Dataset Information

Rituximab and abatacept but not tocilizumab impair antibody response to pneumococcal conjugate vaccine in patients with rheumatoid arthritis.

ABSTRACT: The 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).Patients 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.In 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%.In 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.NCT00828997 and EudraCT EU 2007-006539-29.

SUBMITTER: Crnkic Kapetanovic M

PROVIDER: S-EPMC3978887 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Rituximab and abatacept but not tocilizumab impair antibody response to pneumococcal conjugate vaccine in patients with rheumatoid arthritis.

Crnkic Kapetanovic Meliha M Saxne Tore T Jönsson Göran G Truedsson Lennart L Geborek Pierre P

Arthritis research & therapy 20131030 5

<h4>Introduction</h4>The 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).<h4>Methods</h4>Patients 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 ...[more]

PMID: 24286269

Similar Datasets

Project description:BackgroundPatients with rheumatoid arthritis (RA), including those treated with biologics, are at increased risk of some vaccine-preventable infections. We evaluated the antibody response to standard 23-valent pneumococcal polysaccharide vaccine (PPSV23) and the 2011-2012 trivalent seasonal influenza vaccine in adults with RA receiving subcutaneous (SC) abatacept and background disease-modifying anti-rheumatic drugs (DMARDs).MethodsTwo multicenter, open-label sub-studies enrolled patients from the ACQUIRE (pneumococcal and influenza) and ATTUNE (pneumococcal) studies at any point during their SC abatacept treatment cycle following completion of ≥3 months' SC abatacept. All patients received fixed-dose abatacept 125 mg/week with background DMARDs. A pre-vaccination blood sample was taken, and after 28 ± 3 days a final post-vaccination sample was collected. The primary endpoint was the proportion of patients achieving an immunologic response to the vaccine at Day 28 among patients without a protective antibody level to the vaccine antigens at baseline (pneumococcal: defined as ≥2-fold increase in post-vaccination titers to ≥3 of 5 antigens and protective antibody level of ≥1.6 μg/mL to ≥3 of 5 antigens; influenza: defined as ≥4-fold increase in post-vaccination titers to ≥2 of 3 antigens and protective antibody level of ≥1:40 to ≥2 of 3 antigens). Safety and tolerability were evaluated throughout the sub-studies.ResultsPre- and post-vaccination titers were available for 113/125 and 186/191 enrolled patients receiving the PPSV23 and influenza vaccine, respectively. Among vaccinated patients, 47/113 pneumococcal and 121/186 influenza patients were without protective antibody levels at baseline. Among patients with available data, 73.9 % (34/46) and 61.3 % (73/119) met the primary endpoint and achieved an immunologic response to PPSV23 or influenza vaccine, respectively. In patients with pre- and post-vaccination data available, 83.9 % in the pneumococcal study demonstrated protective antibody levels with PPSV23 (titer ≥1.6 μg/mL to ≥3 of 5 antigens), and 81.2 % in the influenza study achieved protective antibody levels (titer ≥1:40 to ≥2 of 3 antigens) at Day 28 post-vaccination. Vaccines were well tolerated with SC abatacept with background DMARDs.ConclusionsIn these sub-studies, patients with RA receiving SC abatacept and background DMARDs were able to mount an appropriate immune response to pneumococcal and influenza vaccines.Trial registrationNCT00559585 (registered 15 November 2007) and NCT00663702 (registered 18 April 2008).

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: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:BackgroundPneumococcal vaccination is recommended to patients with rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS). However, little is known whether the diseases influence pneumococcal vaccine response. This study aimed to investigate antibody response and functionality of antibodies following immunization with 13-valent pneumococcal conjugate vaccine (PCV13) in RA patients or pSS patients without disease modifying anti-rheumatic drugs (DMARD), compared to patients with RA treated with DMARD or to healthy controls.MethodsSixty RA patients (50 without DMARD and 10 with MTX), 15 patients with pSS and 49 controls received one dose of PCV13. Serotype-specific antibody concentrations for pneumococcal polysaccharides 6B and 23F and functionality of antibodies (23F) were determined in serum taken before and 4-6 weeks after vaccination using ELISA and opsonophagocytic activity assay (OPA), respectively. Proportions of individuals with positive antibody response (i.e. ≥ 2-fold increase from prevaccination concentrations; antibody response ratio; ARR ≥ 2), percentage of individuals reaching putative protective antibody level (i.e. ≥1.3 μg/mL) for both serotypes, and difference in OPA were calculated.ResultsAfter vaccination, antibody concentrations for both serotypes increased in RA without DMARD (p < 0.001), pSS (p ≤ 0.05 and < 0.01) and controls (p < 0.001). Antibody responses to 6B and 23F were comparable in RA without DMARD (64% and 74%), pSS (67% and 53%) and controls (65% and 67%), but lower in the small group RA with MTX (both 20%, p < 0.01). Similarly, significant increases of patients reaching protective antibody levels were seen in RA without DMARD (p ≤ 0.001) and controls (p < 0.001). After vaccination, OPA increased significantly in controls, RA and pSS without DMARD (p < 0.001 to 0.03), but not in RA with MTX.ConclusionsPneumococcal conjugate vaccine is immunogenic in RA and pSS patients without DMARD and in line with previous studies we support the recommendation that vaccination of RA patients should be performed before the initiation of MTX.Trial registrationClinicalTrials.gov Identifier: NCT02240888. Retrospectively registered 4 September, 2014.

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.

Dataset Information

Rituximab and abatacept but not tocilizumab impair antibody response to pneumococcal conjugate vaccine in patients with rheumatoid arthritis.

Publications

Rituximab and abatacept but not tocilizumab impair antibody response to pneumococcal conjugate vaccine in patients with rheumatoid arthritis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets