Early secukinumab gives quicker relief and fewer escalations, yet standard methotrexate step-up achieves comparable outcomes.
A new multicentre randomised controlled trial has compared two treat-to-target strategies in patients with newly diagnosed psoriatic arthritis, providing important insights into the timing and sequencing of biological DMARD therapy.
The STAMP (Strategy Treatments Aiming at Minimal Disease Activity in Psoriatic Arthritis) trial evaluated whether an early intensive strategy with the IL-17A inhibitor secukinumab could improve outcomes compared with a conventional methotrexate-based step-up approach.
Results were published this month in The Lancet Rheumatology.
“To our knowledge, the STAMP trial is the first randomised controlled trial to directly compare two distinct treat-to-target strategies in newly diagnosed patients with psoriatic arthritis, addressing a major gap in the evidence base,” the researchers wrote.
“Previous research demonstrated that a treat-to-target approach is feasible in psoriatic arthritis, but there was no evidence on how early initiation of a biological disease-modifying antirheumatic drug (DMARD) compares to a conventional step-up regimen within a treat-to-target framework.
“These findings challenge the assumption that early treatment with a biological DMARD is mostly superior, as both strategies showed similar long-term outcomes. However, the faster clinical response and reduced treatment burden in the early intensive treatment group highlight potential benefits in disease domains such as skin and enthesitis.
“These insights are directly relevant to ongoing debates about the optimal timing and sequencing of biological DMARD therapies in psoriatic arthritis and provide a crucial foundation for updating future treatment guidelines.”
Conducted across 12 hospitals in the Netherlands, the open-label trial enrolled 120 DMARD-naive adults with recently diagnosed psoriatic arthritis who met CASPAR criteria and had at least two swollen joints.
Participants were randomised to receive either early intensive therapy with secukinumab 300mg subcutaneously every four weeks plus weekly methotrexate 15mg, with escalation to TNF inhibitors or apremilast if minimal disease activity was not reached; or standard step-up care starting with methotrexate at 15 mg weekly; escalating to 25mg; followed by sulfasalazine and TNF inhibitors as needed.
All patients received a single intramuscular methylprednisolone injection at baseline. The primary endpoint was the proportion of patients achieving an ACR50 response at six months.
The trial did not meet its primary endpoint. At six months, 42% of patients in the early secukinumab group and 35% in the standard care group achieved ACR50, a difference that was not statistically significant.
By 12 months, both groups reported similar outcomes, with 50% achieving ACR50, and comparable rates of ACR20, ACR70, and minimal disease activity.
Early benefits of secukinumab were observed, however, with significantly higher ACR20, ACR50, and minimal disease activity rates at three months, along with superior skin responses and higher rates of enthesitis and dactylitis resolution.
These differences diminished over time. Treatment retention was higher in the early secukinumab group, with 58% staying on initial therapy at 12 months compared with 30% in the standard care group.
Adverse events occurred at similar frequencies in both groups, with serious adverse events reported in 10% of early secukinumab patients and 8% of standard care patients.
No deaths were observed, and no unexpected safety signals emerged, supporting the feasibility of early IL-17A inhibitor use within a treat-to-target framework.
Although early intensive therapy accelerated symptom control, improved skin and entheseal outcomes, and reduced treatment escalation, it did not confer a statistically superior ACR50 response at six months compared with a standard step-up approach.
These findings suggested that adherence to treat-to-target principles, rather than the choice of initial therapy, was crucial for achieving meaningful clinical outcomes in newly diagnosed psoriatic arthritis, the researchers wrote.
Early IL-17A inhibition may offer specific advantages for patients with prominent skin or entheseal involvement, informing personalised treatment decisions.
“These results also highlight several advantages of early intensive treatment, including a faster clinical response, better control of entheseal and skin manifestations, and greater treatment retention with fewer therapy escalations,” the researchers wrote.
“These early clinical improvements are consistent with findings from the GOLMePsA trial, another strategy trial using golimumab as a first-line therapy, which did not meet its primary endpoint (PASDAS at month six), but demonstrated more favourable outcomes at earlier timepoints.
“Together, these results emphasise that early, intensive intervention within a treat-to-target strategy might accelerate symptom relief and enhance early disease control in psoriatic arthritis.”
The researchers noted the STAMP trial had several limitations, including its open-label design, which may have introduced bias, and the fact that patient-reported outcomes may have been influenced despite objective measures.
The study did not directly compare secukinumab with TNF inhibitors, limiting conclusions about relative efficacy between biologic classes.
Secondary outcomes should be considered exploratory since the primary endpoint was not met, and the trial was powered to detect a 28% difference in ACR50, whereas the observed difference at six months was only 7%, partly due to unexpectedly strong responses in the standard care group and slightly lower responses in the early secukinumab group, the researchers wrote.
“In conclusion, the STAMP trial demonstrates that both an early intensive strategy with a biological DMARD and a conventional standard of care step-up approach can achieve similar clinical outcomes when embedded in a treat-to-target framework,” they wrote.
“Although early secukinumab treatment was associated with faster symptom control and fewer treatment escalations, these benefits did not translate into superior primary endpoint attainment at six months.
“Future studies should focus on long-term structural outcomes, cost-effectiveness, and identifying patient subgroups who could benefit most from early targeted therapy.”
