Combined data from two Phase III trials indicate that brodalumab led to a significant improvement among patients with psoriatic arthritis (PsA) who failed to achieve a satisfactory response with conventional therapies.
PsA is a chronic inflammatory disorder that affects the joints, tendon sheaths, entheses and axial skeleton which can lead to severe joint damage and functional impairment. Conventional treatment involves the use of non-steroidal anti-inflammatories, corticosteroids and synthetic disease-modifying anti-rheumatic drugs. Where patients fail to achieve a satisfactory response with these therapies, a biologic drug can be initiated.
A team led by a group from the Swedish Medical Research Centre, Washington, US, has examined the efficacy of brodalumab in two randomised, double-blind placebo-controlled trials, in patients who had an inadequate response to conventional therapy. Trial participants were aged 18 years and over and had at least three tender and three swollen joints as well as active psoriatic skin lesions. In both trials, patients were randomised 1:1:1 to subcutaneous brodalumab 140mg or 210mg or placebo on day 1 and in the first two weeks and then once every two weeks through to the study end (week 24). The primary endpoint for both trials was ACR20 response, i.e., a 20% improvement in both tender and swollen joint count, assessed at week 16. Secondary endpoints, also measured at week 16, included an ACR50/70 and a PASI75, i.e., a 75% reduction in PASI (a measure of disease severity) score.
A total of 962 patients were randomised across both studies with a mean age of 49 years and an approximately 50:50 sex distribution (though this ratio varied slightly across the different groups). At week 16, pooled analysis from the two trials showed that the ACR20 response rate was 45.8% and 47.9% for brodalumab 140mg and 210mg respectively and 20.9% in the placebo arm (p<0.0001 in both cases vs placebo) and that this was maintained at week 24 (51% vs 53.6% vs 23.8%, comparison as before). Higher ACR50 response were achieved from week 2 for brodalumab 210mg although the absolute magnitude was unclear as the data was only presented graphically. A PASI75 was achieved by 52.4%, 75.5% and 10.4% of participants given brodalumab 140mg, 210mg and placebo respectively.
The studies did not generate any new safety signals and the authors concluded that brodalumab represented an effective additional treatment for PsA.
Citation Mease PJ et al. Brodalumab in psoriatic arthritis: results from the randomised phase III AMIVISION-1 and AMIVISION-2 trials. Rheum Dis 2020 doi:10.1136/ annrheumdis-2019-216835