Tofacitinib Shows Promise in Omalizumab-Resistant CSU, New Case Series Finds

A recent case series evaluated the efficacy and safety of tofacitinib in patients with chronic spontaneous urticaria (CSU) who exhibited an inadequate response to omalizumab, addressing an important therapeutic gap in refractory disease management.¹ Tofacitinib induced rapid symptom improvement in some patients, but variability in response and relapse still remains.

Background

Although second-generation antihistamines and dose escalation remain first-line therapy for CSU, up to 40% of patients remain poorly controlled.² Omalizumab is recommended for antihistamine-refractory CSU, yet approximately 30% of patients fail to achieve adequate disease control, particularly those with autoimmune or non–IgE-mediated disease.³ In this context, Janus kinase (JAK) inhibitors have emerged as a promising alternative due to their ability to broadly suppress inflammatory signaling pathways involved in CSU pathogenesis.

Study Design

The authors conducted a single-center retrospective analysis of 10 adult CSU patients with suboptimal response to omalizumab who were treated with oral tofacitinib at a dose of 5 mg twice daily for up to 24 weeks. All patients had previously failed high-dose antihistamines and had received omalizumab (300 mg monthly) for at least 3 months. The study population included 6 women and 4 men with a mean age of 46.8 years and a mean disease duration of nearly 3 years. Baseline disease activity was moderate to severe, with a median UAS7 score of 21 and a median UCT score of 6.5, indicating poor disease control in the majority of patients.

The primary endpoint was achievement of a UCT score ≥12 at week 12. Secondary endpoints included changes in UAS7 and UCT scores over time and safety outcomes. Disease activity and control were assessed longitudinally at multiple time points up to week 24. Prior to treatment initiation, all patients underwent laboratory screening, including complete blood counts, liver and thyroid function tests, total IgE levels, autoantibody testing, and coagulation studies. Hepatitis B and tuberculosis screening were also performed, as tofacitinib use for urticaria represents off-label therapy in China.

Results

Treatment with tofacitinib resulted in rapid and clinically meaningful improvement in many patients. Median UAS7 scores declined significantly from 21 at baseline to 0 by week 8, with 70% of patients achieving clinical remission (UAS7 ≤6) at that time point. Six patients achieved complete symptom resolution. By week 24, the median UAS7 score increased slightly to 7, with 57.1% of patients maintaining remission, suggesting some variability in long-term disease control. Similarly, UCT scores improved steadily, rising from a median of 6.5 at baseline to 12 at week 8 and continuing to improve through week 24. At week 12, approximately 60% to 67% of patients achieved UCT ≥12, meeting the primary endpoint.

Despite these overall positive trends, treatment responses were heterogeneous. Three patients discontinued tofacitinib early due to perceived poor efficacy or concerns regarding adverse effects. Among patients who initially responded, some experienced partial relapse during longer-term therapy. Notably, patients with lower baseline total IgE levels (<100 IU/mL) appeared more likely to achieve early remission, and several responders had evidence of autoimmune involvement, including positive thyroid peroxidase or antinuclear antibodies. In contrast, 2 patients with positive basophil activation tests demonstrated early improvement followed by loss of disease control, suggesting that tofacitinib may be less effective in pathways dominated by FcεRI-mediated mast cell and basophil degranulation.

Safety outcomes were generally favorable. Mild adverse events occurred in 3 patients, including 2 cases of upper respiratory tract infection and 1 instance of transient liver enzyme elevation that resolved after dose reduction. No serious adverse events, thromboembolic complications, or significant laboratory abnormalities were reported during the observation period.

Further Analysis

In discussion, the authors contextualized their findings within the evolving landscape of CSU therapeutics. Compared with cyclosporine, a traditional option for refractory CSU associated with significant toxicity, tofacitinib may offer a more tolerable oral alternative. Emerging evidence from small case reports and ongoing clinical trials of other JAK inhibitors further supports the relevance of this therapeutic class in CSU, particularly in omalizumab-refractory disease.

Overall, this case series provides preliminary evidence that tofacitinib can induce rapid symptom improvement in a subset of patients with refractory CSU, with manageable safety concerns. However, variability in response and relapse highlights the need for better patient stratification and mechanistic understanding. Larger, prospective, multicenter randomized trials are required to define optimal dosing, duration, predictors of response, and long-term safety, and to clarify the role of JAK inhibition within established CSU treatment algorithms.

References

1. Zhang X, Zhu M, Ye Y. (2026). A Case Series of Tofacitinib Treatment for Chronic Spontaneous Urticaria with Inadequate Response to Omalizumab. Clinical, Cosmetic and Investigational Dermatology, 19, 1–7. https://doi.org/10.2147/CCID.S577418

2. Zuberbier T, Abdul Latiff AH, Abuzakouk M, et al. The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria. Allergy. 2022;77(3):734-766. doi:10.1111/all.15090

3. Kolkhir P, Bonnekoh H, Metz M, Maurer M. Chronic Spontaneous Urticaria: A Review. JAMA. 2024;332(17):1464-1477. doi:10.1001/jama.2024.15568