What Are Predictors of Sustained Response With Tofacitinib in Ulcerative Colitis?

Patients with ulcerative colitis (UC) who demonstrated a better clinical response to tofacitinib induction therapy after 8 weeks were more likely to maintain response or achieve remission after another 52 weeks, according to findings published in Inflammatory Bowel Diseases.

Researchers conducted a 52-week, randomized, placebo-controlled trial, OCTAVE Sustain (ClinicalTrials.gov Identifier: NCT01458574), enrolling 593 patients with UC who demonstrated a clinical response in 2 identical, 8-week studies (OCTAVE Induction 1 and 2). Patients were randomly assigned to receive 5 mg twice daily of tofacitinib, 10 mg twice daily of tofacitinib, or placebo.

Researchers determined the efficacy of tofacitinib, comparing remission, sustained remission, clinical response, and sustained clinical response at 24 and 52 weeks to baseline measurements.

At the end of the OCTAVE Sustain trial, 170 (34.9%) of the 487 patients achieved remission by week 52, 20.6% achieved sustained remission at weeks 24 and 52, 54.2% achieved clinical response by week 52, and 51.5% achieved sustained clinical response at weeks 24 and 52.

In the 5-mg tofacitinib group, previous failure of tumor necrosis factor inhibitors occurred less frequently in patients who achieved remission, sustained remission, clinical response, or sustained clinical response by week 52, compared with those who failed to achieve these 4 outcomes (29.4% vs 46.5%, 34.1% vs 42.3%, 36.3% vs 44.8%, 36.1% vs 44.4%, respectively).

Patients treated with 5 mg tofacitinib who achieved remission, sustained remission, clinical response, or sustained clinical response at week 52 were less likely to use oral corticosteroids compared with those who did not (42.6% vs 59.4%, 36.4% vs 56.2%, 41.2% vs 70.1%, and 41.2% vs 66.7%, respectively).

Patients who used oral corticosteroids (odds ratios [OR], 0.63; 95% CI, 0.42-0.96) and had higher levels of C-reactive protein (CRP) (OR, 0.94; 95% CI, 0.89-0.99) at baseline demonstrated decreased likelihood of achieving remission after 52 weeks.

At baseline, patients with UC with partial Mayo scores (PMS) less than 2 (OR, 1.92; 95% CI, 1.27-2.90), older age (per every 10 years; OR, 1.19; 95% CI, 1.02-1.39), and lower endoscopic subscores after OCTAVE 1 and 2 (2 vs 3; OR, 1.60; 95% CI, 1.06-2.44) demonstrated increased likelihood of achieving remission after 52 weeks.

The researchers observed similar trends in both the 5-mg and 10-mg tofacitinib groups when determining factors at baseline that influenced the efficacy of maintenance therapy.

“Overall, these results suggest that patients with a deeper response to tofacitinib induction therapy are more likely to maintain response or remission compared with patients with more severe UC, regardless of tofacitinib dose received during maintenance,” the study authors wrote. “Therefore, this highlights the importance of a robust response to induction therapy in the treatment of UC.”

Study limitations include lack of measurement of fecal calprotectin levels, inclusion of patients from OCTAVE 1 and 2 who already had achieved clinical response to tofacitinib, and the posthoc analysis design of this trial, which precluded identification of predictors of response to maintenance therapy.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.