An early-stage clinical trial shows combination therapy improves responses in hard-to-treat patients, despite missing its main goal.
A new early-stage clinical trial is raising cautious optimism about a potential combination treatment for people living with difficult-to-treat psoriatic arthritis.
Researchers reported results from the Phase 2a AFFINITY study, which tested whether combining two biologic therapies – guselkumab and golimumab – could improve outcomes for patients whose disease had not responded adequately to tumor necrosis factor inhibitors, one of the most commonly used treatment classes.
The findings, published in Arthritis & Rheumatology, suggest that while the study did not meet its primary goal, several secondary measures point to meaningful clinical benefits in certain patient groups.
“Although the primary endpoint was not achieved, secondary endpoints and exploratory analyses suggest that participants with TNFi-IR PsA, particularly those with elevated CRP, could derive clinically meaningful benefits with guselkumab and golimumab combination therapy, with no new safety concerns, warranting further investigation,” the researchers wrote.
The trial enrolled adults with active psoriatic arthritis who continued to have symptoms despite prior treatment.
Participants were randomly assigned to receive either a combination of subcutaneous guselkumab and golimumab or guselkumab alone, administered every four weeks.
Guselkumab is a fully human, dual-acting monoclonal antibody that binds the p19-subunit of IL-23 and CD64 on IL-23-producing inflammatory monocytes, potentially neutralising bioavailable IL-23 at its cellular source. It is approved in Australia for moderate-to-severe plaque psoriasis and active psoriatic arthritis.
Golimumab is a fully human monoclonal antibody that targets TNF, a key driver of inflammation in autoimmune diseases. It is approved for use in psoriatic arthritis as well as rheumatoid arthritis, ankylosing spondylitis and ulcerative colitis in Australia.
By week 24, 29% of patients receiving the combination therapy achieved the primary endpoint of minimal disease activity, compared with 22% of those on monotherapy – a difference that did not reach statistical significance.
However, other outcomes told a more encouraging story.
Nearly twice as many patients in the combination group achieved a 50% improvement in disease activity scores compared to those on guselkumab alone.
The combination therapy also produced higher response rates across several measures of joint improvement and was associated with greater gains in physical function reported by patients.
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The most striking results emerged from a subgroup of patients with elevated levels of CRP, a marker of systemic inflammation. Among these individuals, those receiving the combination therapy were substantially more likely to reach minimal disease activity and showed markedly higher response rates across key clinical benchmarks.
The researchers noted that this subgroup represented the intended population for future study, suggesting that inflammation markers may help identify patients most likely to benefit from dual biologic therapy.
Improvements in skin symptoms and related conditions such as dactylitis and enthesitis were similar between the two groups, indicating that the added benefit of combination therapy may be more pronounced in joint-related outcomes rather than skin manifestations.
Safety findings were also closely watched, given concerns about combining biologic agents that target different immune pathways.
The study reported no new safety signals through 36 weeks of follow-up, and notably, there were no cases of tuberculosis or opportunistic infections, known potential risks with immunosuppressive treatments.
Despite the promising signals, researchers noted that the study was relatively small and exploratory in nature. The failure to meet the primary endpoint means the results should be interpreted with caution, and larger, more definitive trials would be needed to confirm the benefits and better understand the risks.
Regardless of these shortcomings, the researchers said their findings highlighted a growing interest in combination biologic therapy as a strategy for patients with psoriatic arthritis who did not respond to existing treatments.
“In conclusion, among participants with active PsA and nonresponse or loss of response to a TNFi, the combination of the IL-23i, guselkumab, and the TNFi, golimumab, may confer clinically meaningful benefits in joint disease activity and physical function over guselkumab monotherapy, with no new safety findings as compared with the established profiles of either drug, warranting further investigation,” they wrote.
“Greater impact of combination therapy was seen among participants with higher levels of systemic inflammation at screening, which is known to drive joint disease activity and structural damage, suggesting that future studies should focus on this patient population.”
