Points to Consider for Clinical Development of Drugs Intended for Treatment of Psoriatic Arthritis — PMDA Early Consideration Summary

In Plain Language

Psoriatic arthritis (PsA) combines joint inflammation with psoriasis and can affect several parts of the body, so a single measure may not capture all of its effects. The document discusses how sponsors can plan development studies that assess the drug in patients resembling those who may receive it in clinical practice. It recommends considering multinational clinical trials early, while evaluating possible ethnic differences for each investigational drug. For confirmatory trials, it describes a randomized, double-blind, controlled design and currently considers the American College of Rheumatology (ACR) response rate an appropriate primary efficacy endpoint. It also emphasizes assessing other PsA manifestations and, for pediatric development, considering what adult and pediatric data may support the evidence package. These considerations are intended to help evaluate benefits across the varied symptoms of PsA while taking account of Japan’s development and patient-enrollment context.

What This Guidance Covers

The document sets out PMDA’s key considerations for clinical development of drugs intended to treat PsA. It addresses development strategy, confirmatory trials and development for children. It is concerned with both the clinical manifestations of PsA and the way clinical studies can assess treatment effects in the populations for whom a drug is intended.

The discussion of development strategy focuses on the use of multi-regional clinical trials (MRCTs), in which patients from more than one region participate. The confirmatory-trial section covers study design, patient selection, efficacy endpoints and assessment timing. The pediatric section discusses planning, possible study approaches, use of data from adult PsA and pediatric psoriasis populations, and the practical challenge of enrolling Japanese children with PsA.

The document does not present a complete clinical-development program for a specific drug, nor does it set out a single trial design or endpoint for every investigational product. It notes that plans, including trial protocols and data packages, should be discussed with PMDA for individual products. Its considerations reflect the knowledge available at publication and may change as new evidence emerges.

Why It Matters

PsA is a chronic inflammatory disease with joint symptoms and psoriasis. The document describes enthesitis— inflammation where tendons, ligaments and other soft tissues attach to bone—as a predominant joint manifestation. Symptoms may affect peripheral joints and axial joints, including the spine; other characteristic features include nail psoriasis and dactylitis. Because these manifestations vary, evaluating only one aspect of the disease may give an incomplete picture of treatment effects.

Treatment aims described in the document include improving quality of life by alleviating or resolving joint symptoms and preventing irreversible joint destruction. A treat-to-target approach sets treatment goals and timelines; remission, meaning absence of disease activity in PsA, is the ideal target, but the document notes that it can be difficult to achieve. Minimal or low disease activity may therefore guide treatment decisions in many patients.

The document also responds to changes in drug development. Applications for PsA therapeutics are increasingly based on MRCT data. At the same time, the reported prevalence of PsA among patients with psoriasis in Japan is approximately 8 to 13%, making a Japan-only confirmatory trial with enough participants to evaluate efficacy and safety challenging. For pediatric PsA, the document anticipates that Japanese enrollment in trials may be extremely low or absent because the number of patients is limited. These factors make study planning, evidence from other regions and the selection of disease measures important considerations.

Key Recommendations

1. Consider multinational development early. Given the challenge of obtaining a sufficient sample size in Japan alone, MRCTs are recommended to be actively considered from an early stage. This follows evaluation of potential ethnic differences in pharmacokinetics and other factors for each investigational drug. If Japan’s participation in an MRCT is considered inappropriate, or concerns arise such as observed ethnic differences in pharmacokinetics, sponsors are recommended to consult PMDA about the development strategy.

2. Design confirmatory trials to fit the intended clinical position. Confirmatory trials should be randomized, double-blind, controlled trials, with appropriate control group(s) selected in light of the anticipated clinical positioning of the investigational drug in PsA treatment. An active comparator that has a similar clinical positioning may be considered; a placebo control is generally expected.

3. Choose a study population that reflects intended use. Inclusion and exclusion criteria must be established to select patients appropriate for evaluating the drug’s efficacy and safety in the target population anticipated in clinical practice. The document gives two examples: Bio-Naïve patients, who have had an inadequate response to conventional treatments but have not previously received biologics; and Bio-IR patients, who have had an insufficient response to biologic treatment in addition to conventional treatments. If the drug is intended for both groups, it is appropriate to evaluate its efficacy and safety in each population.

   Separate confirmatory trials for these groups are one option. A single trial including both groups may be considered if prior exploratory trials have demonstrated no significant differences in efficacy and safety between them. For this combined-trial approach, stratified randomization using “Bio-Naïve patients/Bio-IR patients” as stratification factors is preferable to enhance comparability between subgroups.

4. Use an endpoint strategy that reflects the range of PsA manifestations. The document considers it ideal to evaluate whether minimal or low disease activity can be attained. However, because there is no comprehensive index that evaluates the diverse clinical symptoms of PsA, most current trials use the ACR response rate, which focuses on joint symptoms, as the primary endpoint. At present, it is considered appropriate to use ACR response as the primary endpoint and include Minimal Disease Activity (MDA) criteria and other measures as secondary endpoints. The results should be evaluated comprehensively.

   Higher ACR response thresholds, such as ACR20, ACR50 or ACR70, are desirable in light of the approval status of existing PsA treatments. The specific threshold is appropriate to determine based on the investigational drug’s benefit-risk balance, its target population in clinical practice and its clinical positioning. If MDA is proposed as a primary endpoint, consultation with PMDA before study initiation is recommended, after careful examination of its appropriateness.

5. Assess efficacy at an appropriate time and beyond the primary assessment. The primary endpoint assessment is considered appropriate within 12 to 24 weeks of administration, in light of the Japanese clinical practice guidelines’ recommendation to assess treatment efficacy approximately 3 to 6 months after treatment starts. Because PsA requires long-term treatment, the document also emphasizes evaluating additional time points, such as 52 weeks, to assess longer-term efficacy.

6. Plan pediatric development during adult development. It is desirable to plan a pediatric PsA development program while developing the drug for adults with PsA. Depending on the information available, trials to evaluate efficacy and safety in children could be considered; extrapolation approaches and modeling and simulation could also be appropriate. The document recommends advance consultation with PMDA about pediatric development programs.

   When planning pediatric PsA trials, Japan’s participation and enrollment of as many Japanese patients as possible are recommended, provided that no significant ethnic differences are anticipated. Because enrollment may nevertheless be very low or absent, sponsors need to carefully evaluate whether efficacy and safety for Japanese children can be assessed primarily from trials in non-Japanese children, taking into account whether efficacy and safety differences exist between Japanese and non-Japanese adults with PsA.

Practical Implications

Interpretation: The recommendations point to several decisions that should be addressed together rather than in isolation. A proposed study population, comparator and endpoint should make sense in relation to the drug’s intended place in treatment. For example, a trial intended to support use in both Bio-Naïve and Bio-IR patients needs a plan to evaluate both populations; if they are combined in one trial, the document identifies stratified randomization as preferable when the stated condition is met.

For sponsors and regulatory teams, early planning includes assessing whether an MRCT can support development in Japan and considering the investigational drug’s pharmacokinetic profile and other factors that may relate to ethnic differences. The document specifically recommends consulting PMDA when Japan’s participation in an MRCT is considered inappropriate or when concerns such as pharmacokinetic differences arise. It also recommends advance consultation when planning pediatric development and, if considering MDA as the primary endpoint, before the study begins.

For statisticians and trial teams, the endpoint plan should distinguish the primary measure from the secondary measures that capture other disease manifestations. Timing should account for the stated 12-to-24-week window for the primary endpoint and the value of longer-term assessment, such as at 52 weeks. For pediatric programs, teams may need to assess whether available data can support extrapolation, while carefully considering the evidence for similarity or difference between Japanese and non-Japanese patients.

Technical Details

The endpoint and population terms below are central to the document’s considerations. The descriptions retain the definitions and thresholds provided in the source.

The ACR response rate is the document’s currently appropriate primary endpoint approach because it focuses on joint symptoms important to PsA management. The document does not identify one threshold as suitable for every investigational drug; the specific threshold is to be determined in relation to the benefit-risk balance, intended population and clinical positioning.

MDA is a composite measure that includes joint symptoms, enthesitis and psoriatic skin lesions. The document notes its potential to assess diverse PsA manifestations and its use as a secondary endpoint in development of several drugs. It also states that consensus in Japan has not been established on its validity, including the clinical relevance of its outcomes and correlations with other efficacy endpoints. For that reason, the document does not consider it ready for active recommendation as a primary endpoint in confirmatory trials.

For secondary endpoints, the document gives examples that pair clinical signs with measures:

The ACR response and MDA criteria address different aspects of assessment: the former is used to measure improvement in joint symptoms and related measures, while the latter is a composite threshold for minimal disease activity across specified criteria. The document’s approach is to include a range of relevant secondary measures and interpret the findings together, rather than relying on one outcome to represent all PsA manifestations.

Who Should Read It

This document is relevant to sponsors developing treatments for adult or pediatric PsA, particularly when planning an MRCT or a confirmatory trial. Clinical and regulatory teams can use it to identify the study-design and consultation considerations described by PMDA. Statisticians and trial designers may find the population, stratification, endpoint and timing discussions useful when developing a protocol. Investigators and medical writers may also find the descriptions of disease manifestations and outcome measures helpful when reviewing trial objectives or explaining how the study assesses PsA.

Official PMDA Source

• Official title: Points to Consider for Clinical Development of Drugs Intended for Treatment of Psoriatic Arthritis(Early Consideration)
• Issuing body and office: Pharmaceuticals and Medical Devices Agency, Office of New Drug IV
• Date on the document: November 13, 2025
• PMDA PDF: Official document (PDF)
• PMDA list page: PMDA Early Consideration documents

Source: Pharmaceuticals and Medical Devices Agency (PMDA) website, PMDA Early Consideration documents. This page was created by editing and summarising the PMDA document.

Consult the official document; this summary does not replace it. PMDA provides the English version for reference, and if it differs from the Japanese original, the Japanese original prevails.

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