Points to Consider for Clinical Development of Drugs Intended for Treatment of Psoriatic Arthritis in Japan

1. Introduction and Disease Overview

Psoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disease associated with psoriasis that presents heterogeneously with peripheral arthritis, enthesitis, dactylitis, axial disease, and skin/nail involvement. The Pharmaceuticals and Medical Devices Agency (PMDA) issued Points to Consider for Clinical Development of Drugs Intended for Treatment of Psoriatic Arthritis (Early Consideration) on November 13, 2025, to provide reference information on regulatory expectations for clinical development of PsA drugs in Japan.

2. General Clinical Development Strategy

2.1 Target Population and Disease Heterogeneity

Development plans should clearly define the target PsA population, considering its clinical heterogeneity. Subsets such as patients with predominant enthesitis, axial involvement, or minimal skin symptoms may require specific considerations in trial design and endpoint selection. Robust inclusion criteria help ensure appropriate evaluation of efficacy across key disease domains.

2.2 Use of Global Data and Multi-regional Trials

Given the global nature of PsA drug development and relatively limited patient numbers in Japan alone, multi-regional clinical trials (MRCTs) including Japanese patients are generally recommended. Use of foreign clinical data may be considered for efficacy evaluation if justified with supportive evidence demonstrating relevance to the Japanese population, such as similar pharmacokinetics and disease characteristics in Japanese subjects.

3. Efficacy Endpoints

3.1 Established Composite Endpoints

Clinical efficacy evaluation should include validated composite endpoints that reflect PsA’s multi-domain nature. Commonly used measures include:

• ACR Response Criteria (e.g., ACR20/50/70) for peripheral arthritis.
• Psoriasis Area and Severity Index (PASI) for skin manifestations when present.
• Minimal Disease Activity (MDA) criteria to assess broader disease control.
  Endpoints should be prespecified in protocols with clear definitions and rationale for their selection.

3.2 Domain-specific Measures

Specific domains such as enthesitis and dactylitis may require dedicated measures like the Leeds Enthesitis Index or dactylitis scores. Selection of domain-specific endpoints should align with the drug’s proposed mechanism of action and the clinical relevance of these manifestations to patients.

4. Study Design Considerations

4.1 Randomized Controlled Trials

Randomized, double-blind, controlled trial designs remain the regulatory standard for demonstrating efficacy and safety. Choice of comparator (placebo or active control) should reflect ethical and scientific considerations, particularly where effective therapies exist. Background therapies should be consistent across groups to minimize confounding.

4.2 Duration and Assessment Timing

PsA treatment effects may vary by domain and over time. Assessment timing should capture both early responses (e.g., at Week 12/16) and more sustained outcomes (e.g., at Week 24 or beyond) to fully characterize efficacy across disease domains.

5. Safety Monitoring and Special Population Considerations

Safety assessment should be comprehensive, including monitoring for infection, malignancy risk, and organ-specific adverse events relevant to the mechanism of action of investigational drugs. Plans should incorporate long-term safety follow-up when feasible. Special populations such as the elderly or those with comorbidities require tailored safety and efficacy evaluation.

6. Regulatory Engagement and Consultation

Early engagement with PMDA through scientific advice meetings is recommended to align on clinical development plans, endpoint selection, study design, and utilization of foreign data. Such interaction can reduce uncertainty and support efficient development pathways.

Summary

The PMDA’s Early Consideration outlines key principles for PsA drug development in Japan, emphasizing clear definition of target populations, selection of multi-domain efficacy endpoints, robust randomized trial designs, thoughtful incorporation of global data, and proactive regulatory consultation to ensure that evidence generated meets Japanese regulatory expectations.