valve Dysfunction in Systemic Sclerosis: A Case-control Study.

OBJECTIVE: To investigate the prevalence, severity, and associated clinical factors of mitral and aortic valvular involvement in patients with systemic sclerosis (SSc). METHODS: Our case-control study included 172 patients with SSc and 172 non-SSc adults without known cardiac disease matched by age, sex, and prevalence of cardiovascular (CV) risk factors. The screening of mitral and aortic valvular involvement was performed by transthoracic Doppler echocardiogram. The prevalence of aortic stenosis (AS) was also compared with that reported in a population-based study performed in our community during the same period. RESULTS: Patients with SSc showed an almost 5-fold increased prevalence of moderate to severe mitroaortic valve dysfunction compared to non-SSc controls (OR 4.60, 95% CI 1.51-13.98; P = 0.003). The most common lesion was mitral regurgitation (MR), which was observed in 5.2% of patients, followed by AS in 3.5%, and aortic regurgitation (AR) in 1.7%. Analyzing the different types of valvular lesion separately, we observed a significantly higher frequency of MR compared to controls (OR 4.69, 95% CI 1.12-22.04; P = 0.032), as well as a higher frequency of AS in the 65-75 (OR 7.51, 95% CI 1.22-46.23, P = 0.01) and 76-85 age groups (OR 3.53, 95% CI 1.03-12.22, P = 0.043) when compared to the general population in our community. CONCLUSION: We found an increased prevalence of moderate to severe MR and AS in SSc compared to age-matched non-SSc controls with similar CV comorbidities. While results from this study do not allow for establishing a direct causal relationship, they strongly support the contribution of SSc-specific factors in the development of these complications.

Rituximab as a rescue treatment added on mycophenolate mofetil background therapy in progressive systemic sclerosis associated interstitial lung disease unresponsive to conventional immunosuppression.

OBJECTIVE: To test whether the use of rituximab (RTX) is effective and safe as a rescue therapy add-on treatment to mycophenolate (MMF) in patients with progressive systemic sclerosis-associated interstitial lung disease (SSc-ILD) in whom conventional immunosuppressants (IS) have failed. METHODS: Longitudinal retrospective observational study of a cohort of patients with SSc-ILD that started treatment with RTX due to ongoing lung function impairment despite treatment with glucocorticoids and IS (cyclophosphamide and/or MMF). All patients were treated with 2 or more cycles of RTX and evaluated for at least 12 months. RESULTS: Twenty-four patients were included. Before initiation of RTX the mean decline in%pFVC and %pDLCO during the previous 2 years (delta) was -12.9% and -12.5%, respectively. After 1 year of treatment with RTX, a significant improvement in %pFVC (∆+8.8% compared to baseline, 95% CI: -13.7 to -3.9; p = 0.001) and%pDLCO (∆+4.6%, 95% CI: -8.2 to -0.8; p = 0.018) was observed. In addition, there was a significant reduction in the median dose of prednisone and it could be suspended in 25% of patients. At 2 years of treatment, RTX had been discontinued in 9 patients (due to adverse events in 3 cases and inefficacy in 6). In the 15 patients (62.5%) that completed 24 months of therapy, the statistically significant amelioration in pulmonary function test parameters was maintained: ∆%pFVC: +11.1% (95% CI: -17.6 to -4.5; p = 0.003) and ∆%pDLCO: +8.7% (95% CI: -13.9 to -8.3; p = 0.003). CONCLUSION: Based on our results, RTX's use as an add-on treatment to MMF appears to be effective as a rescue therapy in patients with a more aggressive SSc-ILD phenotype.

Development of leprosy in a patient with rheumatoid arthritis during treatment with etanercept: a case report.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder. There is a clear association between some disease-modifying drugs used to treat RA and infection. The introduction of the anti-tumor necrosis factor (TNF) therapies has improved the outcome of severe RA. The TNF-antagonism may increase susceptibility to granulomatous pathogens such as Mycobacterium tuberculosis, Listeria monocytogenes, and Histoplasma capsulatum. METHODS: We report the case of a 37-year-old woman with RA receiving an anti-TNF agent, who developed a rash on her back and both legs, which was finally diagnosed as tuberculoid leprosy. RESULTS: This is the first case of leprosy due to anti-TNF therapy reported in Europe. CONCLUSIONS: Clinicians should be aware of this and other types of atypical and serious infections that patients may suffer from when treated with anti-TNF agents.