Rate of discontinuation and drug survival of biologic therapies in rheumatoid arthritis: a systematic review and meta-analysis of drug registries and health care databases

Souto, Alejandro; Maneiro, José Ramón; Gόmez-Reino, J.J.

doi:10.1093/rheumatology/kev374

Cited by 126 publications

(163 citation statements)

References 95 publications

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“…Of note, the age did not predict discontinuation for any causes, including adverse effects or a lack of efficacy. The disease duration did however predict a higher discontinuation for adverse effects [59]. According to the Swiss (SCQM-RA) and Dutch (DREAM) cohorts the drug discontinuation rates also appear to be similar in both young, elderly [42,50] and very elderly (≥ 75 years) [42] with roughly quarter of patients stopping the treatment within the observation time.…”

Section: 12tolerability and Safetymentioning

confidence: 89%

Safety and Efficacy of Biological Disease-Modifying Antirheumatic Drugs in Older Rheumatoid Arthritis Patients: Staying the Distance

Ishchenko

Lories

2016

Drugs Aging

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The population of elderly individuals with rheumatoid arthritis is rapidly expanding, mainly due to the increased life expectancy. While targeted biological therapies are well established for the treatment of this disease, their use may be lower in elderly (> of 65 years old) and very elderly patients (> 75 years old) due to perceived higher risks for adverse events in this population taking into account comorbidity, polypharmacy and frailty. In this review we discuss available evidence for the use of biological therapies in this growing patient group with specific attention towards eventual reasons for biological treatment failure or withdrawal. The majority of data is found in secondary analyses of clinical trials and in retrospective cohorts. Most information is available about tumor necrosis factor (TNF) blockers. Older patients seem to have a less robust response to anti-TNF agents than a younger population, but drug survival that may considered a proxy for efficacy does not seem to be influenced by age. Despite an overall rate of adverse effects comparable to that in younger patients, elderly RA patients are at higher risk of serious infections. Other biologics appear to have an efficacy similar to anti-TNF agents, also in the elderly RA patients. Again, the drug survival rates for tocilizumab, rituximab and abatacept resemble those in young RA patients with good general tolerability and safety profiles. The cardiovascular risk and the risk of cancer, increased in RA patents and in the elderly patients, do not appear to be strongly influenced by biologicals. Key points-Biological drugs targeting specific cytokines or immune cell populations are an important part of the management strategy for rheumatoid arthritis patients, including the elderly. 3-Overall safety and tolerability in the elderly patients is very good and age should not be a critical factor to decide against biological drug use.-The drug survival rate of biologicals in the elderly RA patients is comparable to that in the young RA population.-Co-morbidities and risk of infection are important variables to assess when considering a biological drug in the elderly.-More data and specific studies are required to better position biological drug use in this particular population as current studies provide a low level of evidence. Data in patients above 75 years are still largely missing. Moreover, the group of elderly patients that were included in clinical trials may be influenced by selection bias at inclusion and not be fully representative for infections risks and other comorbidities.4

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Section: 12tolerability and Safetymentioning

confidence: 89%

Safety and Efficacy of Biological Disease-Modifying Antirheumatic Drugs in Older Rheumatoid Arthritis Patients: Staying the Distance

Ishchenko

Lories

2016

Drugs Aging

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“…Since their introduction in the late 1990s, multiple observational studies have compared discontinuation of TNF antagonists, but the results were inconsistent [11–15] due to methodological and clinical heterogeneity. Methodological heterogeneity, defined as “variability in study design and risk of bias” [16], may be caused, for example, by differences in data collection.…”

Section: Introductionmentioning

confidence: 99%

Heterogeneity in Comparisons of Discontinuation of Tumor Necrosis Factor Antagonists in Rheumatoid Arthritis - A Meta-Analysis

et al. 2016

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ObjectiveWe did a systematic review of studies comparing discontinuation of tumor necrosis factor alpha (TNF) antagonists in rheumatoid arthritis (RA) patients, pooled hazard ratios and assessed clinical and methodological heterogeneity.MethodsWe searched MEDLINE and EMBASE until June 2015 for pairwise hazard ratios for discontinuing infliximab, etanercept, and adalimumab from cohorts of RA patients. Hazard ratios were pooled using inverse variance weighting and random effects estimates of the combined hazard ratio were obtained. Clinical and methodological heterogeneity was assessed using the between-subgroup I-square statistics and meta-regression.ResultsTwenty-four unique studies were eligible and large heterogeneity (I-square statistics > 50%) was observed in all comparisons. Type of data, location, and order of treatment (first or second line) modified the magnitude and direction of discontinuation comparing infliximab with either adalimumab or etanercept; however, some heterogeneity remained. No effect modifier was identified when adalimumab and etanercept were compared.ConclusionHeterogeneity in studies comparing discontinuation of TNF antagonists in RA is partially explained by type of data, location, and order of treatment. Pooling hazard ratios for discontinuing TNF antagonists is inappropriate because largely unexplained heterogeneity was demonstrated when random effect estimates were calculated.

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“…Data from a meta-analysis looking at world-wide registries and other healthcare databases mimicked the large registry studies showing higher discontinuation rates for mAbs compared with ETN at 3 and 4 years yet similar rates for shorter time periods [34]. Female sex predicted higher discontinuation rates; although there was no obvious explanation for this, they did observe a higher percentage of fibromyalgia in females related to higher (abnormal) scores on functional and quality of life assessments.…”

Section: Drug Survival Studiesmentioning

confidence: 80%

Infection, malignancy, switching, biosimilars, antibody formation, drug survival and withdrawal, and dose reduction

Ianculescu

Weisman²

2016

Current Opinion in Rheumatology

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TNFi agents have made their powerful impact on management of patients with rheumatoid arthritis, but questions remain: what is their true infection and malignancy risk in the evolving populations using these drugs today; are we able to maintain their benefit with a reduced schedule (and presumed less cost) and yet recapture their benefit if we guess wrong; are biosimilars just as good, or even better with less cost; are there data to inform us about how to achieve successful switching among different mechanism of action TNFi agents? Finally, are we going to face the specter of cost containment causing change from innovator to biosimilars over which we have no control?

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Rate of discontinuation and drug survival of biologic therapies in rheumatoid arthritis: a systematic review and meta-analysis of drug registries and health care databases

Abstract: In RA, treatment with etanercept has a lower percentage of discontinuation than infliximab and adalimumab. Concomitant use of DMARDs, disease duration before treatment with a biologic and female sex predict time to discontinuation.

Cited by 126 publications

References 95 publications

Safety and Efficacy of Biological Disease-Modifying Antirheumatic Drugs in Older Rheumatoid Arthritis Patients: Staying the Distance

Safety and Efficacy of Biological Disease-Modifying Antirheumatic Drugs in Older Rheumatoid Arthritis Patients: Staying the Distance

Heterogeneity in Comparisons of Discontinuation of Tumor Necrosis Factor Antagonists in Rheumatoid Arthritis - A Meta-Analysis

Infection, malignancy, switching, biosimilars, antibody formation, drug survival and withdrawal, and dose reduction

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