Guselkumab response appears to be on par with first-line biologic therapies for adults with active PsA, treating their broad spectrum of symptoms with no new safety concerns, according to two concurrent clinical trials.
Guselkumab response appears to be on par with first-line biologic therapies for adults with active PsA, treating their broad spectrum of symptoms with no new safety concerns, according to two concurrent clinical trials.
On July 14, the FDA announced its approval of guselkumab, a human monoclonal antibody, for the treatment of active PsA.
TNF inhibitors have been the biologics of choice for active PsA; however, some patients don’t tolerate methotrexate, which is used in combination with anti-TNF therapies to enhance their response.
Unlike existing therapies and other treatments targeting inflammatory cytokines, guselkumab selectively inhibits IL-23 by targeting the cytokine’s unique p19-subunit. IL-23 is linked to the development of the skin and joint manifestations of PsA through its downstream counterparts, TNF and IL-17.
The FDA’s approval of guselkumab for adults with active PsA was announced four months after two concurrent phase 3 clinical trials testing the drug’s efficacy and safety were reported in The Lancet.
DISCOVER-1 involved patients with active PsA who had an inadequate response to standard treatments, including those previously treated with TNF inhibitors, while DISCOVER-2 recruited patients with active disease despite standard treatments but no previous exposure to biologics.
The hope was that guselkumab might provide greater benefit than TNF and IL-17 inhibitors since its target, IL-23, is upstream of both.
Patients receiving guselkumab, either once a month or every 8 weeks, did show significant improvements in joint symptoms and physical function, in the same ballpark as anti-TNF and IL-17 therapies. Over 30% more people on treatment achieved ACR20 at 24 weeks than the placebo group in both DISCOVER trials.
More positively, guselkumab had pronounced effects on the skin symptoms of psoriasis. Monthly guselkumab also reduced structural joint damage compared to placebo up to 24 weeks.
According to Professor Peter Nash, from the Sunshine Coast Rheumatology Research Unit, there was also evidence of an axial response to guselkumab, referring to the supplementary results reported by DISCOVER-1 investigator Philip Helliwell at the EULAR conference in June.
Professor Nash, who was involved in the DISCOVER trials, said this was considered a limitation for IL-23 inhibitors so the results are encouraging. “It looks like an advance and an alternate first-line choice, but we’re going to need head-to-head trials to work out which drug is superior,” he said.
His colleague Professor David Nicholls agreed, but said that guselkumab’s safety profile is most advantageous. “There aren’t very many drugs where the chances of getting a side effect that means you have to stop treatment is only 1-2 per cent.”
Dr Rani Sinnathurai, a rheumatologist at Royal North Shore Hospital, said guselkumab might give PsA patients another option. “It appears well tolerated and its less frequent dosing schedule may be preferred by some patients,” she said.
However, she cautioned against generalising the results to Australian patients because their access to biologics differs to the trials’ eligibility criteria. Australian patients must have trialled two conventional DMARDs for severe disease before qualifying for PBS-subsidised biologic therapies, whereas DISCOVER patients could be eligible after just 4 weeks on NSAIDs.
DISCOVER-1 and DISCOVER-2, The Lancet 2020, 4 Apr
