SARS-CoV-2 Infection and COVID-19 Outcomes in Rheumatic Diseases: A Systematic Literature Review and Meta-Analysis.

OBJECTIVE: The relative risk of SARS-CoV-2 infection and COVID-19 disease severity among people with rheumatic and musculoskeletal diseases (RMDs) compared to those without RMDs is unclear. This study was undertaken to quantify the risk of SARS-CoV-2 infection in those with RMDs and describe clinical outcomes of COVID-19 in these patients. METHODS: We conducted a systematic literature review using 14 databases from January 1, 2019 to February 13, 2021. We included observational studies and experimental trials in RMD patients that described comparative rates of SARS-CoV-2 infection, hospitalization, oxygen supplementation/intensive care unit (ICU) admission/mechanical ventilation, or death attributed to COVID-19. Methodologic quality was evaluated using the Joanna Briggs Institute critical appraisal tools or the Newcastle-Ottawa scale. Risk ratios (RRs) and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated, as applicable for each outcome, using the Mantel-Haenszel formula with random effects models. RESULTS: Of the 5,799 abstracts screened, 100 studies met the criteria for inclusion in the systematic review, and 54 of 100 had a low risk of bias. Among the studies included in the meta-analyses, we identified an increased prevalence of SARS-CoV-2 infection in patients with an RMD (RR 1.53 [95% CI 1.16-2.01]) compared to the general population. The odds of hospitalization, ICU admission, and mechanical ventilation were similar in patients with and those without an RMD, whereas the mortality rate was increased in patients with RMDs (OR 1.74 [95% CI 1.08-2.80]). In a smaller number of studies, the adjusted risk of outcomes related to COVID-19 was assessed, and the results varied; some studies demonstrated an increased risk while other studies showed no difference in risk in patients with an RMD compared to those without an RMD. CONCLUSION: Patients with RMDs have higher rates of SARS-CoV-2 infection and an increased mortality rate.

COVID-19 in Pregnant Women With Rheumatic Disease: Data From the COVID-19 Global Rheumatology Alliance.

OBJECTIVE: To describe coronavirus disease 2019 (COVID-19) and pregnancy outcomes in patients with rheumatic disease who were pregnant at the time of infection. METHODS: Since March 2020, the COVID-19 Global Rheumatology Alliance has collected cases of patients with rheumatic disease with COVID-19. We report details of pregnant women at the time of COVID-19 infection, including obstetric details separately ascertained from providers. RESULTS: We report on 39 patients, including 22 with obstetric detail available. The mean and median age was 33 years, range 24-45 years. Rheumatic disease diagnoses included rheumatoid arthritis (n = 9), systemic lupus erythematosus (n = 9), psoriatic arthritis/other inflammatory arthritides (n = 8), and antiphospholipid syndrome (n = 6). Most had a term birth (16/22), with 3 preterm births, 1 termination, and 1 miscarriage; 1 woman had yet to deliver at the time of report. One-quarter (n = 10/39) of pregnant women were hospitalized following COVID-19 diagnosis. Two of 39 (5%) required supplemental oxygen (both hospitalized); no patients died. The majority did not receive specific medication treatment for their COVID-19 (n = 32/39, 82%), and 7 patients received some combination of antimalarials, colchicine, anti-interleukin 1ß, azithromycin, glucocorticoids, and lopinavir/ritonavir. CONCLUSION: Women with rheumatic diseases who were pregnant at the time of COVID-19 had favorable outcomes. These data have limitations due to the small size and methodology; however, they provide cautious optimism for pregnancy outcomes for women with rheumatic disease particularly in comparison to the increased risk of poor outcomes that have been reported in other series of pregnant women with COVID-19.

Belimumab and Rituximab in Systemic Lupus Erythematosus: A Tale of Two B Cell-Targeting Agents.

Given the centrality of B cells to systemic lupus erythematosus (SLE), it stands to reason that a candidate therapeutic agent that targets B cells could be efficacious. Both rituximab, a monoclonal antibody (mAb) that binds to CD20 on the surface of B cells, and belimumab, a mAb that binds and neutralizes the B cell survival factor BAFF, have been extensively studied for the treatment of SLE. Despite the greater ability of rituximab to deplete B cells than that of belimumab, randomized controlled trials of rituximab in SLE failed to reach their primary clinical endpoints, whereas the primary clinical endpoints were reached in four independent phase-III clinical trials of belimumab in SLE. Accordingly, belimumab has been approved for treatment of SLE, whereas use of rituximab in SLE remains off-label. Nevertheless, several case series of rituximab have pointed to some utility for rituximab in treating SLE. In this review, we provide a concise summary of the factors that led to belimumab's success in SLE as well an analysis of the elements that may have contributed to the lack of success seen in the rituximab randomized controlled trials in SLE.

A patient with primary Sjogren's syndrome, cystic lung disease, and MALT lymphoma treated successfully with rituximab: a case-based review.

Primary Sjogren's syndrome (pSS) can have a myriad of presentations, ranging from mild xerostomia to more diffuse systemic involvement. It is well established that pSS is associated with a variety of pulmonary pathologies, and it is also known that pSS patients are at higher risk for lymphoma development. Here, we present an unusual case of a woman with primary Sjogren's syndrome who had both diffuse cystic lung disease as well as extranodal MALT lymphoma, successfully treated for both conditions with the CD-20 monoclonal antibody rituximab.

The safety of belimumab for the treatment of systemic lupus erythematosus.

Introduction: Systemic lupus erythematosus (SLE) is a systemic autoimmune inflammatory disease with extensive clinical variability. In 2011, the anti-BAFF monoclonal antibody, belimumab, became the first FDA-approved drug for SLE in 50+ years. As with all immunomodulating medications, the benefits must be weighed against the adverse side effects. This is especially pertinent for SLE patients, given the chronic nature of their disease and their need for long-term treatment. The focus of the present review is the safety of belimumab, including data gleaned from clinical trials, their open-label extensions, and 'real-world' clinical settings.Areas covered: Safety data from phase I, phase II, phase III, extension open-label trials, and 'real-world' observational studies of belimumab are reviewed and discussed.Expert opinion: As the only FDA-approved treatment for SLE in the past 60+ years, belimumab has demonstrated significant, albeit modest, efficacy and a reassuring safety profile. Long-term data to date show that it is well-tolerated with a low risk of side effects, even when administered for up to 13 years. Given that belimumab allows providers to decrease daily corticosteroid doses over time (and, thereby, decrease the serious risks associated with chronic corticosteroid use), it should be seen as a valuable tool in the rheumatologist's arsenal.