Adalimumab-adbm, Reference Adalimumab Demonstrate Clinically Meaningful Improvements in RA

Results of a post hoc analysis of the VOLTAIRE-RA trial showed patients with moderate to severe rheumatoid arthritis (RA) treated with either the adalimumab reference product or the biosimilar adalimumab-adbm had clinically meaningful improvements and similar domain scores at weeks 12 and 24, according to research published in Rheumatology and Therapy.1 Additionally, a high proportion of patients had scores greater than or equal to normative values across treatment arms. This is particularly notable as it was a previously difficult to achieve treatment goal in other RA trials.

“If appropriate long-term treatment is not given, progressive functional impairments can result in reductions in health-related quality of life (HRQoL),” wrote a team of investigators led by Vibeke Strand, MD, associated with the Division of Immunology/Rheumatology at Stanford University School of Medicine. “The most commonly reported RA symptoms associated with negative effects on HRQoL include pain, physical function impairments, fatigue, and morning stiffness. These symptoms also predispose to impaired work productivity and inability to fulfill day-to-day activities.”

With this in mind, it is important to understand the impact of new treatment options, such as adalimumab-adbm, from a patient’s perspective when designing, performing, and reporting on clinical trials.2

VOLTAIRE-RA was a double-blind, phase 3 randomized controlled trial (RCT) that enrolled patients with RA aged 18 – 80 years old who were currently being treated with methotrexate. Eligible participants received 40 mg of the adalimumab reference product or the biosimilar via a subcutaneous injection once every 2 weeks for a 24-week period. Those who were in the reference cohort were re-randomized at week 24 to either continue the reference drug or switch to the biosimilar. Patients in the biosimilar cohort were dummy re-randomized to continue treatment with the biosimilar.

Investigators compared patient-reported outcomes, such as HRQoL, among patients with RA using the 36-Item Short Form Survey (SF-36) physical component summary (PCS) and mental component summary (MCS) as well as domain scores at baseline, week 12, and week 24. Results were defined as clinically meaningful if improvements were greater than or equal to minimum clinically important differences (MCIDs) of 2.5 for the PCS domain score and 5.0 for the MCS domain score. Spydergrams and the health utility SF-6D measure helped to quantify comparisons with age- and sex-matched norms as well as treatment-associated changes in domain scores. The comparisons across treatment arms were descriptive in nature.

Overall, no differences in PCS scores were observed between the biosimilar cohort and the reference cohort at baseline, week 12, or week 24. The reference product was slightly favored at baseline according to MCS scores, and differences at weeks 12 and 24 were comparably reflective of that.

Over 65% of patients in both cohorts had clinically meaningful improvements in PCS scores at weeks 12 and 24. Similarly, 56% reported improvements in MCS scores greater than or equal to MCID at these time points.

Similar proportions of patients treated with the reference product and the biosimilar had scores greater than or equal to age- and sex-matched normative values at week 24 (14 – 39% vs 15 – 36%, respectively) compared with baseline (1 – 17%).

“VOLTAIRE-RA represents the final step of the biosimilarity assessment for adalimumab-adbm versus adalimumab reference product,” investigators wrote. “In parallel with the equivalent efficacy of adalimumab-adbm and adalimumab reference product in VOLTAIRE-RA, substantial benefits were reported across a range of PROs in both treatment groups. Thus, the efficacy and safety profiles of adalimumab-adbm translated into clinically meaningful improvements in patient experience and perception.”

References

1. ^{Strand, V., Bender, S. & McCabe, D. Effects of Adalimumab-adbm Versus Adalimumab Reference Product on Patient-Reported Outcomes in Rheumatoid Arthritis: Results from VOLTAIRE-RA. Rheumatol Ther (2024). https://doi.org/10.1007/s40744-024-00687-w}
2. ^{Sanderson T, Morris M, Calnan M, Richards P, Hewlett S. What outcomes from pharmacologic treatments are important to people with rheumatoid arthritis? Creating the basis of a patient core set. Arthritis Care Res (Hoboken). 2010;62:640–6.}