Original Article

Efficacy and Safety of Tofacitinib in Lichen Planopilaris: A Retrospective Series of 74 Patients

Cite this article as: Goodarzi M, Dadkhahfar S, Yahyaei F, Razzaghi Z, Moravvej H. Efficacy and safety of tofacitinib in lichen planopilaris: a retrospective series of 74 patients. Arch Iran Med. 2025;28(1):24-28. doi: 10.34172/aim.33237

Introduction

Lichen planopilaris (LPP) is an inflammatory condition characterized by the progressive destruction of hair follicles, leading to scarring alopecia.¹ As a variant of lichen planus, it primarily affects the scalp but can occasionally involve other body parts.² LPP is more common in females and typically starts between the ages of 40 and 70, and it is rare in children.^3-6 The etiology of LPP remains poorly understood, although it is thought to have an autoimmune component.⁷ Patients with LPP often experience significant psychological distress due to irreversible hair loss and scalp discomfort.⁸ The main treatment objectives are to prevent the advancement of hair loss, alleviate symptoms, and preserve the existing hair follicles.⁹ Traditional treatment options, including corticosteroids and immunosuppressive agents, have had limited success, underscoring the need for more effective clinical treatments.⁹

Tofacitinib, a Janus kinase (JAK1,3) inhibitor, has emerged as a promising treatment for various autoimmune diseases due to its ability to impair the JAK-STAT signaling pathway, which communicates extracellular signals to the cell nucleus, thereby affecting DNA transcription.^10-12 Its efficacy has been well-documented in conditions such as rheumatoid arthritis, psoriasis, and alopecia areata, and emerging evidence suggests potential benefits in treating other autoimmune dermatological disorders, including LPP.^13-15 By inhibiting specific pathways involved in the inflammatory process, tofacitinib may offer a novel approach to managing LPP, providing relief from symptoms and possibly halting disease progression.^16-18

This retrospective study aims to investigate the efficacy of tofacitinib in patients with LPP who were referred to a tertiary referral center from 2020 to 2022. By analyzing patient records, treatment outcomes, and side effects, this study seeks to provide valuable insights into the potential role of tofacitinib in managing LPP. Our research findings will contribute to the growing body of literature on the use of JAK inhibitors in dermatology and may lead to improved treatment approaches for individuals dealing with this challenging condition.

Materials and Methods

Study Design and Patients

We performed a retrospective single-center observational analysis to investigate the efficacy of tofacitinib for patients with LPP at a tertiary referral center. This research was approved by the institutional ethical board. After obtaining informed consent from the patients, we reviewed the records of 74 patients with extensive and treatment-resistant LPP who were referred to our dermatology clinic.

For efficacy evaluation, patients with biopsy-confirmed LPP were included in the study. The sample size was determined based on the availability of eligible patients during the study period. As LPP is a rare condition, identifying a larger cohort was not feasible. Comparable studies examining the use of tofacitinib in autoimmune dermatological conditions, such as alopecia areata and other lichen planus subtypes, typically include sample sizes of 30–100 patients. These benchmarks guided our decision, ensuring the study remained practical while providing meaningful insights. Although formal power calculations were not performed due to the retrospective nature of this study, the significant reduction in the LPP Activity Index (LPPAI) observed in our cohort indicates the adequacy of the sample size.

We excluded patients aged under 18 years and over 55 years, those with concurrent alopecia areata, active malignancy or history of malignancy in the past five years, active infection, pregnancy, and lactation, those using systemic medications such as systemic steroids, cyclosporine, hydroxychloroquine, and mycophenolate mofetil in the last three months, those with allergy to tofacitinib or any component of the drug formulation, latent tuberculosis, hepatitis B or C, HIV infection, and those diagnosed with bone marrow suppression (hemoglobin less than 9 g/dL, neutrophils less than 1000 cells/mm³, and lymphocytes less than 500 cells/mm³).

Data Collection

All data on patient demographics were retrieved from patients’ medical records. Data were collected on age, sex, history of accompanying skin disease, history of autoimmune disease, family history of LPP or any autoimmune disease, drugs used in the past for this disease, and the response to previous treatments.

Outcomes and Definitions

The patients underwent treatment with tofacitinib 5 mg twice a day for a minimum of 16 weeks. The dosage of TOF was tapered and then discontinued based on the patient’s condition. The patients were visited monthly and later every two months. Lab test monitoring was performed every two months. After treatment discontinuation, patients were followed up monthly for up to 6 months to assess the recurrence and any potential long-term side effects.

Statistical Analysis

Data analysis was conducted using SPSS version 26.0 (IBM Corp., Armonk, NY, USA). Categorical variables were described with frequencies and percentages, while continuous variables were presented as means ± standard deviations. Normality was evaluated with Shapiro-Wilks test. To compare the LPPAI index before and after the study, Wilcoxon signed rank test was used. A significance level of P< 0.05 was considered in this study.

Results

This study evaluated 74 patients with a mean age of 46.6 ± 8.1 years, of whom 12 (16.2%) were male and 62 (83.8%) were female. The mean age at diagnosis was 42.0 ± 7.9 years, and the mean duration of disease was 55.0 ± 37.5 months.

The median (IQR) LPPAI score before treatment was 5.6 (0.65), which decreased to 2.3 (2.17) at 6 months after treatment (P value = 0.0001). The median difference in LPPAI scores was 3.3 (2.56), reflecting a significant reduction in disease activity. Although 9 (12.2%) patients showed no change in LPPAI after treatment, the overall decrease in the LPPAI score is clinically relevant.

Coexisting Dermatological Diseases

Coexisting dermatological diseases included: eczema: 4 (5.4%), alopecia areata: 3 (4.1%), atopic dermatitis: 6 (8.1%), psoriasis: 3 (4.1%), cutaneous lichen planus: 9 (12.2%), buttock folliculitis: 1 (1.4%), and vitiligo: 1 (1.4%). Medication history of patients included in this study in shown in Table 1.

History of Autoimmune Diseases

Patients had a history of the following autoimmune diseases:

Autoimmune thyroiditis: 17 (23%), diabetes: 2 (2.7%), arthritis: 1 (1.4%).

Family History of Autoimmune Diseases

A family history of autoimmune disease was present in 16 (21.6%) patients, including 15 (20.3%) with a family history of thyroiditis, and one (1.4%) with a family history of lichen planus.

Complications

The complications associated with tofacitinib use were: Headache: 6 (8.1%), hyperlipidemia: 2 (2.7%), elevated liver enzymes: 4 (5.4%), nausea: 5 (6.8%), and high blood pressure: 3 (4.1%). The complications associated with Tofactinib consumption is shown in Table 2.

Response to Treatment

The response rate to tofacitinib was as follows:

• 9 (12.2%) patients did not respond.

• 16 (21.6%) patients responded within 1‒3 months.

• 18 (24.3%) patients responded within 3‒6 months.

• 25 (33.8%) patients responded within 6‒12 months.

• 6 (8.1%) patients responded within 12‒24 months.

Discussion

The effectiveness of tofacitinib treatment in patients with LPP was assessed in this study, revealing a significant improvement in disease activity based on LPPA. The reduction in the average LPPA score from 4.61 ± 1.26 before treatment to 1.73 ± 1.68 six months after treatment was significant (P-value = 0.0001), indicating the efficacy of tofacitinib in treatment of LPP. Our study included 74 patients, predominantly female (83.3%), with a mean age of 46.64 ± 8.05 years. The average age at diagnosis was 42.01 ± 7.95 years, and the average disease duration was 55.04 ± 37.52 months. These demographics are in line with the typical profile of LPP patients, who are often middle-aged women.

The reduction in LPPAI scores aligns with previous studies on tofacitinib, a Janus kinase (JAK1,3) inhibitor, in treating autoimmune skin conditions. For instance, Mackay-Wiggan et al found that tofacitinib effectively treated alopecia areata, another autoimmune condition, with patients experiencing significant hair regrowth and reduced disease activity.¹⁹ Similarly, Craiglow and King reported significant improvements in patients with alopecia universalis treated with tofacitinib.²⁰ The results of our study align with these findings, as 91.84% of our patients experienced a decrease in disease activity, with different response times: 21.62% within 1‒3 months, 24.32% within 3‒6 months, 33.78% within 6‒12 months, and 8.10% within 12‒24 months.

In a case series by Jabbari et al, patients with LPP treated with tofacitinib exhibited significant improvement in both clinical symptoms and histopathological features.²¹ Our study supports these findings by demonstrating a significant reduction in disease activity. Furthermore, Damsky et al documented favorable outcomes in patients with various inflammatory skin conditions who were treated with tofacitinib, emphasizing its potential in the management of autoimmune skin disorders.²² Improvement of patients’ conditions in these studies highlights tofacitinib’s efficacy in treating disorders with pathophysiological mechanisms similar to LPP.

The presence of comorbid dermatological conditions (e.g. eczema, alopecia areata, atopic dermatitis, psoriasis, cutaneous lichen planus) and autoimmune diseases (e.g. autoimmune thyroiditis, diabetes, arthritis) in our study is notable. A significant subset of patients (27%) had these comorbidities, highlighting the complexity of LPP and the need for screening for other autoimmune disorders. Papp et al also highlighted the importance of monitoring these comorbidities, particularly in patients with underlying health conditions.²³

In our study, tofacitinib demonstrated generally mild to moderate adverse effects, including headache (8.10%), hyperlipidemia (2.70%), elevated liver enzymes (5.40%), nausea (6.75%), and high blood pressure (4.15%). Interestingly, female patients exhibited a higher incidence of these side effects, suggesting potential gender-specific responses that warrant further investigation. These findings align with previous research; for instance, studies have reported similar adverse effects in rheumatoid arthritis patients treated with tofacitinib.²⁴ Sandborn et al²⁵ and Papp et al²⁶ also underscored the need for monitoring liver function and lipid levels in patients with ulcerative colitis and plaque psoriasis, respectively. Additionally, our study found that patients previously treated with cyclosporine expressed satisfaction but switched to tofacitinib due to cyclosporine-associated complications like hypertension. This transition highlights the need to balance effectiveness and safety in long-term treatment plans for chronic conditions. Notably, one patient who was not satisfied with tofacitinib after six months was prescribed baricitinib, which led to a satisfactory outcome.²⁷

While this study provides valuable insights into the efficacy of tofacitinib for treating LPP, several limitations inherent in the study design should be considered. One significant limitation is the before-after design. This type of observational design lacks a control group, making it difficult to definitively attribute the observed improvements in disease activity solely to the treatment. Without a comparator group, there is a risk of regression to the mean.

Additionally, the study does not account for time trends that may influence disease progression or treatment outcomes. We acknowledge that external factors that may have changed during the study period could confound the outcome. These limitations highlight the need for further investigations to validate the results. Future research should focus on identifying predictors of response to tofacitinib, exploring the long-term safety and efficacy of this treatment, potential long-term side effects, and comparing its effectiveness with other therapeutic options. Additionally, studies investigating the mechanisms underlying gender differences in adverse effects could provide valuable insights for optimizing patient management.

Conclusion

In conclusion, tofacitinib represents a promising treatment option for LPP, offering significant improvement in disease activity for the majority of patients. However, the variability in response and the incidence of adverse effects necessitate a personalized approach to treatment and accurate monitoring to ensure optimal outcomes.

References

1. Miteva M. Lichen planopilaris. In: Hair Pathology with Trichoscopic Correlations. CRC Press; 2021. p. 89-97.
2. Ruiz-Lozano RE, Hernández-Camarena JC, Valdez-Garcia JE, Roman-Zamudio M, Herrera-Rodriguez MI, Andrade-Carrillo D. Ocular involvement and complications of lichen planus, lichen planus pigmentosus, and lichen planopilaris: a comprehensive review. Dermatol Ther 2021; 34(6):e15137. doi: 10.1111/dth.15137 [Crossref] [ Google Scholar]
3. Babahosseini H, Tavakolpour S, Mahmoudi H, Balighi K, Teimourpour A, Ghodsi SZ. Lichen planopilaris: retrospective study on the characteristics and treatment of 291 patients. J Dermatolog Treat 2019; 30(6):598-604. doi: 10.1080/09546634.2018.1542480 [Crossref] [ Google Scholar]
4. Assouly P, Reygagne P. Lichen planopilaris: update on diagnosis and treatment. Semin Cutan Med Surg 2009; 28(1):3-10. doi: 10.1016/j.sder.2008.12.006 [Crossref] [ Google Scholar]
5. Trager MH, Lavian J, Lee EY, Gary D, Jenkins F, Christiano AM. Prevalence estimates for lichen planopilaris and frontal fibrosing alopecia in a New York City health care system. J Am Acad Dermatol 2021; 84(4):1166-9. doi: 10.1016/j.jaad.2020.10.081 [Crossref] [ Google Scholar]
6. Araghi F, Beyki F, Rakhshan A, Moravvej Farshi H. Generalized lichen planus pigmentosus and a new management approach. Clin Case Rep 2024; 12(6):e8829. doi: 10.1002/ccr3.8829 [Crossref] [ Google Scholar]
7. Larkin SC, Cantwell HM, Imhof RL, Torgerson RR, Tolkachjov SN. Lichen planopilaris in women: a retrospective review of 232 women seen at Mayo Clinic from 1992 to 2016. Mayo Clin Proc 2020; 95(8):1684-95. doi: 10.1016/j.mayocp.2020.02.028 [Crossref] [ Google Scholar]
8. Svigos K, Yin L, Fried L, Lo Sicco K, Shapiro J. A practical approach to the diagnosis and management of classic lichen planopilaris. Am J Clin Dermatol 2021; 22(5):681-92. doi: 10.1007/s40257-021-00630-7 [Crossref] [ Google Scholar]
9. Moussa A, Bhoyrul B, Asfour L, Kazmi A, Eisman S, Sinclair RD. Treatment of lichen planopilaris with baricitinib: a retrospective study. J Am Acad Dermatol 2022; 87(3):663-6. doi: 10.1016/j.jaad.2022.02.027 [Crossref] [ Google Scholar]
10. Damsky W, Wang A, Olamiju B, Peterson D, Galan A, King B. Treatment of severe lichen planus with the JAK inhibitor tofacitinib. J Allergy Clin Immunol 2020;145(6):1708-10.e2. 10.1016/j.jaci.2020.01.031.
11. Kozlov M, Levit EK, Silvers DN, Brichkov I. Severe esophageal lichen planus treated with tofacitinib. Cutis 2023; 111(3):155-63. doi: 10.12788/cutis.0717 [Crossref] [ Google Scholar]
12. Kassels A, Edwards L, Kraus CN. Treatment of erosive vulvovaginal lichen planus with tofacitinib: a case series. JAAD Case Rep 2023; 40:14-8. doi: 10.1016/j.jdcr.2023.08.001 [Crossref] [ Google Scholar]
13. Wollenhaupt J, Lee EB, Curtis JR, Silverfield J, Terry K, Soma K. Safety and efficacy of tofacitinib for up to 95 years in the treatment of rheumatoid arthritis: final results of a global, open-label, long-term extension study. Arthritis Res Ther 2019; 21(1):89. doi: 10.1186/s13075-019-1866-2 [Crossref] [ Google Scholar]
14. Wollenhaupt J, Silverfield J, Lee EB, Curtis JR, Wood SP, Soma K. Safety and efficacy of tofacitinib, an oral janus kinase inhibitor, for the treatment of rheumatoid arthritis in open-label, longterm extension studies. J Rheumatol 2014; 41(5):837-52. doi: 10.3899/jrheum.130683 [Crossref] [ Google Scholar]
15. Burke KE, Ananthakrishnan AN. Tofacitinib: A Jak of All Trades. Clin Gastroenterol Hepatol 2019; 17(8):1438-40. doi: 10.1016/j.cgh.2018.12.044 [Crossref] [ Google Scholar]
16. Nasimi M, Ansari MS. JAK inhibitors in the treatment of lichen planopilaris. Skin Appendage Disord 2024; 10(1):10-7. doi: 10.1159/000534631 [Crossref] [ Google Scholar]
17. Plante J, Eason C, Snyder A, Elston D. Tofacitinib in the treatment of lichen planopilaris: a retrospective review. J Am Acad Dermatol 2020; 83(5):1487-9. doi: 10.1016/j.jaad.2020.05.104 [Crossref] [ Google Scholar]
18. Sadeghi S, Goodarzi A. Various application of tofacitinib and ruxolitinib (Janus kinase inhibitors) in dermatology and rheumatology: a review of current evidence and future perspective. Dermatol Pract Concept 2022; 12(4):e2022178. doi: 10.5826/dpc.1204a178 [Crossref] [ Google Scholar]
19. Mackay-Wiggan J, Jabbari A, Nguyen N, Cerise JE, Clark C, Ulerio G. Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata. JCI Insight 2016; 1(15):e89790. doi: 10.1172/jci.insight.89790 [Crossref] [ Google Scholar]
20. Craiglow BG, King BA. Killing two birds with one stone: oral tofacitinib reverses alopecia universalis in a patient with plaque psoriasis. J Invest Dermatol 2014; 134(12):2988-90. doi: 10.1038/jid.2014.260 [Crossref] [ Google Scholar]
21. Jabbari A, Dai Z, Xing L, Cerise JE, Ramot Y, Berkun Y. Reversal of alopecia areata following treatment with the JAK1/2 inhibitor baricitinib. EBioMedicine 2015; 2(4):351-5. doi: 10.1016/j.ebiom.2015.02.015 [Crossref] [ Google Scholar]
22. Damsky W, Thakral D, Emeagwali N, Galan A, King B. Tofacitinib treatment and molecular analysis of cutaneous sarcoidosis. N Engl J Med 2018; 379(26):2540-6. doi: 10.1056/NEJMoa1805958 [Crossref] [ Google Scholar]
23. Papp KA, Menter MA, Abe M, Elewski B, Feldman SR, Gottlieb AB. Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: results from two randomized, placebo-controlled, phase III trials. Br J Dermatol 2015; 173(4):949-61. doi: 10.1111/bjd.14018 [Crossref] [ Google Scholar]
24. Curtis JR, Lee EB, Kaplan IV, Kwok K, Geier J, Benda B. Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme. Ann Rheum Dis 2016; 75(5):831-41. doi: 10.1136/annrheumdis-2014-205847 [Crossref] [ Google Scholar]
25. Sandborn WJ, Su C, Sands BE, D’Haens GR, Vermeire S, Schreiber S. Tofacitinib as induction and maintenance therapy for ulcerative colitis. N Engl J Med 2017; 376(18):1723-36. doi: 10.1056/NEJMoa1606910 [Crossref] [ Google Scholar]
26. Papp KA, Krueger JG, Feldman SR, Langley RG, Thaci D, Torii H. Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: long-term efficacy and safety results from 2 randomized phase-III studies and 1 open-label long-term extension study. J Am Acad Dermatol 2016; 74(5):841-50. doi: 10.1016/j.jaad.2016.01.013 [Crossref] [ Google Scholar]
27. Moravvej Farshi H, Araghi F. Could baricitinib treat frontal fibrosing alopecia and facial papules?. J Clin Images Med Case Rep 2024; 5(1):2785. [ Google Scholar]