Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry

Abstract

Objectives: To determine factors associated with COVID-19-related death in people with rheumatic diseases.

Methods: Physician-reported registry of adults with rheumatic disease and confirmed or presumptive COVID-19 (from 24 March to 1 July 2020). The primary outcome was COVID-19-related death. Age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications were included as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category.

Results: Of 3729 patients (mean age 57 years, 68% female), 390 (10.5%) died. Independent factors associated with COVID-19-related death were age (66-75 years: OR 3.00, 95% CI 2.13 to 4.22; >75 years: 6.18, 4.47 to 8.53; both vs ≤65 years), male sex (1.46, 1.11 to 1.91), hypertension combined with cardiovascular disease (1.89, 1.31 to 2.73), chronic lung disease (1.68, 1.26 to 2.25) and prednisolone-equivalent dosage >10 mg/day (1.69, 1.18 to 2.41; vs no glucocorticoid intake). Moderate/high disease activity (vs remission/low disease activity) was associated with higher odds of death (1.87, 1.27 to 2.77). Rituximab (4.04, 2.32 to 7.03), sulfasalazine (3.60, 1.66 to 7.78), immunosuppressants (azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus: 2.22, 1.43 to 3.46) and not receiving any disease-modifying anti-rheumatic drug (DMARD) (2.11, 1.48 to 3.01) were associated with higher odds of death, compared with methotrexate monotherapy. Other synthetic/biological DMARDs were not associated with COVID-19-related death.

Conclusion: Among people with rheumatic disease, COVID-19-related death was associated with known general factors (older age, male sex and specific comorbidities) and disease-specific factors (disease activity and specific medications). The association with moderate/high disease activity highlights the importance of adequate disease control with DMARDs, preferably without increasing glucocorticoid dosages. Caution may be required with rituximab, sulfasalazine and some immunosuppressants.

Keywords: antirheumatic agents; autoimmune diseases; epidemiology; glucocorticoids; health care; outcome assessment.

Figure 1

Disease and medication groups. ANCA, anti-neutrophil cytoplasm antibodies; DMARD, disease-modifying antirheumatic drugs; IgG, immunoglobulin; IL, interleukin; JAK, Janus kinase; TNF, tumour necrosis factor.

Figure 2

Patient flowchart. Some patients had diagnoses in multiple groups; as a result, the sum of patients in each group is greater than the total number of patients. (*) Patients belonging to more than one diagnosic group: IJD and CTD: N=78 (10 deaths); IJD and other: N=70 (12 deaths); CTD and other: N=50 (13 deaths); IJD and CTD and other: N=5 (2 deaths). (§) Patients belonging to more than one diagnosic group: IJD and CTD: N=77 (10 deaths); IJD and other: N=70 (12 deaths); CTD and other: N=49 (12 deaths); IJD and CTD and other: N=5 (2 deaths). (#) Patients belonging to more than one diagnosic group: IJD and CTD: N=59 (7 deaths). (**) Non-typical DMARDs for IJD and RA: immunosuppressants and belimumab; non-typical DMARDs for RA: IL-17/IL-23/IL-12+23 inhibitors. (***) Non-typical DMARDs for CTD: abatacept, IL-17/IL-23/IL-12+23 inhibitors, sulfasalazine, leflunomide and tsDMARDs. b/tsDMARDs, biological/targeted synthetic disease-modifying antirheumatic drugs; CTD, connective tissue disease/vasculitis; DMARDs, disease-modifying anti-rheumatic drugs; IJD, inflammatory joint disease; IL, interleukin; RA, rheumatoid arthritis.

Figure 3

Results of the main logistic regression analysis. Shown are multivariable-adjusted ORs for the outcome COVID-19-related death with 95% CIs, assessing the association with (A) general patient characteristics, (B) comorbidities, (C) rheumatic disease diagnoses (RMD) and (D) rheumatic disease medications. ORs are shown for four groups: all patients (black), patients with inflammatory joint disease (red), patients with rheumatoid arthritis (orange), and patients with a connective tissue disease or vasculitis (blue). For (C), only ORs for all patients are shown. The reference categories are as follows: (A) ≤65 years, females, never smoked, remission or low disease activity; (B) the non-presence of the specific comorbidities (for all effects); (C) rheumatoid arthritis (for all effects); (D) methotrexate monotherapy (for all effects except for glucocorticoids), no glucocorticoids (for glucocorticoid dosage groups). Patients receiving multiple csDMARDs or immunosuppressants (except glucocorticoids) were grouped according to the following hierarchy: immunosuppressants>sulfasalazine>antimalarials>leflunomide>methotrexate; patients receiving a b/tsDMARD were considered solely in the b/tsDMARD group; glucocorticoids were examined separately and categorised by prednisolone-equivalent dosage (1–10 mg/day and >10 mg/day). bDMARD, biological disease-modifying anti-rheumatic drug; csDMARD, conventional synthetic disease-modifying antirheumatic drug; CTD, connective tissue diseases; CVD, cardiovascular disease; JIA, juvenile idiopathic arthritis; tsDMARD, targeted synthetic disease-modifying anti-rheumatic drug.