Combined Low Dose Oral Minoxidil and Immunomodulator Efficacy and Safety in Alopecia Areata: A Systematic Review

Many practitioners elect to add low-dose oral minoxidil (LDOM) to various systemic immunomodulatory agents, including Janus kinase inhibitors (JAKis), in hopes of improving treatment outcomes in patients with alopecia areata (AA). This systematic review aims to document, synthesize, and critically appraise the current literature on combination LDOM and systemic immunomodulators for the management of AA. MEDLINE, Embase, CENTRAL, Scopus, and Web of Science were searched from database inception to April 22, 2025, using subject headings and key terms relevant to oral minoxidil and AA. A PROSPERO protocol was registered (CRD420250651072), and PRISMA 2020 reporting guidelines were followed [1]. Eligible studies consisted of those reporting the safety and efficacy of concurrent LDOM and systemic immunomodulators in patients with AA. Abstracts, non-English texts, and reviews were excluded. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklists [2], revealing a ten-to-nine split between low/moderate risk (https://doi.org/10.17632/xdgfrxw54s.1). Nineteen studies (ten case reports/series, nine cohort studies), encompassing 388 patients with AA who received concurrent LDOM with systemic immunomodulators, were identified, of whom 54.4% were female with a mean age of 29.9 years (range: 3–87) (Table 1; Table S1 https://doi.org/10.17632/xdgfrxw54s.1). The most frequently studied immunomodulator combined with LDOM was oral tofacitinib (209/388, 54%), followed by oral baricitinib (152/388, 39%). Tofacitinib was commonly administered at 5 mg BID, and baricitinib at 4 mg OD. Mean follow-up duration was 16 months (range: 6–44). In studies clearly reporting adverse events, patients experienced hypercholesterolemia (19/145, 13.1%), transaminitis (15/145, 10.3%), hypertrichosis (10/145, 6.9%), neutropenia (7/145, 4.8%), and elevated creatinine (4/145, 2.8%), among others (Table 1). Complete hair regrowth (defined as a SALT of 0) was reported with LDOM and oral tofacitinib (16/32, 50.0%), or with oral corticosteroids plus azathioprine or cyclosporine (7/11, 63.6%), dupilumab (2/3, 66.7%), or ritlecitinib (0/1, 0%). Two studies explicitly compared dual therapy (mini-pulse dexamethasone or tofacitinib with LDOM) to systemic monotherapy, and reported non-significant SALT score differences (p = 0.88, p = 0.62) [3, 4]. Adverse events were either non-significant (p = 0.65) [4] or not reported between dual and monotherapy groups [3]. In this cohort, SALT ≤ 20 was achieved in 71.4% (60/84) of patients receiving LDOM and any JAKi (mean follow-up 22.2 months, n = 58) (Table 2). This is significantly higher than the 36.8%–40.9% of patients treated with 4 mg baricitinib monotherapy in the BRAVE-AA1/AA2 trials who achieved a SALT ≤ 20 at Week 52 (Z = 4.95, p < 0.00001) [5], though this comparison is imperfect. Due to limited consistent reporting on definitions of complete response, a sub-analysis of SALT ≤ 20 scores could not be performed. With incomplete reporting on LDOM dosing, a dose response effect of LDOM could not be determined. Combination LDOM-JAKi therapy may improve JAKi efficacy, but data to support this remain relatively weak at the present time. Despite these promising findings, current evidence is limited by small sample sizes and potential publication bias. Future studies should prioritize larger studies, extended follow-up periods, and refined patient selection criteria. A randomized controlled trial comparing LDOM monotherapy to combination LDOM-JAKi treatment groups is needed to assess the efficacy and safety of combination therapy in AA. The authors have nothing to report. No AI was used in the writing of this manuscript. C.S. has received honoraria from Abbvie, Leo, Pfizer, Miravo, Novartis, UCB, Sanofi/Regeneron unrelated to this work. J.D. has received honoraria from Pfizer and Vichy, has participated on advisory boards at Pfizer for payment, has received royalties from UpToDate, participates on the Board of Directors for the Scarring Alopecia Foundation, and is the active Director of the Evidence Based Hair Training Program. A.M. has received honoraria or consulting fees from hims and hers, AbbVie, Sun Pharma, Pfizer, Digital Diagnostics, Lilly, Equillium, ASLAN, Boehringer Ingelheim, Dermatheory, Olaplex, Legacy Healthcare, and Pelage. All other authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.

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