CHICAGO—In biologic-experienced patients with ulcerative colitis, the Janus kinase inhibitor tofacitinib and the interleukin-12/IL-23 inhibitor ustekinumab achieve similar rates of corticosteroid-free remission by 16 weeks, according to results of a multicenter real-world comparison called TORUS.
However, despite similar rates of corticosteroid-free remission (CFR), primary failure to a biologic and treatment with three or more biologics were associated with a significantly higher rate of poor response to ustekinumab (Stelara, Janssen) but not to tofacitinib (Xeljanz, Pfizer), reported Anthony Buisson, MD, PhD, from the Department of Hepatogastroenterology at the University of Clermont-Ferrand, in France.
To compare the drugs, Dr. Buisson and his co-investigators retrospectively evaluated 289 UC patients who were exposed to at least one anti-TNF agent between January 2019 and June 2022 at 10 participating institutions. For inclusion, patients had to have a partial Mayo score (pMs) of at least 2.
At baseline, patients treated with tofacitinib were significantly more likely to have pancolitis (55.6% vs. 42.4%; P=0.026) and a pMs score of at least 6 (64.5% vs. 50.3%; P=0.016), but the proportion on a steroid (~27%) and proportion on a 5-aminosalicylic acid therapy (~11%) were similar.
Propensity scoring was applied to account for most of these differences, but Dr. Buisson acknowledged the limitations of this approach to generating comparative data. “We performed propensity matching for major characteristics known to affect response, but we could not control for all variables,” said Dr. Buisson, who noted that in addition to prior exposure to anti-TNFs, which was a study entry criterion, approximately 75% of patients in both groups had previously been treated with vedolizumab (Entyvio, Takeda).
When calculated with a propensity score, 37.8% of the 124 patients in the tofacitinib group and 35.6% of the 165 patients in the ustekinumab group met the primary CFR end point at 16 weeks (P=0.75).
“In cases of more severe UC, such as pMs at least 6, the primary end point was reached in about the same proportion of patients treated with tofacitinib or ustekinumab [40.6% vs. 41.5%],” reported Dr. Buisson, who presented the data at Digestive Disease Week 2023 (abstract 14).
When compared by prior biologic experience, CFR rates at 16 weeks were numerically but nonsignificantly lower with tofacitinib than with ustekinumab after failure of a single anti-TNF (43.3% vs. 57.1%; P=0.48) or after failure of two anti-TNFs (20.7% vs. 37.9%; P=0.16) (Table). For those with failure of three or more anti-TNFs, CFR rates were higher with tofacitinib than with ustekinumab (46.7% vs. 23.2%; P=0.047).
| Table. CFR Rates by Prior Biologic Experience | |||
| CFR rate at 16 weeks | Tofacitinib | Ustekinumab | P value |
|---|---|---|---|
| After failure of 1 anti-TNF, % | 43.3 | 57.1 | 0.48 |
| After failure of 2 anti-TNFs, % | 20.7 | 37.9 | 0.16 |
| After failure of 3 or more anti-TNFs, % | 46.7 | 23.2 | 0.047 |
| CFR, corticosteroid-free remission; TNF, tumor necrosis factor. | |||
There were many numerical differences between the two therapies for different variables, but they were neither significant nor consistent. For example, endoscopic remission at 16 weeks in a propensity-based analysis was numerically higher among those treated with tofacitinib (17.0% vs. 11.7%; P=0.47), but histologic remission was numerically lower (4.4% vs. 7.8%; P=0.32). For those with an elevated C-reactive protein level (>30 mg/L) at baseline, the lower response to tofacitinib (27.2% vs. 33.0%) did not approach significance.
For ustekinumab, the predictors of failure to achieve CFR were male gender (P=0.035), failure of at least three biologics (P=0.013) and prior exposure to tofacitinib (P=0.03). No predictors of failure could be identified for tofacitinib.
Stephen B. Hanauer, MD, a professor of gastroenterology and hepatology at Northwestern University, in Chicago, commented that a retrospective study with propensity matching “provides evidence but not high-level evidence.” He said this study was “more hypothesis-generating” than a reliable test of the relative clinical efficacy of tofacitinib and ustekinumab in UC patients with prior biologic failure.
However, in the absence of randomized trials, he said that these types of studies are not without value, suggesting that clinicians might consider these results when choosing among treatment options, as long as the limitations are recognized.
For the relatively ambitious goal of CFR at 16 weeks in UC patients who have failed prior anti-TNF therapy, the study indicates that slightly more than one-third of patients will respond whether they receive the JAK inhibitor tofacitinib or the IL-12/IL-23 inhibitor ustekinumab. The data suggest that tofacitinib might be a better choice when employed in patients with multiple prior biologic failures.
“We need more data on therapeutic sequencing in ulcerative colitis, and we are looking forward to the STARTER project that is coming soon,” said Dr. Buisson, referring to a prospective analysis designed to evaluate relative efficacy of UC drugs as first-, second- and third-line therapies.
As newer agents enter the marketplace, “we need more comparative studies, [but] these may or may or may not be forthcoming,” said Dr. Hanauer, providing the rationale for pursuing other methods to consider differences between available drugs.
—Ted Bosworth
Dr. Buisson reported financial relationships with AbbVie, Amgen, Arena, Biogen, Celltrion, Ferring, Galapagos, Gut Care, Janssen, Lilly, Merck, Mylan, NexBiome, Pfizer, Roche and Takeda. Dr. Hanauer reported financial relationships with AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Genentech, GlaxoSmithKline, Janssen, Lilly, Novartis, Pfizer, Progenity and Prometheus.
This article is from the June 2023 print issue.