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Current perspective on rituximab in rheumatic diseases.

ABSTRACT: The steadily increasing knowledge regarding pathogenetic mechanisms in autoimmune rheumatic diseases has paved the way to different therapeutic approaches. In particular, the market entry of biologics has dramatically modified the natural history of rheumatic chronic inflammatory diseases with a meaningful impact on patients' quality of life. Among the wide spectrum of available biological treatments, rituximab (RTX), first used in the treatment of non-Hodgkin's lymphoma, was later approved for rheumatoid arthritis and anti-neutrophil cytoplasmic antibodies-associated vasculitis. Nowadays, in rheumatology, RTX is also used with off-label indications in patients with systemic sclerosis, Sjögren's syndrome and systemic lupus erythematosus. RTX is a monoclonal antibody directed to CD20 molecules expressed on the surfaces of pre-B and mature B lymphocytes. It acts by causing apoptosis of these cells with antibody- and complement-dependent cytotoxicity. As inflammatory responses to cell-associated immune complexes are key elements in the pathogenesis of several autoimmune rheumatic diseases, such an approach might be effective in these patients. In fact, RTX, by promoting the rapid and long-term depletion of circulating and lymphoid tissue-associated B cells, leads to a lower recruitment of these effector cells at sites of immune complex deposition, thus reducing inflammation and tissue damage. RTX is of the most interest to rheumatologists as it represents an important additional therapeutic approach. Thus, the advent in clinical practice of approved RTX biosimilars, such as CT-P10, may be of help in improving treatment access as well as in reducing costs.

SUBMITTER: Schioppo T

PROVIDER: S-EPMC5633295 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Current perspective on rituximab in rheumatic diseases.

Schioppo Tommaso T Ingegnoli Francesca F

Drug design, development and therapy 20171003

The steadily increasing knowledge regarding pathogenetic mechanisms in autoimmune rheumatic diseases has paved the way to different therapeutic approaches. In particular, the market entry of biologics has dramatically modified the natural history of rheumatic chronic inflammatory diseases with a meaningful impact on patients' quality of life. Among the wide spectrum of available biological treatments, rituximab (RTX), first used in the treatment of non-Hodgkin's lymphoma, was later approved for ...[more]

PMID: 29042750

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Project description:BackgroundVarious observations have suggested that the course of COVID-19 might be less favourable in patients with inflammatory rheumatic and musculoskeletal diseases receiving rituximab compared with those not receiving rituximab. We aimed to investigate whether treatment with rituximab is associated with severe COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases.MethodsIn this cohort study, we analysed data from the French RMD COVID-19 cohort, which included patients aged 18 years or older with inflammatory rheumatic and musculoskeletal diseases and highly suspected or confirmed COVID-19. The primary endpoint was the severity of COVID-19 in patients treated with rituximab (rituximab group) compared with patients who did not receive rituximab (no rituximab group). Severe disease was defined as that requiring admission to an intensive care unit or leading to death. Secondary objectives were to analyse deaths and duration of hospital stay. The inverse probability of treatment weighting propensity score method was used to adjust for potential confounding factors (age, sex, arterial hypertension, diabetes, smoking status, body-mass index, interstitial lung disease, cardiovascular diseases, cancer, corticosteroid use, chronic renal failure, and the underlying disease [rheumatoid arthritis vs others]). Odds ratios and hazard ratios and their 95% CIs were calculated as effect size, by dividing the two population mean differences by their SD. This study is registered with ClinicalTrials.gov, NCT04353609.FindingsBetween April 15, 2020, and Nov 20, 2020, data were collected for 1090 patients (mean age 55·2 years [SD 16·4]); 734 (67%) were female and 356 (33%) were male. Of the 1090 patients, 137 (13%) developed severe COVID-19 and 89 (8%) died. After adjusting for potential confounding factors, severe disease was observed more frequently (effect size 3·26, 95% CI 1·66-6·40, p=0·0006) and the duration of hospital stay was markedly longer (0·62, 0·46-0·85, p=0·0024) in the 63 patients in the rituximab group than in the 1027 patients in the no rituximab group. 13 (21%) of 63 patients in the rituximab group died compared with 76 (7%) of 1027 patients in the no rituximab group, but the adjusted risk of death was not significantly increased in the rituximab group (effect size 1·32, 95% CI 0·55-3·19, p=0·53).InterpretationRituximab therapy is associated with more severe COVID-19. Rituximab will have to be prescribed with particular caution in patients with inflammatory rheumatic and musculoskeletal diseases.FundingNone.

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Current perspective on rituximab in rheumatic diseases.

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Current perspective on rituximab in rheumatic diseases.

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