Efficacy and safety of tofacitinib in patients with total and universal alopecia- A retrospective evaluation of 69 patients

Introduction

Alopecia areata (AA) is a CD8+/NKG2D+ T-cell-dependent autoimmune disease with an estimated prevalence of 0.22% in the United States. Approximately, 5% of these cases progress to alopecia universalis (AU) or alopecia totalis (AT).^1,2 Both AU and AT are challenging to treat and have a poor prognosis. The Janus kinase (JAK) and signal transducers and activators of transcription (STAT) pathways play a crucial role in the immunopathogenesis of AA.³ Tofacitinib, a JAK 1/3 inhibitor, has recently shown promising results for severe AA and those unresponsive to conventional therapies.^4,5 However, there are limited data on the efficacy and safety of longer-term clinical applications of tofacitinib. Our study aimed to evaluate the efficacy and safety of tofacitinib in Chinese patients with AT and AU.

Methods

We retrospectively analysed data from AT and AU patients treated with tofacitinib from January 2020 to June 2024. All patients received tofacitinib for at least three months and were evaluated every 2-4 months. The Severity of Alopecia Tool (SALT) score was used to assess hair loss pre-treatment and at various intervals during treatment. A SALT score ≤ 20 was considered a significant improvement⁶ and served as the primary endpoint. Secondary endpoints included the percentage change in the SALT score⁴ from baseline at weeks 12, 24, and 36. We also monitored complete remission (CR) rates and adverse events (AEs).

Data analysis and graphing were performed using IBM SPSS Statistics 27 and GraphPad Prism 8.0. Continuous variables were expressed as mean ± standard deviation (SD) or median (interquartile range [IQR]). Comparisons of rates among more than two groups were conducted using the Chi-square test, while comparisons of continuous variables were performed using one-way analysis of variance (ANOVA). Finally, a binary logistic regression model was employed to analyse the factors influencing the efficacy of tofacitinib.

Results

Significant efficacy of tofacitinib and percent change of SALT score at weeks 12, 24, and 36

With a median treatment of 6 months, significant efficacy was achieved in 33 (47.8%) of the 69 patients by the end of the study. We analysed SALT scores at 12, 24, and 36 weeks to track the responses to tofacitinib. At these intervals, significant efficacy was achieved in 15.9%, 45.0%, and 68.2% of patients [Figure 1a]. The efficacies at weeks 24 and 36 were significantly higher than at week 12 (P < 0.001), and week 36 showed a trend toward even better results, though not statistically distinct from week 24 (P = 0.08). The median SALT score for each interval improved by 40%, 60%, and 90%, respectively, with significant differences between the groups [Figure 1b].

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Figure 1a:

Percentage of patients with significant efficacy (SALT score ≤ 20) at weeks 12, 24, and 36. Compared to weeks 12, ***P < 0.001.

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Figure 1b:

Percentage of SALT score change at weeks 12, 24, and 36. Compared to weeks 12, *P < 0.05, **P < 0.01, ***P < 0.05.

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Discussion

Several studies have demonstrated the efficacy of tofacitinib as a monotherapy or combined therapy at a dose of 10 mg/day or higher for moderate to severe AA.^5,7 A recent retrospective study⁸ showed that after 6 months of tofacitinib treatment, 45% of patients achieved a SALT score of S1, and the final CR rate was 33.75%. Our study also found that 45% of patients had a SALT score ≤ 20% after 6-month treatment, though ultimately, only 26.1% achieved CR. This discrepancy may be due to the inclusion of patchy AA or moderate AA in Huang et al.’s study⁸, while our study focused on patients with AT or AU SALT scores ≥ 50, which are considered refractory AA subtypes. Another study⁹, indicated a decrease from baseline SALT score of 84.5 to 48.6 after 9.8 months of continuous treatment with tofacitinib monotherapy in 9 AU patients. In our study, which included 61 (88.4%) AU patients, the baseline median SALT score of 100 was reduced by 66.67% to 30 after 24 weeks of tofacitinib treatment. While our results are encouraging, the potential synergistic effects of systemic or topical corticosteroids in the short or long term should not be ruled out. Furthermore, 72.5% and 68.1% of our study population had hair loss involving the eyebrow and eyelash areas, respectively. Encouragingly, the final results showed that over 70% of patients had achieved complete or near-complete hair regrowth in these areas. Our study indicated that tofacitinib for AT and AU could achieve significant clinical efficacy within 24 weeks, and that effects may be even better at 36 weeks or longer. During the treatment, 36.2% of patients reported AEs They primarily mentioned acneiform rashes and folliculitis, aligning with previous findings.^5,8 These AEs did not lead to the discontinuation of tofacitinib or significantly affect its efficacy.

Our binary logistic risk assessment model revealed that variables such as AA episode duration, age, comorbidities, and concomitant treatments did not significantly impact the AT and AU patients’ response to tofacitinib. This finding differed from a previous study¹⁰, which suggested that a longer duration of AA episodes predicted a poorer response to JAK inhibitors. Our results indicated that the efficacy of tofacitinib was not significantly affected by the chronicity of AA, when considering multiple factors, while shorter treatment duration and younger age of AA onset were identified as predictors of less favourable outcomes. Eight of the 13 non-responders in our study stopped treatment within three months, which was the likely cause of the ineffective outcome. However, consistent with Mateos-Haro M et al. systematic review¹¹ on tofacitinib’s efficacy and tolerability in paediatric AA, we believe that treatment with tofacitinib should not be limited by the age of onset. Timely and sustained treatment is crucial for refractory AA. Meanwhile, it is our duty to truthfully communicate the efficacy of tofacitinib, according to real-world studies, to patients, helping them set accurate psychological expectations and avoid blind optimism.

Limitations

This retrospective study relies on existing records, which may lack accuracy and completeness in patient data. Additionally, some key indicators affecting efficacy were under-monitored and under-recorded, such as tests for complete blood count (CBC), liver and kidney function, and immune/inflammatory markers.

Conclusion

This study demonstrates that tofacitinib represents a potentially effective alternative for AT and AU patients, with response occurring within six months in a high percentage of patients. It also exhibits a good safety profile, which is crucial for the long-term management of these chronic conditions. Furthermore, a younger age of AA onset and a shorter treatment duration may negatively impact the overall efficacy of tofacitinib. In light of these findings, clinicians and patients should be aware that early treatment initiation and longer treatment durations may enhance the efficacy.