Cyclosporine Or Methotrexate for Pediatric Alopecia Areata: Routine Clinical Care Effectiveness Study

Rationale: Alopecia areata (AA) is a dermatological disorder characterized by non-scarring hair loss, significantly affecting the quality of life of patients. While some patients experience spontaneous hair regrowth or respond well to localized treatments, patients with moderate-to-severe AA represent a subgroup that requires systemic therapies for effective management. If the disease is severe and systemic treatment is desired, cyclosporine or methotrexate is initiated. Currently, the clinical management of moderate-to-severe AA is primarily based on expert opinions. There is a lack of research on systemic treatments for moderate-to-severe AA, comprising only a small number of randomized controlled trials and observational studies. There is a clear absence of long-term, prospective, and comparative data on these systemic therapies. Most conventional systemic treatments for AA are prescribed off-label, underlining the importance of gaining a more comprehensive understanding of their effectiveness and safety.

Since the introduction of Janus kinase (JAK) inhibitors, there has been a significant advancement in the treatment of pediatric alopecia areata. As of 2024, Ritlecitinib-a selective JAK3 inhibitor-has been approved for reimbursement in adolescents aged 12 years and older with severe disease (defined as SALT50 or greater). Eligibility for this treatment requires prior failure of systemic therapies such as cyclosporin or methotrexate. However, the choice between methotrexate and cyclosporin as first-line systemic treatment is not supported by robust comparative studies and is largely based on expert opinion, resulting in considerable (inter)national variation in clinical practice.

Therefore, the investigators conduct a patient preference trial with a long-term follow-up provided in the Pediatric Systemic Alopecia Areata Registry (STA2R-Pediatric). This study will evaluate the effectiveness of Cyclosporin (CsA) and Methotrexate (MTX) in children and adolescents with moderate-to-severe AA. Aiming to provide valuable insights into the effectiveness, safety, and long-term outcomes of these therapies. By collecting and analyzing such data, this study endeavors to contribute to evidence-based clinical management, ultimately improving care for children and adolescents with AA.

Objective(s): To investigate the effectiveness of CsA and MTX in the treatment of children and adolescents with alopecia areata in routine clinical care.

Study type: This is a prospective, patient preference clinical trial with a duration up to 36 weeks in accordance with the routine clinical care guidelines after which patients will be followed in the STA2R-Pediatric (PANAMA-ID 11347).

Study population: This study will include children and adolescents (2-17 years old) diagnosed with AA who start first-line systemic treatment.

Methods: Patients and their parents will choose between CsA and MTX treatment as in routine clinical care, receiving follow-up in accordance with standard clinical practices. They will not be randomized. The primary endpoint is the measurement of the Severity of Alopecia Tool (SALT) at 9-months, providing a quantitative assessment of the disease's activity and response to the selected treatment. SALT scores will be measured by a blinded assessor. The (Children) - Dermatology Life Quality Index ((C)-DLQI) questionnaire will be conducted at each visit (0, 3, 6, 9 months), allowing evaluation of the impact on patients' quality of life.

Burden and risks: Participants in this study will receive treatment according to standard clinical practice protocols. The only addition to their routine care will be one questionnaire at each visit, that takes no more than 5 minutes to complete. The investigators consider this to be a negligible risk.

Recruitment and consent: Eligible patients will be identified at the dermatology outpatient clinic. During a routine visit to the outpatient clinic, the dermatologist will explain the study to the patient and the patient will be asked whether they would be willing to participate in the study. Patients will have the opportunity to ask any questions to clarify their understanding and concerns about the study. The Patient Information Form, Informed Consent Form, and instructions on how to proceed if they are interested in taking part or finding out more about the study will be given to the patient and their parents. During this visit the physician involved in the study will inform the patients and answer all the questions, Informed Consent can be obtained during the same visit. The Informed Consent will be completed and signed by the patient, their parents, and the physician. For patients under 12 years of age, consent will be signed by the parents only.

• SALT 24 weeks [Time frame: 24 weeks]
• Quality of life (DLQI) [Time frame: 24, 36 weeks]
• Adverse events [Time frame: 0, 12, 24, 36 weeks]
• Discontinuation of therapy [Time frame: 0, 12, 24, 36 weeks]