# From apremilast to JAK inhibitors—salvage treatment strategies for refractory palmoplantar pustulosis: case series

## TL;DR

This study shows that switching to JAK inhibitors after failed apremilast treatment can effectively manage severe palmoplantar pustulosis with good tolerability.

## Contribution

Demonstrates JAK inhibitors as a novel salvage therapy for refractory palmoplantar pustulosis after apremilast failure.

## Key findings

- All nine patients showed significant improvement in PPPASI scores after 12 weeks of tofacitinib treatment.
- Eight patients achieved at least a 50% reduction in PPPASI scores, with no serious adverse events reported.
- Switching to JAK inhibitors after apremilast failure offers a viable and well-tolerated treatment option for refractory PPP.

## Abstract

Palmoplantar pustulosis (PPP) is a chronic inflammatory skin condition characterized primarily by recurrent episodes of blisters and sterile pustules on the palms and soles. It is frequently accompanied by disruption of the skin barrier and intense itching or pain. Currently, there is a lack of standardized treatment protocols for PPP therapy. Traditional first-line therapies primarily include topical corticosteroids, immunosuppressants, and localized phototherapy, which offer limited efficacy and are prone to recurrence. Although apremilast (APR) has been reported for use in refractory PPP, its efficacy varies among individuals. This study aims to explore the value of a rescue therapy strategy switching to JAK inhibitors after APR treatment failure.

This study is a single-center retrospective case series analysis, enrolling a total of 9 patients with refractory PPP who remained unresponsive to conventional therapy and APR (30 mg twice daily). All patients discontinued APR and initiated JAK inhibitor therapy (tofacitinib 5 mg twice daily). Concurrently record patients’ baseline characteristics, including comorbidities, smoking history, prior medications, baseline skin lesion severity (PPPASI score), skin lesion status before tofacitinib use, and adverse reactions during follow-up.

Our nine patients responded exceptionally well to tofacitinib. By the end of 12 weeks of treatment, the PPPASI scores of all nine patients had significantly decreased. Among them, eight patients achieved PPPASI50 (88.9%), and one patient achieved PPPASI75 (11.1%). The smallest reduction in PPPASI score from baseline was 2.4 points, and the largest reduction was 16.4 points. No serious adverse events were reported during treatment and follow-up.

For refractory PPP patients who fail APR therapy, switching to JAK inhibitors serves as an effective rescue treatment strategy, with most patients achieving remission within a short period and demonstrating good tolerability. This approach offers a viable treatment option for PPP that has proven resistant to conventional therapies and phosphodiesterase-4 (PDE4) inhibitors. Still, its long-term efficacy and safety require validation through large-scale prospective studies.