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Abatacept and tocilizumab tapering in rheumatoid arthritis patients: results of SONATA-a retrospective, exploratory cohort study.

ABSTRACT: Objectives:As data on disease-activity-guided dose optimization of abatacept and tocilizumab are scarce, we explored the feasibility, effectiveness and safety of dose optimization of these biological DMARDs in RA patients in daily practice. Methods:RA patients who had been treated with abatacept or tocilizumab for ?6 months, with DAS28?<3.2, were included. Four groups were identified: abatacept dose reduction (DR) and usual care (UC), and tocilizumab DR and UC. Successful DR and discontinuation entailed being on a lower dose than at baseline or having discontinued abatacept or tocilizumab, while maintaining disease activity score with ESR using 28 joint count (DAS28)?<3.2. Proportions of patients with successful DR or discontinuation at 12 months were described. Maintenance of DR was investigated using Kaplan-Meier curves. Between-group differences in mean DAS28 and Health assessment questionnaire disability index (HAQ-DI) change (?) over 6 and 12 months were estimated. Results:One hundred and nineteen patients were included. DR was attempted in 13 of 28 (46%; 95% CI: 28, 66%) abatacept and 64 of 91 (70%; 95% CI: 60, 79%) tocilizumab patients. At 12 months, 3 of 11 (27%; 95% CI: 6, 61%) abatacept and 20 of 48 (42%; 95% CI: 28, 57%) tocilizumab patients were successfully tapered. One of 11 (9%; 95% CI: 0, 41%) abatacept and 5 of 48 (10%; 95% CI: 3, 23%) tocilizumab patients were successfully discontinued. Mean ?DAS28 and ?HAQ-DI at months 6 and 12 were not significantly different between DR and UC. For tocilizumab, DAS28 was significantly higher in the DR compared with the UC group at 6 months. Adverse events were comparable between groups. Conclusion:Abatacept and tocilizumab DR appears to be feasible and safe in clinical practice. No benefits in terms of fewer adverse events in the DR group were observed. Furthermore, DR was suboptimal, because all patients were eligible for DR, but in a substantial number of patients no DR was attempted.

SUBMITTER: Bouman CAM

PROVIDER: S-EPMC6649917 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Abatacept and tocilizumab tapering in rheumatoid arthritis patients: results of SONATA-a retrospective, exploratory cohort study.

Bouman Chantal A M CAM Tweehuysen Lieke L Haverkort Dieneke D van den Ende Cornelia H CH van der Maas Aatke A den Broeder Alfons A AA

Rheumatology advances in practice 20180412 1

<h4>Objectives</h4>As data on disease-activity-guided dose optimization of abatacept and tocilizumab are scarce, we explored the feasibility, effectiveness and safety of dose optimization of these biological DMARDs in RA patients in daily practice.<h4>Methods</h4>RA patients who had been treated with abatacept or tocilizumab for ≥6 months, with DAS28 <3.2, were included. Four groups were identified: abatacept dose reduction (DR) and usual care (UC), and tocilizumab DR and UC. Successful DR and d ...[more]

PMID: 31431957

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Project description:OBJECTIVE:To compare the effectiveness and safety of three non-tumour necrosis factor (TNF) ? inhibitors (rituximab, abatacept, and tocilizumab) in the treatment of rheumatoid arthritis. DESIGN:Population based prospective study. SETTING:53 university and 54 non-university clinical centres in France. PARTICIPANTS:3162 adults (>18 years) with rheumatoid arthritis according to 1987 American College of Rheumatology criteria, enrolled in one of the three French Society of Rheumatology registries; who had no severe cardiovascular disease, active or severe infections, or severe immunodeficiency, with follow-up of at least 24 months. INTERVENTION:Initiation of intravenous rituximab, abatacept, or tocilizumab for rheumatoid arthritis. MAIN OUTCOME MEASURE:The primary outcome was drug retention without failure at 24 months. Failure was defined as all cause death; discontinuation of rituximab, abatacept, or tocilizumab; initiation of a new biologic or a combination of conventional disease modifying antirheumatic drugs; or increase in corticosteroid dose >10 mg/d compared with baseline at two successive visits. Because of non-proportional hazards, treatment effects are presented as life expectancy difference without failure (LEDwf), which measures the difference between average duration of survival without failure. RESULTS:Average durations of survival without failure were 19.8 months for rituximab, 15.6 months for abatacept, and 19.1 months for tocilizumab. Average durations were greater with rituximab (LEDwf 4.1, 95% confidence interval 3.1 to 5.2) and tocilizumab (3.5, 2.1 to 5.0) than with abatacept, and uncertainty about tocilizumab compared with rituximab was substantial (-0.7, -1.9 to 0.5). No evidence was found of difference between treatments for mean duration of survival without death, presence of cancer or serious infections, or major adverse cardiovascular events. CONCLUSION:Among adults with refractory rheumatoid arthritis followed-up in routine practice, rituximab and tocilizumab were associated with greater improvements in outcomes at two years compared with abatacept.

Project description:IntroductionThe objective of the study was to investigate the impact of newer biologic treatments including rituximab, abatacept and tocilizumab on antibody response following pneumococcal vaccination using a 7-valent conjugate vaccine in patients with established rheumatoid arthritis (RA).MethodsPatients with RA receiving rituximab, abatacept or tocilizumab as monotherapy or combined with methotrexate (MTX) participated in the study. Specific IgG antibodies against 23F and 6B serotypes were measured at vaccination and 4 to 6 weeks after vaccination using standardised ELISA. Geometric mean antibody levels (GML) were calculated. Antibody response (AR) was defined as the ratio between post- and pre-vaccination antibody levels and a positive antibody response (posAR) was AR ≥ 2.ResultsIn total, 88 patients were enrolled in the study. Of 55 patients treated with rituximab, 26 (46%) were on concomitant MTX. Of patients receiving abatacept (n = 17) and tocilizumab (n = 16) biologic treatment was given in combination with MTX in 13 (76%) and 9 (56%) patients, respectively. Patients treated with rituximab had significantly lower AR compared to those on tocilizumab, as well as compared to previously reported RA patients on MTX and controls (spondylarthropathy patients treated with NSAIDs and/or analgesics). In total, 10.3% of patients on rituximab monotherapy and no patient on rituximab + MTX had posAR for both serotypes. For abatacept and tocilizumab the corresponding figures were 17.6% and 50%.ConclusionIn this cohort of patients with established RA, treatment with rituximab and abatacept was associated with diminished antibody response but this was most pronounced for rituximab. Pneumococcal conjugate vaccine administrated during ongoing tocilizumab treatment seems to be associated with sufficient antibody response. Pneumococcal vaccination should preferably be encouraged before initiation of rituximab or abatacept treatment.Trial registrationNCT00828997 and EudraCT EU 2007-006539-29.

Project description:ObjectivesThe objective of this study was to evaluate the cost-effectiveness of abatacept, tocilizumab, and tumor necrosis factor (TNF) inhibitors as compared with rituximab in Finnish rheumatoid arthritis patients, who have previously been treated with TNF inhibitors.MethodsA patient-level simulation model was developed to predict costs and outcomes associated with four biological drugs (abatacept, tocilizumab, rituximab and TNF inhibitors) in the treatment of rheumatoid arthritis. Following lack of efficacy or adverse events, the patients were switched to another biological drug until all four options were exhausted. After that, the patients were assumed to receive a 6th line treatment until death. The patients' baseline characteristics and regression models used in the simulation were based on observational data from the National Register for Biological Treatments in Finland. Direct costs comprised drug costs, administration costs, costs of switching, and outpatient and inpatient care, while indirect costs included disability pension and sick leaves due to rheumatoid arthritis. Several subgroup and deterministic sensitivity analyses were conducted.ResultsDrug costs were the lowest for rituximab, but when administration costs and costs of switching were included, drug costs were the lowest for TNF inhibitors. Abatacept was associated with the highest drug costs, whereas rituximab was associated with the highest healthcare costs. In total, TNF inhibitors had the lowest direct costs, while rituximab had the highest direct costs. The amount of quality-adjusted life years (QALY) gained ranged from 9.405 for rituximab to 9.661 for TNF inhibitors. TNF inhibitors, abatacept, and tocilizumab were dominant in comparison to RTX.ConclusionsTNF inhibitors, abatacept, and tocilizumab had lower costs and higher QALYs than rituximab, and therefore, they were dominant in comparison to rituximab. As TNF inhibitors had the lowest costs and highest QALYs, they were the most cost-effective treatment option.

Project description:BackgroundWe sought to identify immunoglobin G autoantibodies predictive of early treatment response to methotrexate, the recommended first-line therapy for patients with newly diagnosed rheumatoid arthritis, and to the interleukin-6 receptor inhibitor biologic tocilizumab, initiated as the first disease-modifying anti-rheumatic drug.Materials and methodsIn baseline sera of a subset of patients with newly diagnosed rheumatoid arthritis in the U-Act-Early study, selected based on specific responder/non-responder criteria using the Disease Activity Score assessing 28 joints (DAS28) within the first 20 weeks, we measured immunoglobin G antibody reactivity against 463 protein antigens and performed supervised cluster analysis to identify predictive autoantibodies for treatment response. The analysis subset comprised 56 patients in the methotrexate arm (22 responders, 34 non-responders) and 50 patients in the tocilizumab arm (34 responders, 16 non-responders). For comparison, these analyses were also performed in 50 age- and gender-matched healthy controls.ResultsIncreased reactivity in responders versus non-responders was found in the methotrexate arm against two antigens-DOT1-like histone lysine methyltransferase (p = 0.009) and tropomyosin (p = 0.003)-and in the tocilizumab arm against one antigen-neuro-oncological ventral antigen 2 (p = 0.039). Decreased reactivity was detected against two antigens in the methotrexate arm-G1 to S phase transition 2 (p = 0.023) and the zinc finger protein ZPR1 (p = 0.021). Reactivity against the identified antigens was not statistically significant in either treatment arm for patients with rheumatoid factor-positive versus-negative or anti-cyclic citrullinated test-positive versus test-negative rheumatoid arthritis (p ≥ 0.06).ConclusionsComprehensive profiling of baseline sera revealed several novel immunoglobin G autoantibodies associated with early treatment response to methotrexate and to tocilizumab in disease-modifying anti-rheumatic drug-naive patients with rheumatoid arthritis. These findings could eventually yield clinically relevant predictive markers, if corroborated in different patient cohorts, and may facilitate future benefit in personalised healthcare.

Project description:Rheumatoid arthritis (RA) is a chronic, inflammatory disease affecting synovial joints. Patients with persistent, active disease have traditionally been treated with disease-modifying antirheumatic drugs (DMARDs) (eg, methotrexate) or biologic agents (eg, tumor necrosis factor [TNF] antagonists). However, patients may discontinue these treatments due to toxicity, infection, or lack of efficacy. Two additional biologic therapies-rituximab and abatacept-are currently available for TNF-antagonist inadequate responders. Abatacept is also indicated for inadequate responders to traditional DMARDs.The aims of this review was to provide an overview of the issues surrounding the treatment of RA patients experiencing inadequate responses to current treatment and to discuss the current and future impact of abatacept on the RA treatment armamentarium.The MEDLINE, EMBASE, and BIOSIS databases were searched (search dates: January 1, 2000-September 19, 2007) using the terms abatacept or CTLA-4 or Orencia with rheumatoid arthritis. Full text articles in English were selected for relevance, and only articles presenting primary clinical trial data from randomized, placebo-controlled, clinical trials of abatacept were included. This review focused on the Phase III trials of abatacept in methotrexate and/or TNF-antagonist inadequate responders, as these trials had the largest number of patients and the longest study durations.The literature search initially yielded 848 papers. A total of 12 articles fulfilled the inclusion criteria. Abatacept is a novel agent that has been reported to reduce the signs and symptoms of RA in patients with active RA with an inadequate response to DMARDs and/or TNF-antagonist treatment. In both of these patient populations, treatment with abatacept was found to provide clinically meaningful health-related quality-of-life benefits, such as improvements in physical function, activity limitation, sleep, and fatigue. Abatacept was reported to have a consistent safety and tolerability profile, with a low rate (3.5%-4.2%) of discontinuation due to adverse events.The efficacy and tolerability data from Phase III clinical trials suggest that abatacept is an effective and generally well tolerated treatment option for RA patients with an inadequate response to methotrexate and/or TNF antagonists.

Project description:ImportanceConsidering the widespread and increasing use of biological immunomodulators (biological disease-modifying antirheumatic drugs [bDMARDs]) to treat chronic inflammatory conditions, and the concern that immunomodulation may alter cancer risk and progression, the limited available data on use of these therapies as used in clinical practice and cancer risks are a concern.ObjectiveTo assess the risk of incident malignant neoplasms in patients with rheumatoid arthritis (RA) treated with bDMARDs.Design, setting, and participantsThis was a national register-based prospective cohort study of the public health care system in Sweden from 2006 to 2015. Cohorts of patients with RA initiating treatment with tocilizumab (n?=?1798), abatacept (n?=?2021), and rituximab (n?=?3586), a tumor necrosis factor inhibitor (TNFi) as first-ever (n?=?10?782) or second-ever (n?=?4347) bDMARD, a biologics-naive cohort treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) (n?=?46?610), and a general population comparator cohort (n?=?107?491).ExposuresTreatment with tocilizumab, abatacept, rituximab, or TNFi.Main outcomes and measuresOutcomes included a first invasive solid or hematologic malignant neoplasm, or skin cancer. Hazard ratios were calculated using Cox-regression, adjusted for age, sex, disease and treatment characteristics, and educational level.ResultsWe identified a total of 15?129 initiations of TNFi as the first or second bDMARD, 7405 initiations of other bDMARDs, and 46?610 csDMARD users. The mean age varied from 58 to 64 years, and the proportion of female patients varied from 71% to 80%, across the 7 cohorts under study. The observed numbers of events (crude incidence per 100?000 person-years) for a first invasive solid or hematologic malignant neoplasm were 50 (959) for tocilizumab, 61 (1026) for abatacept, 141 (1074) for rituximab, 478 (978) for initiators of TNFi as first bDMARD, and 169 (917) for TNFi as second bDMARD. There were no statistically significant differences between initiators of a first or second TNFi, or other bDMARDs, and bDMARD-naive RA for any of a total of 25 drug- and outcome-specific comparisons, with 1 exception (abatacept and increased risk of squamous cell skin cancer).Conclusions and relevanceThe overall risk of cancer among patients with RA initiating TNFi as first or second bDMARD, tocilizumab, abatacept, or rituximab does not differ substantially from that of biologic drug-naive, csDMARD-treated patients with RA, although altered risks for specific cancer types, or those with longer latency, cannot be excluded.

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Abatacept and tocilizumab tapering in rheumatoid arthritis patients: results of SONATA-a retrospective, exploratory cohort study.

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Abatacept and tocilizumab tapering in rheumatoid arthritis patients: results of SONATA-a retrospective, exploratory cohort study.

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