Cyclin E2 induces genomic instability by mechanisms distinct from cyclin E1.

OBJECTIVES

This observational study aimed to evaluate the efficacy and safety of the Janus kinase (JAK) inhibitor tofacitinib in the management of recurrent IgG4-related disease (IgG4-RD).

METHODS

Seven patients admitted to the Rheumatology Department of Peking University People's Hospital were enrolled. All patients met the 2019 American College of Rheumatology (ACR) / European League Against Rheumatism (EULAR) classification criteria for IgG4-RD. Disease recurrence was defined as relapse of previously affected organs or involvement of new organs, accompanied by an IgG4-RD Responder Index (IgG4-RD RI) score ≥2 in any item, with or without re-elevation of serum IgG4 levels. Patients were initiated on tofacitinib 5 mg twice daily, with a concurrent increase in glucocorticoids (GCs) dosage not exceeding 10 mg (prednisone equivalent), concomitant immunosuppressants were either continued or discontinued. Clinical data were recorded at baseline, 1 month, 3 months, and every 3 months thereafter. Disease response was assessed using the IgG4-RD RI, physician global assessment (PGA) and serum IgG4 levels. Treatment responses were categorised as complete response (CR), partial response (PR), or relapse.

RESULTS

Patients were aged 33-70 years (mean disease duration, 45 months, range 18-84 months). Six patients achieved CR, while one experienced relapse. Tofacitinib treatment for 1, 3, and 6 months resulted in a reduction in both IgG4-RD RI scores (p=0.017, p=0.018, p=0.043, respectively) and PGA scores (p=0.017, p=0.018, p=0.042, respectively). Serum IgG4 levels decreased at 3 months (p=0.028) and 6 months (p=0.043). Within 6 months of initiating tofacitinib, four out of seven patients reduced their GC dosage to ≤5 mg/day (prednisone equivalent), and two discontinued GCs during follow-up. Tofacitinib was well tolerated. Only one patient developed mild herpes zoster, and no serious adverse events were reported.

CONCLUSIONS

Tofacitinib is effective and safe for the management of recurrent IgG4-RD, with the additional benefit of reducing GC dependence.