Introduction/Objective: The efficacy of biologic therapy in the treatment of rheumatoid arthritis (RA) has been well-established but, in practice, a quarter of patients will either not respond to the first biologic agent or will suffer an adverse event requiring a switch to a different drug. While clinical guidelines exist to help guide therapy and previous studies have examined sequential use of anti-TNF agents, there is little data to inform a multiple switch strategy. Our aim was to measure the efficacy of multiple switches of biologic in severe refractory RA. Methods: We enrolled 111 patients whose therapy with one anti-TNF agent had failed in this open-label observational study. These patients were all treated with a second biologic agent and 27 ultimately required treatment with a third. The response to the therapy and disease activity were assessed at 6 and 12 months after each switch. Results: The remission rates at 6 months were lower than previously reported and the initiation of a second biologic agent resulted in significant improvement at 12 months, including DAS remission in 36% of patients. The response in those receiving a third biologic was less pronounced, as might be expected in this relatively treatment-refractory population. In this group, only patients treated with tocilizumab had maintained remission at one year. Conclusion: Patients who do not respond to an anti-TNF agent often benefit from being switched to a second, or even third, biologic. Importantly, it may take longer than expected to fully assess the effectiveness of a second or third agent in patients with refractory disease.

Background and Objectives: In patients with COVID-19, high-flow nasal cannula (HFNC) and continuous positive airway pressure (CPAP) are widely applied as initial treatments for moderate-to-severe acute hypoxemic respiratory failure. The aim of the study was to assess which respiratory supports improve 28-day mortality and to identify a predictive index of treatment response. Materials and Methods: This is a single-center retrospective observational study including 159 consecutive adult patients with COVID-19 and moderate-to-severe hypoxemic acute respiratory failure. Results: A total of 159 patients (82 in the CPAP group and 77 in the HFNC group) were included in the study. Mortality within 28 days was significantly lower with HFNC compared to CPAP (16.8% vs. 50%), while ICU admission and tracheal intubation within 28 days were significantly higher with CPAP compared to HFNC treatment (32% vs. 13%). We identified an index for survival in HFNC by including three variables easily available at admission (LDH, age, and respiratory rate) and the PaO₂/FiO₂ ratio at 48 h. The index showed high discrimination for survival with an AUC of 0.88, a negative predictive value of 86%, and a positive predictive value of 95%. Conclusions: Treatment with HFNC appears to be associated with greater survival and fewer ICU admission than CPAP. LDH, respiratory rate, age, and PaO₂/FiO₂ at 48 h were independently associated with survival and an index based on these variables allows for the prediction of treatment success and the assessment of patient allocation to the appropriate intensity of care after 48 h. Further research is warranted to determine effects on other outcomes and to assess the performance of the index in larger cohorts.