Baseline medication use is associated with Covid-19 severity in people with rheumatic diseases

Priscilla Lynch provides a round-up of some of the most topical research presented at this year’s EULAR Congress, which took place virtually from 2-5 June

Two abstracts presented at EULAR 2021 show people taking rituximab or Janus kinase inhibitors (JAKi) have worse Covid-19 severity compared to people taking tumour necrosis factor inhibitors (TNFi). These data from two large registry initiatives highlight the urgent need for strategies to manage the risk in people taking antirheumatic drugs, such as identifying optimal timing for vaccination.

This analysis from Jeffrey Sparks, Zachary Wallace, and colleagues aimed to investigate the associations between baseline use of biologic or targeted synthetic DMARDs with a range of poor Covid-19 outcomes specifically in people with rheumatoid arthritis (RA). The treatments included were abatacept, rituximab, JAKi, interleukin-6 inhibitors (IL-6i), or TNFi. Of 1,673 people with RA taking b/tsDMARDs when they developed Covid-19, 498 (34.3 per cent) were hospitalised and 112 (6.7 per cent) died.

People who developed severe Covid-19 had received rituximab infusion more recently compared to people with mild or moderate infection

Rituximab users were more likely than TNFi users to have interstitial lung disease (ILD; 11.6 per cent versus 1.7 per cent) and history of cancer (7.1 per cent vs 2.0 per cent); while JAKi users were more likely than TNFi users to be obese (17.3 per cent versus 9.0 per cent). After propensity score matching, the authors found that rituximab was strongly associated with greater odds of having a worse Covid-19 outcome compared to TNFi. Among rituximab users, 42 (18.8 per cent) died compared to 27 (3.3 per cent) of TNFi users.

JAKi use was also associated with greater odds of having a worse Covid-19 severity. People taking abatacept or IL-6i did not have worse Covid-19 severity compared to TNFi. Overall, the results were similar in the sensitivity analysis and after excluding cancer or ILD. Similar results regarding rituximab have been found in the French RMD cohort.
Avouac and colleagues reported findings on behalf of a consortium of contributors, including FAI2R, SFR, SNFMI, SOFREMIP, CRI, and IMIDIATE. Of 1,090 people included with rheumatic diseases – mainly RA – 137 developed severe Covid-19 disease (12.6 per cent).

After adjusting for potential confounding factors, severe disease was confirmed to be more frequent in patients receiving rituximab. People who developed severe Covid-19 had received rituximab infusion more recently compared to people with mild or moderate infection. In this cohort, 89 people died – an overall death rate of 8.2 per cent. The death rate was numerically higher in people receiving rituximab (20.6 per cent) compared to those not (7.4 per cent), and the subgroup of untreated patients with diseases eligible for rituximab therapy (9.9 per cent).

However, after adjusting for confounding factors, the risk of death was not significantly increased in people treated with rituximab, although the length of hospital stay was markedly longer in people treated with rituximab compared to both untreated groups. Results so far from these registries of people with RA and Covid-19 show that baseline use of rituximab or JAKi is associated with worse severity of Covid-19 compared to TNFi use.

The elevated odds for poor Covid-19 outcomes in people taking rituximab highlights the urgent need for strategies to limit their risk, such as optimal vaccination timing. The global alliance finding that JAKi are associated with poor Covid-19 outcomes is novel, and needs to be reproduced in other studies.