Objective

Dermatomyositis (DM) and polymyositis (PM) are debilitating inflammatory myopathies associated with significant mortality. We evaluated the relative contribution of infection to hospital mortality in a large population-based study of individuals with PM/DM.

Methods

Data derive from the 2007 to 2011 Healthcare Cost and Utilization Project National Inpatient Samples and include all hospital discharges that met a validated administrative definition of PM/DM. The primary outcome was hospital mortality. Variables for infections and comorbidities were generated from discharge diagnoses using validated administrative definitions. Logistic regression was used to investigate the relationship between infection and mortality in individuals with PM/DM, adjusting for sociodemographics, utilization variables, and comorbidities. Relative risks (RRs) were calculated to compare the overall prevalence of specific infections and associated mortality in PM/DM hospitalizations with those seen in the general hospitalized population.

Results

A total of 15,407 hospitalizations with PM/DM met inclusion criteria for this study and inpatient mortality was 4.5% (700 deaths). In adjusted logistic regression analyses, infection (odds ratio [OR] 3.4, 95% confidence interval [95% CI] 2.9-4.0) was the strongest predictor of hospital mortality among individuals with PM/DM. Bacterial infection (OR 3.5, 95% CI 3.0-4.1), comprised primarily of pneumonia and bacteremia, and opportunistic fungal infections (OR 2.5, 95% CI 1.5-4.0) were independently associated with hospital mortality. The overall burden of infection in hospitalizations with PM/DM was significantly increased in comparison with the general hospitalized population (RR 1.5, 95% CI 1.4-1.6).

Conclusion

Among hospitalized individuals with PM/DM, infection is the leading cause of mortality. Strategies to mitigate infection risk in both the clinic and hospital settings should be evaluated to improve disease outcomes.

The limited effectiveness of rituximab plus intravenous immunoglobulin (IVIG) in desensitization may be due to incomplete B cell depletion. Obinutuzumab is a type 2 anti-CD20 antibody that induces increased B cell depletion relative to rituximab and may therefore be more effective for desensitization. This open-label phase 1b study assessed the safety, pharmacokinetics, and pharmacodynamics of obinutuzumab in highly sensitized patients with end-stage renal disease. Patients received 1 (day 1, n = 5) or 2 (days 1 and 15; n = 20) infusions of 1000-mg obinutuzumab followed by 2 doses of IVIG on days 22 and 43. Eleven patients received additional obinutuzumab doses at the time of transplant and/or at week 24. The median follow-up duration was 9.4 months. Obinutuzumab was well tolerated, and most adverse events were grade 1-2 in severity. There were 11 serious adverse events (SAEs) in 9 patients (36%); 10 of these SAEs were infections and 4 occurred after kidney transplant. Obinutuzumab plus IVIG resulted in profound peripheral B cell depletion and appeared to reduce B cells in retroperitoneal lymph nodes. Reductions in anti-HLA antibodies, number of unacceptable antigens, and the calculated panel reactive antibody score as centrally assessed using single-antigen bead assay were limited and not clinically meaningful for most patients (NCT02586051).