Management guidelines assume that results from clinical trials can be generalised, although seldom is data available to test this assumption. We aimed to determine the proportion of patients commencing tumour necrosis factor inhibition (TNFi) who would have been eligible for relevant clinical trials, and whether treatment response differs between these groups and the trials themselves. The British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS) recruited a real-world cohort of TNFi-naïve spondyloarthritis patients with data collection from clinical records and patient questionnaires. Participant characteristics were extracted from trials identified from a recent Health Technology Assessment of TNFi for ankylosing spondylitis/non-radiographic axial spondyloarthritis. Descriptive statistics were used to determine the differences, including treatment response, between BSRBR-AS participants who would/would not have been eligible for the clinical trials and with trial participants. Among 2420 BSRBR-AS participants, those commencing TNFi (34%) had shorter symptom duration (15 vs 22 years) but more active disease (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 6.4 vs 4.0; Bath Ankylosing Spondylitis Disease Functional Index (BASFI) 6.2 vs 3.8). Of those commencing TNFi, 41% met eligibility criteria for ≥1 of fourteen relevant trials; they reported higher disease activity (BASDAI 6.9 vs 6.1) and poorer function (BASFI 6.6 vs 6.0). 61.7% of trial participants reported a positive treatment response, vs 51.3% of BSRBR-AS patients (difference: 10.4%; 95% CI 4.4% to 16.5%). Potential eligibility for trials did not influence treatment response (difference 2.0%; -9.4% to 13.4%). Fewer patients in the real world respond to TNFi than is reported in the trial literature. This has important implications for the generalisability of trial results, and the cost-effectiveness of TNFi agents.
- ankylosing spondylitis
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Correction notice This article has been corrected since it published Online First. A minus sign has been added to difference 2.0%; -9.4% to 13.4% in the abstract.
Contributors GTJ and GJM designed the study and oversaw data collection (primary data). LED extracted the data (literature review). GTJ conducted the analysis and all authors were involved in interpretation of data. GTJ drafted the manuscript to which all authors provided critical contribution. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. All authors have given final approval of the version to be submitted for publication and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Funding This work was supported by the British Society for Rheumatology (BSR) who funded the BSRBR-AS. The BSR received funding for this from Pfizer, AbbVie and UCB. These companies receive advance copies of manuscripts for comments but have no input in to the topics for analysis in the register nor the work involved in undertaking analysis. Analysis of data was supported by the Versus Arthritis/Medical Research Council Centre for Musculoskeletal Health and Work (grant number 20665).
Competing interests None declared.
Patient and public involvement The British Society for Rheumatology’s Registers Committee, which oversees the running of the BSRBR-AS, has patient representation from several arthritis charities, including the (UK) National Axial Spondyloarthritis Society. Although no patients or public were involved in the analysis for this manuscript, the research question was identified at a priority setting exercise involving scientists, rheumatology consultants, and patient representatives.
Patient consent for publication Not required.
Ethics approval The study was approved by the National Research Ethics Service (NRES) Committee North East – County Durham and Tees Valley (Research Ethics Committee (REC) reference 11/NE/0374).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis are available to external investigators, on reasonable request. For information on how to access data, see: http://www.rheumatology.org.uk/.