Tofacitinib versus ustekinumab as 3rd line treatment in refractory UC

In patients who do not respond to conventional treatments, biotherapies with anti-TNF and anti-integrin (vedolizumab) are the treatments of choice in 1re line for moderate to severe illness. However, a non-negligible percentage of these patients do not respond or subsequently escape these treatments. The recent availability of ustekinumab (anti-IL12/23) and tofacitinib (anti-JAK) in these refractory patients constitutes an alternative to surgery. Today, there are very few objective data to guide clinicians’ choice of one or other of these molecules after failure of anti-TNF and anti-integrin. In this French multicenter cohort, the authors compared in real life, using a propensity score, the effectiveness of these 2 molecules in obtaining clinical remission in patients with ulcerative colitis (UC ) refractory, failure of 2 lines of treatment with anti-TNF and vedolizumab. A total of 93 patients were included in the 4 University Hospitals of the Auvergne-Rhône-Alpes region: 41 received ustekinumab, 52 tofacitinib. The 2 groups were very comparable, particularly in terms of severity of the disease, with an average duration of evolution of UC of 8 years, a majority of pancolic forms, and 41% of corticosteroid-dependent patients (tableau 1).


The 2 treatments are comparable in terms of obtaining clinical remission before statistical adjustment, with remission rates at W8-W12 of 26.6% under ustekinumab and 40.3% under tofacitinib (p = 0.2) , and at W54 by 19.5% and 30.7% (p = 0.2), respectively. Persistence under treatment is on average 11 months under ustekinumab and 12 months under tofacitinib (p = 0.8). There is no significant difference between the 2 treatment groups in terms of recourse to colectomy (7.5%: 5 patients in the ustekinumab group and 2 patients in the tofacitinib group). Age over 60 was associated with ustekinumab treatment; the history of primary non-response to 1st line treatment with biotherapy was associated with treatment with tofacitinib (tableau 2).


These confounding factors explaining 16.9% of the variance were therefore integrated into a logistic regression model. After adjustment, neither treatment was superior to the other in inducing and maintaining clinical remission. Regarding the safety profile, no unexpected adverse effects were reported in this work. In conclusion, this multicenter real-life study confirms that ustekinumab and tofacitinib are 2 valid options in 3rd line biotherapy in refractory UC. Despite the use of a propensity score, it was not possible to establish a difference in terms of clinical remission between these 2 molecules. A trend towards superiority of tofacitinib over ustekinumab was observed, especially in terms of colectomy rate, although this study was not statistically powered to reach significance. The efficacy rates reported in induction for these 2 treatments remain high in these heavily pretreated patients. Colectomy rates are low, suggesting that 3rd line biotherapy is an acceptable alternative to surgery.