Antibodies toward infliximab are associated with low infliximab concentration at treatment initiation and poor infliximab maintenance in rheumatic diseases

International audienceINTRODUCTION: A proportion of patients receiving infliximab have antibodies toward infliximab (ATI), which are associated with increased risk of infusion reaction and reduced response to treatment. We studied the association of infliximab concentration at treatment initiation and development of ATI as well as the association of the presence of ATI and maintenance of infliximab. METHODS: All patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA) receiving infliximab beginning in December 2005 were retrospectively followed until January 2009 or until infliximab discontinuation. Trough serum infliximab and ATI concentrations were measured at each visit. The patients were separated into two groups: ATI(pos) if ATI were detected at least once during the follow-up period and ATI(neg) otherwise. Repeated measures analysis of variance was used to study the association of infliximab concentration at treatment initiation and the development of ATI. Maintenance of infliximab in the two groups was studied by using Kaplan-Meier curves. RESULTS: We included 108 patients: 17 with RA and 91 with SpA. ATI were detected in 21 patients (19%). The median time to ATI detection after initiation of infliximab was 3.7 months (1.7 to 26.0 months). For both RA and SpA patients, trough infliximab concentration during the initiation period was significantly lower for ATI(pos) than ATI(neg) patients. RA patients showed maintenance of infliximab at a median of 19.5 months (5.0 to 31.0 months) and 12.0 months (2.0 to 24.0 months) for ATI(neg) and ATI(pos) groups, respectively (P = 0.08). SpA patients showed infliximab maintenance at a median of 16.0 months (3.0 to 34.0 months) and 9.5 months (3.0 to 39.0 months) for ATI(neg) and ATI(pos) groups, respectively (P = 0.20). Among SpA patients, those who were being treated concomitantly with methotrexate had a lower risk of developing ATI than patients not taking methotrexate (0 of 14 patients (0%) vs. 25 of 77 patients (32%); P = 0.03). CONCLUSIONS: High concentrations of infliximab during treatment initiation reduce the development of ATI, and the absence of ATI may be associated with prolonged maintenance of infliximab. Thus, trough serum infliximab concentration should be monitored early in patients with rheumatic diseases

Etude transversale de la relation concentration-effet de l'infliximab au cours des rhumatismes inflammatoires

TOURS-BU Médecine (372612103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Poor assessment of bone mineral density after a forearm fracture in women aged 50 years or older: Data from a French health insurance database

International audienc

Therapeutic Drug Monitoring of Infliximab in Spondyloarthritis: An Observational Open-Label Study

International audienceBackground: Infliximab is a chimeric monoclonal antibody that binds to human tumor necrosis factor alpha and which is approved for refractory spondyloarthritis (SpA). Individual adjustment of infliximab dosage may help to improve the therapeutic response in SpA. We investigated whether a knowledge of infliximab serum concentration modifies physician decision and improves the control of disease activity in SpA. Methods: Thirty-two patients routinely treated with infliximab were included in an observational open-label study. On visit 1 (V1), according to disease activity, a preliminary therapeutic decision was selected among 4 therapeutic options (ie, decrease, increase, maintain the dosage of infliximab, or switch over for another treatment), and a blood sample was collected to measure infliximab trough serum concentration. The final therapeutic decision, based on both disease activity and infliximab serum concentration assessed at V1, was applied at the following infusion (V2). Clinical and biological evaluations were performed at V3 and V4 and compared with those at V1. Results: The measurement of infliximab trough concentration modified the therapeutic decision for 10 patients (31%). For both patients with increased or decreased infliximab dosage at V2, median Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was similar at V3 or V4 as compared with that at V1. However, a trend for an inverse relationship between infliximab serum concentrations and BASDAI was observed. Conclusions: Knowledge of infliximab trough concentration modified the therapeutic decision for SpA patients with predominantly axial symptoms but did not improve the control of disease activity as estimated by the BASDAI

Trough Infliximab Concentrations Predict Efficacy and Sustained Control of Disease Activity in Rheumatoid Arthritis

International audienceInfliximab is a chimeric monoclonal antibody that binds to human tumor necrosis factor alpha and is approved for refractory rheumatoid arthritis. We studied the association between infliximab concentration and long-term control of disease activity in patients with rheumatoid arthritis treated on a routine basis both in cross-sectional analysis and over the long term. Trough serum infliximab concentrations were measured in patients with rheumatoid arthritis receiving infliximab infusions during the period August to October 2006. Disease activity was assessed by the Disease Activity Score for 28 Joints (DAS28) and usual biologic markers. During a 42-week follow-up period, patients were classified into two groups: those continuing with the same or lower doses of infliximab (Group A = treatment success) and those who switched to another bio-pharmaceutical or required an increase in infliximab dose (Group B = treatment failure). Treatment maintenance for Group A was analyzed by categories of infliximab concentration at baseline and compared by the log rank test. In 28 patients, C-reactive protein and infliximab concentrations were inversely related. Infliximab concentration in patients with low disease activity (DAS28 3.2 or less) was higher than in those with persistent active disease (DAS28 greater than 3.2); median values were 3.26 and 0.16 mg/L, respectively (P < 0.01). Analysis after 42 weeks showed that patients in Group A had higher infliximab concentrations at baseline than those with treatment failure (P < 0.01). In rheumatoid arthritis, infliximab concentration is predictive of sustained efficacy with the same infliximab regimen and should be considered on a routine basis

COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases treated with rituximab: a cohort study

International audienceBackground: Various 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.Methods: In 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.Findings: Between 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).Interpretation: Rituximab 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