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Patients with treatment-resistant granulomatosis with polyangiitis (GPA) may see improvement with tofacitinib (Xeljanz), results of a small trial suggested.

Among 11 patients for whom at least four previous drugs had failed, seven showed strong responses when put on the oral Janus-associated kinase (JAK) inhibitor, reported Louise Linde, MD, PhD, of Copenhagen University Hospital in Denmark, and colleagues, in the .

Three of the four whom tofacitinib didn't help gave the drug a solid chance: one took it for 7 months and the other two stayed with it nearly 2 years without showing significant improvement, the researchers noted. The fourth developed a pulmonary embolism 2 weeks after initiating tofacitinib, which clinicians thought may have been related to the drug (its about thrombosis risk) and they quickly stopped it.

GPA is one type of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, a group of autoimmune conditions that lead to damaging inflammation in the small vessels. As such, organs including the lungs, eyes, kidney, and skin may be involved. GPA may also produce masses in the eye sockets and lungs. Standard treatment incorporates an immunosuppressant such as cyclophosphamide plus a corticosteroid.

JAK inhibitors have been proven effective in a variety of other autoimmune inflammatory conditions, starting with rheumatoid arthritis. Tofacitinib now has five FDA-approved indications, and it seemed reasonable to believe it might be effective in GPA. Linde and colleagues began the study in May 2020.

Tofacitinib was given at 5 mg twice daily; one patient with joint symptoms also continued with previous methotrexate. Patients taking prednisolone when starting the trial were allowed to remain on it but doses were tapered as symptoms were brought under control. Other immunosuppressants were stopped at baseline.

Ear-nose-throat manifestations were seen in all patients. Several also had lung nodules and saddle-nose.

Most patients had previously been treated with standard drugs such as prednisolone, cyclophosphamide, azathioprine, methotrexate, and rituximab (Rituxan). Notably, none of the patients had tried the complement C5a receptor inhibitor avacopan (Tavneos), which came on the market for ANCA-associated vasculitis while the trial was already underway.

The investigators used the (BVAS3) to track disease activity. Owing to peculiarities in the index's scoring system, two patients had scores of 0 or 1 when starting tofacitinib despite having serious persistent symptoms. The other nine started with scores of 5 to 9. All of the responding patients showed scores of 0-2 at their last follow-up, which was up to 23 months after initiating the drug, and were continuing to take tofacitinib.

Median C-reactive protein (CRP) levels also declined, from 23 mg/L at baseline to 6 mg/L at last follow-up. CRP levels did not exceed 9 mg/L with treatment among the seven responders. Similarly, among eight patients who started the trial with prednisolone, four stopped it entirely and it was reduced to 5 mg/day in two others.

Limitations included the small number of patients and lack of a control group. Additionally, the authors noted, "[s]ince our study was performed in...patients with predominantly granulomatous manifestations, it cannot be considered representative for patients with predominantly vasculitic manifestations." A larger study with a wider range of GPA presentations is warranted, the group said.

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