Golimumab for the treatment of rheumatoid arthritis after the failure of previous disease-modifying antirheumatic drugs: a NICE single technology appraisal.

As part of the National Institute for Health and Clinical Excellence (NICE) single technology appraisal (STA) process, the manufacturer of golimumab (Simponi(®); Merck Sharp & Dohme, USA) was invited to submit evidence for its clinical and cost effectiveness for the treatment of rheumatoid arthritis (RA) after the failure of previous disease-modifying antirheumatic drugs (DMARDs). The School of Health and Related Research Technology Appraisal Group (ScHARR-TAG) at The University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). This article provides details of the manufacturer's initial submission, the ERG's clarification questions and the ERG report submitted to NICE. The decision made by NICE is provided alongside a brief comment on additional results produced from an additional analysis requested by NICE on behalf of the Committee. The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based on upon the manufacturer's submission to NICE. The clinical evidence was derived from three randomized controlled trials of golimumab in the treatment of moderate to severe RA: GO-FORWARD and Kay et al. (DMARD-experienced population) and GO-AFTER (tumour necrosis factor [TNF]-α inhibitor-experienced population). The ERG considered that the trials were of reasonable methodological quality and measured a clinically relevant range of outcomes. The trials for golimumab, as well as comparator treatments, were synthesized using mixed-treatment comparison methods for the DMARD-experienced population and an indirect comparison using the Bucher method for the TNF-α inhibitor-experienced population. The trials used were appropriate, although no definitive judgement regarding the comparative efficacy of golimumab with other biologics was possible. The manufacturer provided a DMARD-experienced population model and a TNF-α inhibitor-experienced population model. The models allowed sequences of treatments to be evaluated for each population, although a fully incremental analysis between the use of golimumab following DMARD failure and the use of golimumab following TNF-α inhibitor failure was not possible. Several limitations with the model were identified, and after a request from NICE and suspension of the appraisal, the manufacturer submitted sensitivity analyses with an additional American College of Rheumatology 70 % improvement criteria (ACR70) health state included, using SF-36 data directly from the GO-FORWARD study. The annual rate of the Health Assessment Questionnaire (HAQ) score increase for patients receiving palliative treatment was also changed from 0.09 to 0.06. The further analyses provided highlighted the particular sensitivity of the results to HAQ progression rates and the re-administration frequency for rituximab in the TNF-α inhibitor-experienced population. The Appraisal Committee concluded that golimumab should be recommended in combination with methotrexate as an option for patients with severe active RA who have failed on conventional DMARDs, or who have failed on a TNF-α inhibitor and are contraindicated to or withdrawn from rituximab.