Fecal calprotectin levels, c-reactive protein levels, and partial mayo score as early predictors of clinical and endoscopic outcomes in patients with ulcerative colitis treated with tofacitinib in a phase 2 study

INTRODUCTION:

Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Fecal calprotectin (FCP) levels correlated with clinical and endoscopic outcomes at Week (Wk) 8 in patients (pts) with moderately to severely active UC receiving tofacitinib in a Phase 2 study (1). In these post hoc analyses, we aimed to determine if FCP levels, C-reactive protein (CRP) levels, or partial Mayo score (PMS) can be early predictors of clinical or endoscopic outcomes in a Phase 2, randomized, double-blind, placebo-controlled study (NCT00787202) (2).

METHODS:

FCP levels and PMS at baseline, Wk 2, and Wk 4, and CRP levels at baseline and Wk 4 were analyzed based on whether pts with moderately to severely active UC treated with tofacitinib 10 mg twice daily (BID) had clinical response, clinical remission, mucosal healing, or endoscopic remission at Wk 8. Univariate logistic regression analyses were used to evaluate if FCP levels (log transformed), CRP levels (log transformed), or PMS were associated with each outcome.

RESULTS:

In pts treated with tofacitinib 10 mg BID (N = 28), numerically greater decreases from baseline were observed in FCP levels and PMS at Wks 2 and 4 in pts who achieved clinical response, clinical remission, mucosal healing, and endoscopic remission at Wk 8 vs those who did not. FCP levels at Wk 2 decreased by>50% from baseline in pts who achieved endoscopic remission. Numerically greater decreases from baseline were observed in CRP levels at Wk 4 in pts who achieved clinical response and mucosal healing at Wk 8 vs those who did not (Table 1). In pts treated with tofacitinib 10 mg BID, logistic regression results (shown as odds ratio [95% confidence interval]) showed that PMS at Wk 2 (0.496 [0.288, 0.856]; P=0.0117) and Wk 4 (0.463 [0.251, 0.853]; P=0.0135), and CRP levels at Wk 4 (0.582 [0.342, 0.990]; P=0.0460), were significantly associated with clinical remission at Wk 8, and that PMS at Wk 4 (0.572 [0.345, 0.948]; P=0.0302) was significantly associated with clinical response at Wk 8.

CONCLUSION:

These post hoc analyses of a Phase 2 study showed that decreases as early as Wk 2 in FCP levels and PMS, and as early as Wk 4 in CRP levels, may be predictors of improved clinical and endoscopic outcomes in pts with moderately to severely active UC treated with tofacitinib 10 mg BID, although definitive conclusions cannot be drawn due to low pt numbers.