Introduction
Tofacitinib (TOF) is an effective treatment for ulcerative colitis (UC). However, compared with biologics, it is associated with a higher incidence of herpes zoster and malignant tumors, and it is contraindicated in pregnant women. Therefore, TOF is used in the second line or later for patients with UC in whom remission cannot be induced or maintained by biologics. However, patients might elect to discontinue TOF because of malignant disease or the desire to become pregnant. However, the risk of UC recurrence is high if TOF is discontinued. TOF and ustekinumab (UST) have similar mechanisms of action involving the JAK pathway1). The inflammatory cytokines suppressed by these drugs partially overlap2).
Aims & Methods
The aim of this study was to investigate the efficacy and safety of active switching to UST as an alternative to TOF withdrawal. Four patients were included, and the following patient information was recorded: age, gender, duration of disease, disease severity, steroid resistance/dependence, duration of biologic and TOF use before the active switch, reason for the active switch, observation period after the active switch, remission therapy after the active switch, side effects of UST, and outcomes.
Results
Age at diagnosis (median)(months):35–64(49), Males/Females: 0/4, Disease duration(median)(months):85–227(150),Disease severity: severe/moderate: 0/4, Steroid : resistance/dependence: 0/4.
Table
Duration of biologics and tofacitinib before active switch(months)
|
|
case1：
| IFX（3）→TOF(24)
|
case2：
| IFX(53)→ADA(40)→GLM(2)→Seitai(herbal medicine)(25)
→TOF(20)
|
case3：
| ADA(6)→GLM(22)→VED(4)→TOF(24)
|
case4：
| GLM(3)→TOF（22）
|
Reason for active switch
| malignant disease：3 desire to become pregnant：1
|
Observation period after active switch(median) (months)
| 4-23(14)
|
Maintenence therapy :5ASA/AZA
| 4/0
|
Side effect of UST
| none
|
Outcome: relapse/remission
| 0/4
|
IFX:infliximab,TOF:tofacitinib,ADA:adalimumab,GLM:golimumab,VED:vedlizumab
As illustrated in the Table, TOF was used in the second- to fifth-line setting approximately 2 years before an active switch to UST. Treatment with 5ASA alone to maintain remission was performed in all patients, and no cases of relapse, UST-related side effects, or treatment discontinuation were observed. The pregnant patient is currently progressing with her pregnancy smoothly, and she is scheduled to give birth in July 2023.
Conclusion
For patients who require TOF withdrawal, it is possible to safely and effectively maintain remission via an active switch to UST.
References
1) Feng, Z. et al. Breaking through the therapeutic ceiling of inflammatory bowel disease: Dual-targeted therapies. Biomedicine & Pharmacotherapy 158,2023, 114174
2）Danese, S. et al. JAK inhibition using tofacitinib for inflammatory bowel disease treatment a hub for multiple inflammatory cytokines. Am J Physiol Gastrointest Liver Physiol 310 (3): G155, 2016