Association of C-reactive Protein and Partial Mayo Score With Response to Tofacitinib Induction Therapy: Results From the Ulcerative Colitis Clinical Program

Abstract

Background Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). These post hoc analyses assessed associations between C-reactive protein (CRP), partial Mayo score (PMS), and efficacy outcomes during tofacitinib induction in UC. Methods Patients received tofacitinib 10 mg twice daily (BID) in an 8-week, phase 2 induction study and 2 identical, 8-week, phase 3 induction studies (OCTAVE Induction 1&2); induction nonresponders (IndNR) received an additional 8 weeks of tofacitinib 10 mg BID in an open-label, long-term extension study. Associations between CRP and PMS, and efficacy outcomes (clinical response, clinical remission, endoscopic improvement, and endoscopic remission) were analyzed using univariate and multivariable logistic regression and receiver operating characteristic curves. Results Changes from baseline in the logarithm of CRP ([log]CRP) and PMS at week 4 were associated with clinical response at week 8 (univariate: per unit, odds ratio [OR], 0.55 [95% confidence interval (CI), 0.48-0.62]; and 0.42 [0.37-0.47], respectively). Among IndNR, change from baseline in PMS at week 8 was associated with clinical response at week 16 (univariate: per unit, OR, 0.59; 95% CI, 0.46-0.75). C-reactive protein at week 4 (area under the curve [AUC] > 0.6) and PMS at weeks 2 and 4 (AUC, > 0.7) generally exhibited predictive value for week 8 efficacy outcomes. Conclusions Patients who achieved clinical response at week 8 had larger decreases in CRP and PMS at week 4 than patients who did not. IndNR who achieved clinical response at week 16 with extended tofacitinib induction had a larger decrease in PMS at week 8 vs those who did not. ClinicalTrials.gov:NCT00787202;NCT01465763;NCT01458951;NCT01470612.

Early change in serum leucine-rich α-2-glycoprotein predicts clinical and endoscopic response in ulcerative colitis

“…17 Although literature suggests that CRP may not be sensitive enough to detect endoscopic activity in the quiescent disease, it was accurate in detecting response to therapy at week 1 in our study enrolling the moderately to severely active UC. Consistent with our results, it has been reported that CRP at weeks 2-4 predicted induction outcomes by IFX 7 or tofacitinib, 29 and CRP at day 3 was a predictor of colectomy in 30 days in acute severe UC treated with steroids. 30 Surgery or switching to other drugs is recommended if there is no improvement in 1 week in acute severe UC, 31 although such a decision making can be challenging especially when patients show marginal change.…”

Real-World Evidence of Tofacinitib in Ulcerative Colitis: Short-Term and Long-Term Effectiveness and Safety

“…These findings agreed with those described by Honap et al (21) who observed that younger age at treatment initiation and elevated CRP at baseline were independently associated with primary nonresponse. These findings are in line with those previously described in clinical trials, where both CRP and PMS at baseline were associated with short-term response, confirming that patients with higher inflammatory burden are at a higher risk of treatment failure (27). On the contrary, in OCTAVE 1 and 2 trials, the treatment effect was similar between those who had received previous treatment with an anti-TNF agent and those who had not (12).…”

Predictors of Efficacy of Janus Kinase Inhibitors in Patients Affected by Ulcerative Colitis

“…Post hoc analyses of the OCTAVE trials [30] have identified potential predictors of response to tofacitinib [51][52][53][54].…”

“…A more recent post hoc analysis of the OCTAVE induction studies [52] showed that CRP drop and PMS reduction at week 4 were associated with better outcomes in terms of clinical response (per unit odds ratio (OR) 0.86, 95% CI, 0.77-0.97, p = 0.0147, and OR 0.51, 95% CI 0.46-0.57, p < 0.0001, respectively), clinical remission (per unit OR 0.78, 95% CI, 0.67-0.91, p = 0.0020, and OR 0.46, 95% CI 0.40-0.54, p < 0.0001, respectively) and endoscopic improvement (per unit OR 0.66, 95% CI, 0.58-0.75, p < 0.0001, and OR 0.66, 95% CI 0.60-0.73, p < 0.0001, respectively) at week 8. CRP but not PMS was also associated with week-8 endoscopic remission (OR 0.62, 95% CI 0.53-0.73, p < 0.0001).…”