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.

Keywords: C-reactive protein; inflammatory bowel disease; partial Mayo score.

© 2022 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.

Figures

Figure 1.

CRP in patients receiving tofacitinib 10 mg BID in OCTAVE Induction 1 and 2, stratified by whether patients achieved clinical and endoscopic outcomes at specified timepoints (full analysis set, observed case analysis). A, Change from baseline in CRP at induction week 4, by week 8 efficacy endpoints. B, Proportion of patients with CRP 

Figure 2.

PMS in patients receiving tofacitinib 10 mg BID in OCTAVE Induction 1 and 2, stratified by whether patients achieved clinical and endoscopic outcomes at OCTAVE Induction week 8 (full analysis set, observed case analysis). A-D, Change from baseline in PMS at weeks 2 and 4. E, Proportion of patients with PMS 

Figure 3.

PMS in tofacitinib induction nonresponders receiving tofacitinib 10 mg BID, stratified by whether patients achieved clinical and endoscopic outcomes at OCTAVE Induction week 16 (full analysis set, observed case analysis). A, Change in PMS from OCTAVE Induction baseline to week 8. 
B, Change in PMS from OCTAVE Induction week 8 to week 12. Abbreviations: BID, twice daily; N, number of patients in the analysis population; 
PMS, partial Mayo score; SD, standard deviation.

Figure 4.

ROC curves for observed CRP and PMS as predictors of clinical and endoscopic outcomes in patients receiving tofacitinib 10 mg BID: A, at induction week 8; B, at induction week 16 (full analysis set, observed case analysis). AUC values between 0.9 and 1.0 = outstanding predictive value; between 0.8 and 0.9 = excellent predictive value; between 0.7 and 0.8 = acceptable predictive value; >0.5–0.7 = poor predictive value; ≤0.5 = no discrimination.aThe optimal threshold is based on the maximum value of the Youden Index (sensitivity + specificity -1), calculated for all possible threshold values. Abbreviations: AUC, area under the curve; CI, confidence interval; CRP, C-reactive protein; PMS, partial Mayo score; 
ROC, receiver operating characteristic; SE, standard error.