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

被引:8
作者
Dubinsky, Marla C. [1 ]
Magro, Fernando [2 ,3 ]
Steinwurz, Flavio [4 ]
Hudesman, David P. [5 ]
Kinnucan, Jami A. [6 ]
Ungaro, Ryan C. [7 ]
Neurath, Markus F. [8 ]
Kulisek, Nicole [9 ]
Paulissen, Jerome [10 ]
Su, Chinyu [9 ]
de Leon, Dario Ponce [11 ]
Regueiro, Miguel [12 ]
机构
[1] Icahn Sch Med Mt Sinai, New York, NY 10029 USA
[2] Univ Porto, Porto, Portugal
[3] Ctr Hosp Sao Joao, Porto, Portugal
[4] Hosp Israelita Albert Einstein, Unit Inflammatory Bowel Dis, Sao Paulo, Brazil
[5] NYU, New York, NY USA
[6] Mayo Clin, Div Gastroenterol & Hepatol, Jacksonville, FL 32224 USA
[7] Icahn Sch Med Mt Sinai, Dr Henry D Janowitz Div Gastroenterol, New York, NY 10029 USA
[8] Univ Erlangen Nurnberg, Univ Hosp, Dept Med, Erlangen, Germany
[9] Pfizer Inc, Collegeville, PA USA
[10] Pfizer Inc, New York, NY USA
[11] Pfizer Inc, Lima, Peru
[12] Cleveland Clin, Dept Gastroenterol Hepatol & Nutr, Cleveland, OH 44106 USA
关键词
C-reactive protein; inflammatory bowel disease; partial Mayo score; JANUS KINASE INHIBITOR; MAINTENANCE THERAPY; FECAL CALPROTECTIN; INFLAMMATION;
D O I
10.1093/ibd/izac061
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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.
引用
收藏
页码:51 / 61
页数:11
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