Clinical and Cost Effectiveness in Switching From Innovator to Biosimilar Infliximab

The Canadian Agency for Drugs and Technologies in Health (CADTH), an independent, nonprofit organization tasked with providing objective evidence for healthcare decision makers, reviewed the clinical effectiveness, cost-effectiveness, and advice from guidelines concerning switching from innovator to biosimilar infliximab for the treatment of several autoimmune diseases: rheumatoid arthritis (RA), ankylosing spondylitis (AS), plaque psoriasis (PP), Crohn’s disease (CD), Crohn’s disease (UC), and psoriatic arthritis (PA). The CADTH report used 273 citations from the literature on the topic, including abstracts from 69 conferences, and addressed the following issues:

• Clinical efficacy and safety of switching from innovator to biosimilar infliximab for patients with RA. Efficacy was based on well-known clinical markers for RA, such as the American College of Rheumatology’s (ACR) ACR20, ACR50, and ACR70 response rates. Safety was based on frequency of adverse events (AEs).

The report identified 2 single-arm extension studies of randomized clinical trials in Europe and Japan that suggested similar effectiveness and safety for RA patients who received a maintained biosimilar or who had switched to biosimilar. The studies further demonstrated that clinical response and safety profile were maintained long-term with the biosimilar.

• Clinical efficacy and safety of switching from innovator to biosimilar infliximab for patients with AS. Commonly accepted clinical markers for AS were used for efficacy endpoints and safety was based on the frequency of adverse events.

A single-arm 1-year extension study showed that switching from originator infliximab to a biosimilar is possible without compromising efficacy or safety in patients with AS.

• Clinical efficacy and safety of switching from innovator to biosimilar infliximab for patients with PP. The Psoriasis Area and Severity Index (PASI) and visual analogue scale score for arthritic pain, as well as AEs, were used to measure effectiveness and safety.

One single-center cohort study found no significant differences in the PASI and visual analog scale for arthritic pain score after all patients in the cohort were switched to biosimilar infliximab. There were no AEs resulting in discontinuation; 1 patient experienced a herpes zoster infection that resolved after treatment.

• Clinical efficacy and safety of switching from innovator to biosimilar infliximab for patients with CD or UC. Commonly accepted disease activity scales for CD and UC, as well as C-reactive protein levels, were used to determine clinical effectiveness. Frequency of AEs was used to determine safety.

A 1-year observational cohort study that included 12 patients who switched from reference to biosimilar infliximab to reduce costs showed that, at week 48, 87.5% of the 8 remaining patients had a sustained clinical response. The mean Short Inflammatory Bowel Disease Questionnaire score did not change significantly. Two patients (25%) discontinued treatment with biosimilar infliximab due to psoriasiform dermatitis and loss of response.

• Cost effectiveness of switching from innovator to biosimilar infliximab. One systematic review and 2 budget impact analyses suggest that there are cost savings generated by switching from innovator to biosimilar infliximab. The systematic review found that cost savings would be substantial, though the exact amount depends on the rate of interchangeability, patient number, eligibility, and the actual cost of the biosimilar.

Although the authors tried to locate data on the clinical efficacy and safety of switching from innovator to biosimilar infliximab for patients with PA, they were unable to identify relevant studies. In addition, despite searching for evidence-based guidelines regarding switching from the innovator to the biosimilar, none were identified.

In conclusion, the report found a suggestion that switching may be possible without compromising efficacy or safety. However, the authors caution that their findings must be interpreted carefully, because for most conditions, the findings were from single studies, some of which were small in size. There was also a lack of cost-effectiveness studies. Although higher-quality trials would aid in policy decision making, the report states, the studies consistently demonstrated the potential for cost savings after the introduction of an infliximab biosimilar.