Rituximab In RA Research Articles

Can efficacy and safety data from clinical trials of rituximab in RA be extrapolated? Insights from 1984 patients from the AIR-PR Registry.

To investigate whether the efficacy and safety data from drug-registration trials can be extrapolated to real-life RA patients receiving RTX. The 'AutoImmunity and Rituximab' (AIR-PR) registry is a French multicentre, prospective cohort of RA patients treated with RTX in a real-life setting. We compared treatment responses at 12 months and serious adverse events (AEs) between eligible and non-eligible patients, by retrieving the eligibility criteria of the three rituximab-registration trials. We determined critical eligibility criteria and modelled the benefit-risk ratio according to the number of fulfilled critical eligibility criteria. Among 1984 RA patients, only 9-12% fulfilled all eligibility criteria. Non-eligible patients had fewer EULAR responses at 12 months (40.3% vs 46.9%, P = 0.044). Critical inclusion criteria included swollen joints count ≥4, tender joints count ≥4, CRP ≥15 mg/l and RF positivity. Critical exclusion criteria were age >80 years, RA-associated systemic diseases, ACR functional class IV, DMARD other than MTX and prednisone >10 mg/day. Only 20.8% fulfilled those critical eligibility criteria. During the first year, serious AEs occurred for 182 (9.2%) patients (70.3% serious infections) and patients with ≥1 critical exclusion criterion were at higher risk (hazard ratio 3.03; 95% CI 2.25-4.06; for ≥3 criteria vs 0). The incremental risk-benefit ratio decreased with the number of unmet critical inclusion criteria and of fulfilled exclusion criteria. Few real-life RA patients were eligible for the drug-registration trials. Non-eligible patients had lower chance of response, and higher risk of serious AEs. Efficacy and safety data obtained from those trials may not be generalizable to RA patients receiving RTX in real-world clinical practice.

Humoral response to coronavirus disease-19 vaccines is dependent on dosage and timing of rituximab in patients with rheumatoid arthritis.

ObjectivesHumoral response to vaccines in RA patients treated with rituximab (RTX) in standard dosages (≥1000 mg) is decreased. Ultra-low dosages (500 or 200 mg) may have better response. Also, timing after latest RTX infusion may be an important variable. We aimed to investigate the influence of RTX dosage and timing on response to COVID-19 vaccination in RA patients.MethodsA single-centre observational study (n = 196) investigated the humoral response, measured by total Ig anti-COVID-19 assay (positive response ≥1.1), 2–6 weeks after complete COVID-19 vaccination. A multivariable logistic regression model was built to study the effect of RTX dosage and time between latest rituximab and vaccination on response, adjusting for age and methotrexate use.ResultsAfter two-dose vaccination, the response rate was significantly better for patients receiving 200 mg (n = 31, 45%) rituximab compared with 1000 mg (n = 98, 26%; odds ratio 3.07, 95% CI 1.14–8.27) and for each additional month between latest rituximab and vaccination (OR 1.67, 1.39–2.01).ConclusionBoth increased time between latest rituximab infusion and complete vaccination, and 200 mg as latest dose were associated with a better response to COVID-19 vaccination and should be considered when trying to increase vaccine response after rituximab in RA patients.Trial registrationNetherlands Trial Register, https://www.trialregister.nl/, NL9342.

THU0175 REAL-WORLD EXPERIENCE OF SWITCHING FROM ORIGINATOR TO BIOSIMILAR RITUXIMAB IN RHEUMATOID ARTHRITIS

Background:Pre-clinical and trial data confirm biosimilar rituximab (RTX-B) has equivalent physicochemical properties, function, efficacy and safety as originator (RTX-O)1,2. However, real-world data are lacking, including non-medical switch to RTX-B in patients established on RTX-O. Loss of response (LOR) has been observed following open-label switch to other biosimilars3, and it is unclear how patients who develop LOR after switching should be managed.Objectives:To describe our real-world experience of non-medical switch from RTX-O to RTX-B in RA and explore treatment strategies for patients developing LOR to RTX-B (switch back to RTX-O versus other b/tsDMARDs).Methods:We conducted a retrospective observational study of RTX-treated RA patients in Leeds from May 2002–Jan 2020. From Oct 2017, all patients on RTX-O were switched to RTX-B unless specified by treating clinician or informed consent not obtained. Demographic and clinical data were collected from electronic health records. Effectiveness was assessed by DAS28-CRP and RTX retention (using Kaplan-Meier method). Changes in treatment were based on clinician judgment.Results:944 patients with RA received ≥1 cycle of RTX in Leeds over the past 17 years. Of these, 358 required RTX re-treatment during the study period (Oct 2017–Jan 2020); 263 (73.5%) switched to RTX-B, whilst 95 (26.5%) remained on RTX-O (medical reason=46.3%; patient decision=53.7%). 256/263 patients on RTX-B with 4-month data were analysed. 201/256 (78.5%) were female, mean (SD) age 63.1 (12.4), 97.7% seropositive, 81.6% on csDMARD (62.9% methotrexate), 14.8% oral steroid, 58.6% had previous bDMARDs, and mean (SD) RTX-O cycles pre-switch was 6 (3.6). Total follow-up was 378 patient-years. Mean (SD) DAS28-CRP was 3.01 (1.17) 4 months post-last cycle RTX-O and 3.32 (1.31) post-switch to RTX-B (mean diff +0.30, 95% CI 0.004-0.60; p=0.047), with increase in VAS (+5.7, 95% CI 0.09-11.37; p=0.047), but not SJC, TJC or CRP. At last follow-up, 185/256 (72.3%) patients remained on RTX-B [median (range) RTX-B cycles 2 (1-4)]. RTX-B retention rate estimates were 79.4% and 71.3% at 12 and 18 months respectively. Following RTX-B discontinuation, 33/256 patients (12.8%) switched back to RTX-O [LOR=30 (11.7%), adverse effects (AEs)=3 (1.2%)], 13/256 (5.1%) started other b/tsDMARDs, and 25/256 (9.7%) stopped treatment (no longer indicated=7, deaths=7, loss to follow-up=6, patient choice=3, new contraindication=2). Of 46 patients with LOR/AE to RTX-B, 39 discontinued after cycle 1 (C1), 5 after C2 and 2 after C3. 31/33 patients switched back to RTX-O remained on treatment but follow-up was limited [mean (SD) 7.5 (5.2) months; 23/33 had 1 cycle only]. Compared with patients treated with other b/tsDMARDs, those switched back to RTX-O had more previous RTX-O cycles [mean (SD) 6.67 (3.28) versus 2.62 (2.10); p<0.0001]. Compared with patients who remained on RTX-B (n=185), those who discontinued for LOR/AE/death (n=53) had more previous bDMARDs (mean 1.26 vs 0.83; difference 0.43, 95% CI 0.10-0.77, p=0.01), but no differences in other clinical characteristics, treatment or B-cell numbers.Conclusion:Our real-world single-centre experience of non-medical switch from RTX-O to RTX-B in RA showed approx. three quarters of patients remained on RTX-B and maintained stable disease activity. However, apparent LOR occurred in 16%. Of >10% switched back to RTX-O, the majority remained on treatment at short-term follow-up.

Doses of rituximab for retreatment in rheumatoid arthritis: influence on maintenance and risk of serious infection.

To investigate maintenance of rituximab (RTX) in RA patients re-treated with reduced doses compared with standard dose in a real life setting. The Autoimmunity and Rituximab (AIR) registry is a nationwide prospective observational cohort investigating the long-term safety and efficacy of RTX in RA. The present study included patients from the AIR registry that have been re-treated with RTX after a first course of RTX standard dose (1000 mg × 2). Two groups were defined according to dose of RTX of the first retreatment course (i.e. second course): standard dose group and reduced dose group. Five years' maintenance and rate of serious infections of the retreatment period were compared between standard dose and reduced dose groups. Analyses used the inverse probability of treatment weighting propensity score adjusted method. Among the 1986 patients from the AIR registry, 1278 were included, 1093 (85.5%) treated with standard dose and 185 (14.5%) with reduced doses. Maintenance of RTX at 5 years in the standard and reduced groups was 55.5 and 53.8%, respectively, and did not significantly differ between groups in adjusted analyses (hazard ratio = 1.03; 95% CI: 0.81, 1.30), but the cumulative RTX dose received for retreatment [1.4 (0.6) vs 2.3 (1.0) g/year, P < 0.001] and the rate of serious infections were significantly lower in the reduced dose group (adjusted hazard ratio = 0.50; 95% CI: 0.27, 0.92; P = 0.02). Use of reduced doses of RTX for retreatment did not alter the maintenance of RTX at 5 years in RA patients, but allowed a 39% total dose reduction and a lower rate of serious infections.

Body Mass Index and response to rituximab in rheumatoid arthritis

IntroductionPrevious studies suggested that obesity could negatively affect the response to anti-TNFα agents, but data are lacking on how it affects the response to rituximab (RTX). We aimed to determine whether body mass index (BMI) is involved in the response to RTX in RA. MethodsWe retrospectively analyzed data for 114 RA patients receiving RTX. Change from baseline in DAS28, pain on a visual analog scale, erythrocyte sedimentation rate, C-reactive protein level, tender and swollen joint count was analyzed at 6 months. The primary outcome was decrease in DAS28 ≥ 1.2. Secondary outcomes were EULAR good response and remission. ResultsAt baseline, the median [interquartile range] BMI was 26.8 [23.8–31.1] kg/m2. The number of patients with normal weight, overweight and obesity was 38, 41 and 35, respectively. After 6 months, the number of RA patients with DAS28 decrease ≥ 1.2 and EULAR good response and remission was 44 (38.6%), 27 (23.7%) and 24 (21.1%), respectively. In univariate analysis, the median BMI was similar among responders and non-responders for DAS28 decrease ≥1.2 (26.9 [24.1–30.1] vs. 26.8 [23.2–31.6], P=0.78), EULAR good response (27.7 [24.3–30.7] vs. 26.7 [22.3–31.5], P=0.57) and remission (26.9 [24.1–30.8] vs. 26.8 [23.2–31.5], P=0.94). Adjusted multivariable analysis confirmed a lack of association between BMI and different responses measures to RTX. BMI was only negatively associated with decreased ΔSJC (P=0.0276) and ΔTJC (P=0.0233). ConclusionBMI did not affect the response to RTX in RA. These data could help physicians to choose biologic agents for obese RA patients.

FRI0328 Fixed versus On-Flare Retreatment with Rituximab in RA – Results from the Cererra Collaboration

BackgroundThe data on how to optimally retreat patients with RA with rituximab (RTX) have been limited so far.ObjectivesThe aim of this analysis was to compare two common retreatment strategies: A...

SAT0229 Effectiveness of Repeated Courses of Rituximab in RA – Results from the Cererra Collaboration

BackgroundRetreatment with rituximab (RTX) is common clinical practice, although several aspects regarding retreatment, such as frequency, need to be further elucidated.ObjectivesThe aim of this study was to describe the effectiveness...

AB0333 Overall response pattern of rituximab in ra-single centre experience

BackgroundCurrent approach to treatment with rituximab in RA is treat to target1. Rituximab requires repeat cycles, usually given as fixed retreatment or on clinical relapse. We have followed a retreat...

FRI0255 The 158vv fcgamma receptor 3a genotype is associated with response to rituximab in rheumatoid arthritis: results of an italian multicentre study

BackgroundReceptors for IgG allow antibody-dependent cell cytotoxicity, and the polymorphism 158V/F (rs396991) of the Fc fragment of IgG type 3A (FCG3A) was investigated as a genetic factor influencing disease response...

AB0529 Rituximab therapy monitoring by mtor, autophagy-related ULK1, caspase 3, CDK-inhibitor P21, TNF alpha, and osteoclast-specific cathepsin K and gelatinase MMP-9 gene expression in the peripheral blood of rheumatoid arthritis patients

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial hyperplasia, mononuclear cell infiltration, bone erosion and joint destruction. Altered rates of cell proliferation and apoptosis were also observed...

FRI0238 The effect of rituximab on lipid levels in patients with rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is known to be associated with cardiovascular comorbidity. In particular, patients with RA are known to be at increased for the development of atherosclerosis. Treatment with biological...

BSR and BHPR guidelines on the use of rituximab in rheumatoid arthritis

The Standards, Audit and Guidelines Working Group (SAGWG) of the British Society for Rheumatology (BSR) have recently updated the guidelines on eligibility for anti-TNF drugs in RA [1] and have updated the anti-TNF safety and efficacy guidelines [2] for general use of the rheumatology community. The National Institute for Heath and Clinical Excellence (NICE) in the UK, which is the is an independent organization responsible for providing national guidance in the UK on promoting good health and preventing and treating ill health, has published a technology appraisal guidance [3] for use of rituximab in RA in 2007. Furthermore, a consensus statement from EULAR [4] was also published in 2007. Therefore, it was felt appropriate to undertake a review of the currently available data as new evidence was available. The group did not wish to duplicate the guidance in those documents, but wished to review the more recent evidence and supplement what is already known.

CXCL13: a novel biomarker of B-cell return following rituximab treatment and synovitis in patients with rheumatoid arthritis

The B-cell chemokine, CXCL13, is a proposed serum biomarker of synovitis in RA. Its behaviour in the context of B-cell depletion therapy and reconstitution was studied during treatment of RA with rituximab. Serum samples from 20 RA patients were analysed for CXCL13, RF-IgM and anti-CCP by ELISA before and 2 and 6 months following rituximab treatment. B cells were monitored by flow cytometry. Gene expression in blood and synovial biopsies was determined by qPCR. Patients with detectable B cells at 6 months had significantly higher levels of CXCL13 and RF-IgM and slightly higher levels of anti-CCP throughout the study, including at baseline, compared with patients with undetectable B cells at 6 months. Conversely, 10 of 12 patients with high baseline CXCL13 had detectable circulating B cells at 6 months, whereas no B cells could be detected at 6 months in patients with low baseline CXCL13. Synovial CXCL13 expression at baseline correlated significantly with serum CXCL13 levels, and the synovium of patients with high serum CXCL13 expressed elevated levels of IL-1β, IL-8, MMP1 and MMP3. In addition, synovial CXCL13 expression correlated significantly with several synovial inflammatory markers. Serum CXCL13 is predictive of the rate of B-cell repopulation following a course of rituximab in RA. Serum CXCL13 correlates with synovial CXCL13 measured at a single joint, suggesting synovitis as an important source of circulating CXCL13. Within the synovium, CXCL13 expression is highly correlated with markers of synovitis. ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00147966.

Study: Use of Statins May Limit Effect of Rituximab in RA

Study: Use of Statins May Limit Effect of Rituximab in RA

Use of Statins May Limit Effect of Rituximab in RA

Use of Statins May Limit Effect of Rituximab in RA