Does tnf-inhibition decrease the risk of severe COVID-19 in rmd-patients

Hasseli, R.; Hoyer, B. F.; Krause, A.; Lorenz, H. M.; Pfeil, A.; Regierer, A.; Richter, J.; Schmeiser, T.; Strangfeld, A.; Schulze-Koops, H.; Voll, R.; Specker, C.; Müller-Ladner, U.

Background: Patients with rheumatic and musculoskeletal diseases (RMD) might have an increased risk for infection due to their immunomodulatory treatment, secondary to their disease and comorbidities. Recent studies suggest a decreased risk of severe COVID-19 in RMD-patients treated with biologics. Objectives: The aim of this study was to assess courses of RMD patients treated with TNF-inhibitors (TNF-I) included in the German COVID-19 registry. Methods: In the German physician-reported COVID-19-RMD registry, patients with an RMD and confirmed SARS-CoV-2-infection were documented (data entered between March 30, 2020 and January 30, 2021). We analysed TNF-I treated patients, their course and outcome of the infection. Data were compared to RMD-patients treated with other immunomodulatory drugs (OID) than TNF-I. Results: A total of 269 patients were treated with a TNF-I (57% female) compared to 874 patients who were treated with OID (68% female). Median age was 52 years (range: 19-87) in the TNF-I-group versus 58 years (range: 18-91) in the OID-group. Rheumatoid arthritis was the most common diagnosis (38% in TNF-I-group vs. 52% in the OID-group), followed by ankylosing spondylitis (32% vs. 6%), psoriatic arthritis (22% vs. 11%) and other RMD (9% vs. 31%). Adalimumab (35%) and etanercept (35%) were the most frequently used TNF-I (tab. 1). Glucocorticoids (GC) were used in 22% of TNF-I-treated patients and in 42% of the OID-group. Under TNF-I, stable disease was reported prior to the SARS-CoV-2-infection in 53% of the patients (OID-group: 47%), followed by low disease activity in 35% (OID: 34%), moderate disease activity in 6% (OID: 12%) and high disease activity in 4% (OID: 3%). Most frequent comorbidities were arterial hypertension (29% under TNF-I vs. 35% under OID), diabetes (8% vs. 11%) and cardiovascular diseases (7% vs. 12%). The most common reported COVID-19 symptoms were dry cough (57% vs. 55%), fever (53% vs. 61%) and fatigue (50% vs. 49%). Hospitalization due to SARSCoV infection was required in only 12% of the TNF-I-treated cases vs. in 29% in the OID-group. Oxygen treatment was necessary in 5% of the patients under TNF-I compared to 22% under OID and invasive ventilation in 2% in the TNF-Igroup compared to 6% under OID. Most notably, no fatal courses of COVID-19 were reported among the 269 RMD-patients treated with TNF-I versus 49 deaths in the 874 cases (5.6%) treated with OID. Focussing on the hospitalizated TNF-I patients, the rate of concomitant GC use (p<0.001) and higher disease activity (p=0.005) was significant higher (tab.1). Conclusion: High or moderate RMD-disease activity is an important factor associated with severity of COVID-19 including mortality. In this large cohort RMD patients treated with TNF-I show a low hospitalisation rate and no fatal course. This is reassuring for patients and treating rheumatologists to use TNF-I to control RMD disease activity. The use of glucocorticoids and high disease activity seem to counteract possible protective effects of TNF-I.