Highlights
– The multicentre STAMP trial randomized 120 DMARD‑naive patients with early psoriatic arthritis to an intensive biologic‑first treat‑to‑target strategy (secukinumab + methotrexate) versus a conventional methotrexate‑first step‑up treat‑to‑target approach.
– Primary outcome (ACR50 at 6 months) was not significantly different: 42% with early secukinumab versus 35% with standard care (RR 1.19; 95% CI 0.75–1.88; p=0.45).
– By 12 months both groups achieved similar clinical improvement (about half of patients reaching ACR50), and safety profiles were comparable.
Background
Psoriatic arthritis (PsA) is a heterogeneous inflammatory arthropathy associated with psoriasis and characterized by peripheral arthritis, axial disease, enthesitis, dactylitis and skin and nail involvement. Early control of inflammation is important to prevent structural damage, preserve function and improve quality of life. Treat‑to‑target (T2T) approaches that set an explicit disease activity target and escalate therapy if the target is not met have been advocated for PsA and have shown improved outcomes in previous studies and guideline recommendations.
However, optimal sequencing of therapies within a T2T framework—specifically whether immediate intensive biologic therapy (biologic‑first) improves short‑ and medium‑term outcomes compared with a conventional csDMARD‑first step‑up approach—remains uncertain. Secukinumab, an IL‑17A inhibitor, is established as an effective biologic for PsA; whether early use of secukinumab confers clinically meaningful advantages when embedded in a T2T strategy was the question addressed by the STAMP trial.
Study design
STAMP was a pragmatic, multicentre, open‑label, randomized controlled trial conducted in 11 general hospitals and one academic centre in the Netherlands. Key eligibility criteria included age ≥18 years, newly diagnosed PsA meeting CASPAR criteria, at least two swollen joints at baseline and no prior exposure to any DMARD. Randomization was 1:1 to either an early secukinumab strategy or to standard of care (SOC) step‑up therapy. Patients and treating teams were aware of assignment (open‑label), but outcome assessment used standard clinical measures.
Interventions
Early secukinumab arm: subcutaneous secukinumab 300 mg at baseline and every 4 weeks plus weekly oral methotrexate 15 mg for up to 12 months. Minimal disease activity (MDA) was assessed every 3 months; if MDA was not achieved treatment was switched to a TNF inhibitor, then to a second TNF inhibitor if needed, and finally to apremilast if the second TNF inhibitor was stopped.
Standard of care arm: weekly oral methotrexate 15 mg escalating to 25 mg at 6 weeks for up to 12 months, with escalation according to routine clinical practice if MDA was not achieved. Both groups received a single intramuscular methylprednisolone 80 mg injection at baseline.
Outcomes and analysis
The primary outcome was the proportion of patients achieving an ACR50 response at 6 months in the intention‑to‑treat population. Safety was assessed in all patients who received at least one dose of study treatment. The trial was registered (ISRCTN76054545) and included patient representatives in design.
Key findings
Between December 2019 and October 2023, 120 patients were randomized (60 per arm). Mean age was 49 years, 41% were female, and the cohort was predominantly Dutch in ethnicity (98% of those with ethnicity data).
Primary outcome (6 months)
At 6 months, ACR50 was achieved in 25/60 (42%) patients in the early secukinumab arm versus 21/60 (35%) in the SOC arm. The relative risk was 1.19 (95% CI 0.75–1.88) with a p value of 0.45, indicating no statistically significant difference. Thus, the trial did not meet its primary endpoint.
Secondary and 12‑month outcomes
By month 12, both strategies yielded similar clinical improvements: approximately half of patients in each arm attained ACR50. The manuscript reports convergence of outcomes over time, suggesting that a T2T strategy with stepwise escalation can achieve results comparable to an initial biologic‑first approach within one year.
Safety
Adverse events were similar between groups: 30/60 (50%) in the early secukinumab group and 32/60 (53%) in the SOC group experienced at least one adverse event. Serious adverse events occurred in 6/60 (10%) versus 5/60 (8%), respectively. There were no deaths. Overall safety signals were consistent with known profiles of the therapies used.
Interpretation and clinical relevance
In patients with newly diagnosed, DMARD‑naive PsA and active peripheral synovitis (≥2 swollen joints), initiating therapy with secukinumab plus methotrexate did not provide a statistically significant advantage in achieving ACR50 at 6 months compared with a conventional methotrexate‑first T2T strategy. Over 12 months outcomes converged, with roughly half of patients in both arms attaining ACR50.
These results have several practical implications. First, they support the effectiveness of a well‑implemented T2T approach using conventional csDMARD initiation and escalation: when clinicians monitor disease activity and escalate therapy if targets are unmet, patients can reach substantial clinical responses within a year. Second, in resource‑constrained systems or where biologic access is limited, a methotrexate‑first T2T pathway appears a reasonable strategy without clear short‑term compromises in clinical response. Third, an immediate biologic‑first approach may not be necessary for all patients with early PsA, though individual patient factors (severity, extra‑articular disease, patient preference, radiographic risk) may justify earlier biologic use.
Methodological strengths and limitations
Strengths of the STAMP trial include randomized allocation, real‑world multicentre conduct across general and academic hospitals, inclusion of DMARD‑naive early PsA patients (a clinically relevant population), and embedding in a T2T framework with predefined escalation pathways. Patient involvement in design is also notable.
Key limitations:
- Open‑label design: awareness of treatment could influence patient‑reported outcomes and clinical behavior (though ACR50 includes objective joint counts which are less susceptible to bias).
- Sample size and power: the trial randomized 120 patients; the observed ACR50 difference at 6 months was modest and confidence intervals were wide, leaving open the possibility of a type II error for smaller but potentially clinically meaningful effects.
- Concomitant steroid and methotrexate use in both arms may have reduced between‑group differences early on; a single intramuscular methylprednisolone 80 mg and initial methotrexate (even in the biologic arm) could have promoted early improvement in both groups.
- Generalisability: the population was almost exclusively Dutch; results may not fully extrapolate to more ethnically diverse settings. Additionally, patients had peripheral polyarthritis (≥2 swollen joints) and were DMARD‑naive; findings may not apply to patients with dominant axial disease or those previously treated with DMARDs.
- Radiographic outcomes, structural progression, detailed domain‑specific (skin, enthesitis, dactylitis) results and patient‑reported outcomes beyond ACR50 were not summarized here; these elements are important for comprehensive assessment and may influence treatment choice.
- Industry funding (Novartis) is acknowledged; while common in trials of biologics, potential bias in design/reporting should be considered alongside the randomized design and peer‑reviewed publication.
Context with current practice
Contemporary guidelines generally endorse T2T principles in PsA and recommend individualized therapy based on disease domains, severity, comorbidities and patient preferences. Traditional algorithms often begin with csDMARDs (for peripheral arthritis) and escalate to biologics or targeted synthetic DMARDs for inadequate responders. The STAMP trial provides randomized data supporting the effectiveness of a csDMARD‑first T2T approach: when escalation is prompt and guided by disease activity targets, many patients achieve substantive improvements without immediate biologic therapy.
Unanswered questions and future research
Important areas for further study include:
- Longer‑term outcomes: structural damage progression (radiographic and imaging), sustained remission, functional outcomes and work productivity beyond 12 months.
- Domain‑specific benefits: whether early biologic therapy provides superior control of enthesitis, dactylitis, axial disease, or skin disease compared with step‑up strategies.
- Identification of subgroups who might benefit from biologic‑first strategies (biomarkers, clinical phenotypes, high radiographic progression risk).
- Cost‑effectiveness analyses comparing biologic‑first versus step‑up T2T strategies in different healthcare settings.
Conclusion
The STAMP trial adds pragmatic randomized evidence that, in patients with early, DMARD‑naive psoriatic arthritis and peripheral synovitis, an intensive biologic‑first treat‑to‑target strategy using secukinumab plus methotrexate did not confer a statistically significant advantage in ACR50 response at 6 months compared with a conventional methotrexate‑first step‑up T2T approach. By 12 months, outcomes were similar between strategies. These findings support continued use of treat‑to‑target principles with individualized escalation and underscore the need to tailor initial therapy to patient characteristics, disease domains and resource considerations.
Funding and trial registration
Funding: Novartis. Trial registration: ISRCTN76054545.
References
1. Koc GH, Kok MR, Kasiem FR, Luime JJ, Tchetverikov I, Wilhelm‑de Jong K, Korswagen LA, Denissen NHAM, Goekoop‑Ruiterman YPM, Baudoin P, Kok P, Bos R, Dolhain RJEM, Vis M. Intensive biological DMARD‑first strategy versus standard step‑up care in psoriatic arthritis (STAMP): 1‑year results from a multicentre, open‑label, randomised controlled trial comparing two treat‑to‑target strategies. Lancet Rheumatol. 2025 Nov 20:S2665‑9913(25)00223‑1. doi: 10.1016/S2665‑9913(25)00223‑1. Epub ahead of print. PMID: 41275881 .