Highlights
- Early initiation of secukinumab in psoriatic arthritis (PsA) leads to faster clinical improvement compared to standard-of-care therapies.
- At 3 months, significantly more patients on secukinumab achieved ACR50 response (42% vs 22%).
- By 6 months and beyond, response rates converged between treatment arms, indicating no long-term superiority of secukinumab over stepwise escalation strategies.
- Early symptomatic relief may have meaningful implications for patient quality of life and treatment satisfaction.
Clinical Background and Disease Burden
Psoriatic arthritis (PsA) is a chronic, immune-mediated inflammatory arthritis associated with psoriasis, affecting up to 30% of patients with skin disease. Early, aggressive intervention is critical to limit joint damage, disability, and improve long-term outcomes. Traditional management often involves stepwise escalation from non-biologic disease-modifying antirheumatic drugs (DMARDs) to biologics in patients with inadequate response. However, delays in achieving disease control contribute to irreversible joint damage, impaired function, and reduced quality of life. There is increasing interest in treat-to-target (T2T) strategies and in whether early use of advanced therapies yields tangible clinical advantages.
Research Methodology
This randomized, open-label, multicenter trial enrolled 120 adults (mean age 49; 41% women) with PsA diagnosed within the preceding 3 months. Patients were randomized to one of two treat-to-target strategies:
- Secukinumab arm: 300 mg secukinumab monthly, a single 80 mg triamcinolone injection, 15 mg/week methotrexate (MTX), and 10 mg/week folic acid. Non-responders could escalate to a TNF inhibitor plus MTX.
- Standard-of-care arm: Single 80 mg triamcinolone injection, MTX starting at 15 mg/week and titrated up to 25 mg/week, and 10 mg/week folic acid. Escalation included addition of sulfasalazine, then switch to a TNF inhibitor plus MTX as needed.
Primary endpoint was the proportion of patients achieving ≥50% improvement per American College of Rheumatology criteria (ACR50) at 6 months. Secondary endpoints included minimal disease activity, ≥90% improvement in Psoriasis Area and Severity Index (PASI90), and resolution of enthesitis and dactylitis. Outcomes were measured at 3, 6, 9, and 12 months.
Key Findings
At the 3-month mark, the secukinumab group showed a marked advantage with 42% of patients reaching ACR50, compared to 22% in the standard-of-care group (P < .05). This rapid onset of action was reflected in secondary endpoints: more patients in the secukinumab arm achieved minimal disease activity, PASI90, and resolution of enthesitis/dactylitis at this early interval.
However, by 6 months, ACR50 rates converged (41% for secukinumab vs 37% for standard care). At 9 and 12 months, response rates remained numerically higher in the secukinumab arm, but differences were not statistically significant. Similarly, secondary endpoints demonstrated a pattern of faster initial response followed by convergence over time.
The rapid initial response may be particularly meaningful for patients seeking early symptom relief, although long-term disease control appears equivalent between modern stepwise and upfront biologic strategies in this population.
| Timepoint | ACR50 (Secukinumab) | ACR50 (Standard Care) |
|---|---|---|
| 3 months | 42% | 22% |
| 6 months | 41% | 37% |
| 12 months | Not statistically significant difference | Not statistically significant difference |
Mechanistic Insights
Secukinumab is a fully human monoclonal antibody that selectively inhibits interleukin-17A (IL-17A), a key cytokine in the pathogenesis of both psoriatic skin and joint inflammation. Rapid suppression of IL-17–mediated pathways may explain the observed early clinical benefits. In contrast, standard DMARDs like methotrexate act through broader immunomodulation and may require longer to achieve maximal effect.
Expert Commentary
Dafna Gladman, MD, a leading authority in psoriatic disease, emphasized the value of early symptom control: “Early response is very important to patients. They don’t necessarily care whether they are eventually going to catch up. They want to know they’ll feel much better at 3 months.”
These findings may influence shared decision-making, particularly for patients who prioritize rapid symptom relief.
Controversies and Limitations
This study’s strengths include its randomized design and focus on early PsA, a group with high unmet need. However, several limitations should be noted:
- Open-label design may introduce bias in patient- and physician-reported outcomes.
- Sample size (n=120) limits power for detecting smaller differences at later timepoints.
- Manufacturer sponsorship raises potential for conflict of interest.
- Results may not generalize to patients with established or treatment-refractory PsA.
- Longer-term safety and durability of early biologic intervention remain to be elucidated.
Conclusion
Early initiation of secukinumab in newly diagnosed PsA patients leads to faster clinical improvement and symptom relief compared to standard stepwise care, although long-term outcomes are comparable. For patients and clinicians prioritizing rapid disease control and quality of life improvement, upfront secukinumab may be a compelling option. Further research into cost-effectiveness, safety, and long-term joint protection is warranted to refine T2T strategies in PsA.
References
1. Mease PJ, et al. Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. N Engl J Med. 2015;373(14):1329-39.
2. Gossec L, et al. European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis. Ann Rheum Dis. 2020;79(6):700-712.
3. Koc GH, et al. Early secukinumab in PsA: Results from a randomized treat-to-target trial. Presented at: GRAPPA 2025 Annual Meeting, Bogotá, Colombia.
4. Gladman DD, et al. Treat-to-target in psoriatic arthritis: Where do we stand? Curr Rheumatol Rep. 2020;22(8):46.
