medwireNews: Findings from the phase 3 AMVISION-1 and AMVISION-2 trials suggest that brodalumab may represent a promising treatment option for people with psoriatic arthritis (PsA).
“Brodalumab is a fully human monoclonal antibody with a unique mechanism of action that binds to the IL-17 receptor subunit A (IL-17RA) with high affinity and, as a consequence, blocks the action of multiple proinflammatory cytokines of the IL-17 family, beyond that of IL-17A alone,” say Philip Mease (Swedish Medical Center, Seattle, Washington, USA) and co-investigators.
They note that “[b]rodalumab 210 mg is currently approved for the treatment of moderate-to-severe plaque psoriasis in the USA, EU, Canada and certain Asian countries and for PsA currently only in Japan.”
The AMVISION-1 and AMVISION-2 studies included a total of 962 adults with active PsA and an inadequate response or intolerance to conventional treatment with nonsteroidal anti-inflammatory drugs or DMARDs. Participants were randomly assigned to receive subcutaneous brodalumab 140 mg, brodalumab 210 mg, or placebo once every 2 weeks following loading doses at weeks 0 and 1. Mease and colleagues note that data from both trials were pooled due to similar design and eligibility criteria.
As reported in the Annals of the Rheumatic Diseases, patients treated with brodalumab 140 mg or 210 mg had significantly higher ACR20 response rates at week 16 than those given placebo, at 45.8% and 47.9% versus 20.9%, respectively.
ACR50 (24.8 and 26.1 vs 7.2%) and ACR70 (11.3 and 12.2 vs 3.4%) response rates at week 16 were also significantly higher among participants in the brodalumab 140 mg and 210 mg groups versus those in the placebo arm, and the researchers say that ACR response rates were generally better with the higher dose of brodalumab.
Mease and colleagues also found that brodalumab improved skin, enthesitis, and dactylitis endpoints in the trials. For instance, at week 16 PASI75 response rates were significantly higher in the brodalumab 140 mg and 210 mg groups compared with the placebo arm, at 52.4% and 75.5% versus 10.4%, respectively. Rates of dactylitis resolution among people with the condition at baseline were 40.9% and 50.8% versus 24.2%, respectively, and the corresponding rates of enthesitis resolution were 42.3% and 39.1% versus 23.7%.
The investigators say that the AMVISION-1 and AMVISION-2 trials were terminated early following the sponsor’s decision to cease participation in the codevelopment of brodalumab after suicidal ideation and behavior (SIB) was identified as a potential risk during the drug’s development. Following discussion with the regulatory agencies, there was a protocol amendment excluding people with SIB from the trials.
In the safety analysis, Mease et al say that there were “[n]o major imbalances or emergent safety signals,” and that the rates of SIB were comparable in the brodalumab 140 mg, brodalumab 210 mg, and placebo arms (0.3 vs 0 vs 0%), “suggesting that brodalumab treatment did not increase the risk for depression and SIB among patients with no prior history.”
Taken together, “[t]he favourable safety profile and efficacy data from these trials suggest that inhibition of IL-17RA with brodalumab […] may represent an additional treatment strategy for patients with PsA,” conclude the investigators.
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