Efficacy of biologic agents in improving the Health Assessment Questionnaire (HAQ) score in established and early rheumatoid arthritis a meta-analysis with indirect comparisons
Lillian Barra, MD Andrew Ha, MDLouise Sun, MD
Catarina Fonseca, MDJanet Pope, MD, MPH
Please address correspondence and reprint requests to: Dr Lillian Barra,
St. Joseph’s Health Care,
268 Grosvenor Street, Room D2-160, London, Ontario, N6A 4V2 Canada.
E-mail: lbarra2@uwo.ca
Introduction
Randomised controlled trials (RCTs) have demonstrated the efficacy of bio-logics in Rheumatoid Arthritis (RA). Currently, there are eight biologic drugs approved for the treatment of RA: infliximab, etanercept, adalimum-ab, golimumab, certolizumab (anti-tu-mour necrosis factor-alpha), rituximab (anti-CD20), abatacept (anti-CTLA-4) and tocilizumab (anti-Interleukin-6). Anakinra (anti-Interleukin-1) is also Methods
Literature search and study selectionWe performed a search of the follow-ing bibliographic databases from 1990 up to and including August 2012: Med-line Pubmed, Embase and the Cochrane Library. Our search strategy combined terms for ‘Rheumatoid Arthritis’, ‘Bio-logics’ and ‘the Health Assessment Ques-tionnaire’ (for full search strategy, see Supplementary Fig. 1). Four independent reviewers (L, AH, LS, CF) conducted Received on July 4, 2013; accepted in revised form on November 14, 2014.© Copyright ExpErimEntalCliniCal rhEumatology and
2014.
Competing interests: none declared.
approved for use in RA, but it is rarely used in RA. Meta-analyses of these RCTs ing the standard primary outcomes generally report efficacy us-of the American College of Rheuma-tology-20, 50 or 70 score (ACR20, ACR50, ACR70) (1). This composite measure of patients with at least 20%, 50% or is defined as the proportion 70% improvement in swollen joint count, tender joint count and in 3 of the 5 variables: physician global as-sessment, patient global assessment, patient pain, patient function and a laboratory (erythrocyte sedimentation rate or marker for inflammation C-reactive protein) (2, 3). Since the ACR20/50/70 score is a composite measure, it is unclear what the di-rection of the effect is for important patient-centered components, such as physical function which, is usually as-sessed using the validated Health As-sessment Questionnaire (HAQ) (3). Determining whether biologic agents can significantly improve HAQ scores is important because HAQ is known to predict future morbidity, mortality, and hospitalisations (4). In addition, decreases in HAQ scores are associ-ated with less disability and improved quality of life (5).
It is unclear whether certain biolog-ics are more efficacious than others at improving HAQ. Head-to-head RCTs of biologics are scarce and evidence synthesis using meta-analysis methods either do not report HAQ or have only compared anti-TNF agents (6-12). We have used a frequentist meta-analysis approach to compare the efficacy of different biologics at improving HAQ in -established RA for (i) DMARD-failures (ii) anti-TNF-failures and (iii) in early RA (ERA) .
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the search and study selection by title/abstract. Hand searches of the referenc-es in relevant papers were conducted to identify any additional articles. Two inde-pendent reviewers (LB and AH or LS and CF) subsequently reviewed the full text articles. If there were discrepancies, con-sensus was reached after the material was reviewed by the other 2 reviewers.
Inclusion criteria were: (i) randomised controlled trials, (ii) trial follow-up of at least 6 months, (iii) patients met ACR or ACR/EULAR criteria for RA (13-14); (iv) patients were >15 years of age, (v) baseline and at least one follow-up HAQ score at 6 and/or 12 months were reported. Doses of biologics used in clinical practice were included (and usual loading doses where applicable): adalimumab 40 mg every 2 weeks, in-fliximab 3mg/kg every 4 or 8weeks up to 10 mg/kg every 8 weeks, etanercept 50 mg every week, golimumab 50 mg every 4 weeks, certolizumab 200 mg every 2 weeks or 400 mg every 4 weeks, rituximab 1000 mg day 1 and 15 (with repeat dosing allowed as often as every 6 months), abatacept 500 mg (patient weight <60 kg), 750 mg (60–100 kg) and 1000 mg (>100 kg) every 4 weeks, and weeks. For studies that included both tocilizumab 4 or 8 mg/kg every 4 approved and unapproved drug doses, the study arm with the unapproved dose was omitted from the analysis. Open label extension studies were excluded. Other exclusions included: patients with non-RA as Juvenile inflammatory arthritis, psoinflammatory arthritis (such riatic arthritis, ankylosing spondylitis -and connective tissue disease), studies combining biologic agents, case reports, case series, cross-sectional studies, re-views, editorials, letters and data pub-lished only as abstracts.