The Efficacy of Sequential Biologic Agents in Refractory Rheumatoid Arthritis after Failure of Initial DMARD and anti-Tumor Necrosis Factor Therapy

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.

Can Chronic Anti-Tumor Necrosing Factor Therapy and Colic Polyps Overwhelm a Normal Functioning Mitral Valve? A Case Report of An Endocarditis Complicated By A Ruptured Intracranial Mycotic Aneurysm

Background Rapid identification of endocarditis is challenging but also an important opportunity to change disease course. This is especially true when immunosuppression undermines diagnosis by mitigating symptoms that commonly accompany infectious disease, sometimes in the absence of predisposing heart valve disease as in this case presented here. Case summary A middle-aged man with chronic etanercept treatment for ankylosing spondylitis, with previously well-documented normal cardiac valves, presented with afebrile chills, night sweating, weight loss, and a new mitral regurgitation at auscultation. This Streptococcus bovis-related endocarditis, in the presence of benign colic polyps, rapidly became complicated by a ruptured infectious intracranial mycotic aneurysm. The patient was successfully cured by endovascular embolisation. Severe mitral regurgitation required an uneventful mitral annuloplasty 1 month thereafter. Discussion Immunosuppression from etanercept treatment was likely responsible for this unspecific clinical presentation and potentially devastating intracranial mycotic aneurysm. This complication is infrequently reported within 6 months of anti-tumor necrosing factor therapy initiation but occurred after more than 11 years of therapy in our patient. This case is a timely reminder of the clinical challenges of endocarditis in immunosuppressed patients and highlights a potential long-term complication of etanercept.

Association between choriocapillaris flow deficit and choroidal neovascularization activity in eyes with myopic choroidal neovascularization

Although choriocapillaris flow deficit (CFD) around choroidal neovascularization (CNV) is less associated with CNV activity in myopic eyes, no reports are investigating its size as an indicator of CNV activity. We investigated the relationship between CFD and high myopia-related CNV. In this retrospective, observational study, patients underwent optical coherence tomography angiography (OCTA) with split-spectrum amplitude-decorrelation angiography for diagnosing pathological myopic CNV (mCNV); CFD features around CNV margins were evaluated. Of the 33 eyes (30 patients), 11 (33.3%) had active mCNV, and 22 (66.7%) had inactive CNV. Six eyes (18.2%) were treatment-naïve, while the remainder previously underwent anti-vascular endothelial growth factor therapy. On OCTA, blood flow signals were detected in CNV in the outer retinal layer in 28 (84.8%) eyes, including all active cases (11 cases) and 17 (77.3%) of 22 inactive cases. CNV flow signal size correlated significantly with activity (P < 0.001). CFD around CNV was observed in 24 eyes (72.7%), including all active cases (11 cases) and 13 (59.1%) of 22 inactive cases. CFD size correlated significantly with CNV activity (P < 0.001). The size of both the CFD area around CNV and CNV flow signal area are useful indicators of CNV activity in eyes with mCNV, which may help determine treatment timing.

COVID-19 and Outcomes in Patients With Inflammatory Bowel Disease: Systematic Review and Meta-Analysis

Background Our understanding of coronavirus disease 2019 (COVID-19) and its implications for patients with inflammatory bowel diseases (IBD) is rapidly evolving. We performed a systematic review and meta-analysis to investigate the epidemiology, clinical characteristics, and outcomes in IBD patients with COVID-19. Methods We searched PubMed, EMBASE, Cochrane Central, Clinicaltrials.gov, Web of Science, MedRxiv, and Google Scholar from inception through October 2020. We included studies with IBD patients and confirmed COVID-19. Data were collected on the prevalence, patient characteristics, pre-infection treatments for IBD, comorbidities, hospitalization, intensive care unit (ICU), admission, and death. Results Twenty-three studies with 51,643 IBD patients and 1449 with COVID-19 met our inclusion criteria. In 14 studies (n = 50,706) that included IBD patients with and without COVID-19, the prevalence of infection was 1.01% (95% confidence interval [CI], 0.92-1.10). Of IBD patients with COVID-19, 52.7% had Crohn’s disease, 42.2% had ulcerative colitis, and 5.1% had indeterminate colitis. Nine studies (n = 687) reported outcomes according to IBD therapy received. Compared with patients on corticosteroids, those on antitumor necrosis factor (anti-TNF) therapy had a lower risk of hospitalization (risk ratio [RR], 0.24; 95% CI, 0.16-0.35; P &lt; .01; I2 = 0%) and ICU admission (RR, 0.10; 95% CI, 0.03-0.37; P &lt; .01) but not death (RR, 0.16; 95% CI, 0.02-1.71; P = .13; I2 = 39%). Compared with patients on mesalamine, those on antitumor necrosis factor therapy had a lower risk of hospitalizations (RR, 0.37; 95% CI, 0.25-0.54), ICU admissions (RR, 0.20; 95% CI, 0.07-0.58), and death (0.21; 95% CI, 0.04-1.00). Comparing patients on immunomodulators vs mesalamine or anti-TNF therapy, there was no difference in these outcomes. Conclusions The prevalence of COVID-19 in IBD patients was low. Use of corticosteroids or mesalamine was significantly associated with worse outcomes, whereas use of anti-TNFs was associated with more favorable outcomes. Further investigation clarifying the mechanisms of these disparate observations could help identify risk and adverse outcome-mitigating strategies for patients with IBD.