Prediction of early clinical response in patients receiving tofacitinib in the OCTAVE Induction 1 and 2 studies.

INTRODUCTION: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Outcome prediction based on early treatment response, along with clinical and laboratory variables, would be very useful for clinical practice. The aim of this study was to determine early variables predictive of responder status in patients with UC treated with tofacitinib. METHODS: Data were collected from patients treated with tofacitinib 10 mg twice daily in the OCTAVE Induction 1 and 2 studies (NCT01465763 and NCT01458951). Logistic regression and random forest analyses were performed to determine the power of clinical and/or laboratory variables to predict 2- and 3-point partial Mayo score responder status of patients at Weeks 4 or 8 after baseline. RESULTS: From a complete list of variables measured in OCTAVE Induction 1 and 2, analyses identified partial Mayo score, partial Mayo subscore (stool frequency, rectal bleeding, and Physician Global Assessment), cholesterol level, and C-reactive protein level as sufficient variables to predict responder status. Using these variables at baseline and Week 2 predicted responder status at Week 4 with 84-87% accuracy and Week 8 with 74-79% accuracy. Variables at baseline, Weeks 2 and 4 could predict responder status at Week 8 with 85-87% accuracy. CONCLUSION: Using a limited set of time-dependent variables, statistical and machine learning models enabled early and clinically meaningful predictions of tofacitinib treatment outcomes in patients with moderately to severely active UC.

Efficacy and tolerability of celecoxib and naproxen versus placebo in Hispanic patients with knee osteoarthritis.

BACKGROUND: Celecoxib is an effective treatment for osteoarthritis (OA). However, information on its efficacy and safety profile in different racial/ethnic groups is limited. Noticeable differences among racial groups are found in other disease states, but a thorough investigation of OA is lacking. The objective of this study was to determine if celecoxib 200 mg once daily is as effective as naproxen 500 mg twice daily in the treatment of OA of the knee in Hispanic patients. METHODS: Hispanic patients aged ≥45 years with knee OA were randomized to receive celecoxib 200 mg once daily, naproxen 500 mg twice daily, or placebo for 6 weeks. The primary efficacy variable was the change in Patient's Assessment of Arthritis Pain at 6 weeks compared with baseline. Secondary variables were change in Patient's and Physician's Global Assessments of Arthritis from baseline to week 6/early termination, change in Western Ontario and McMaster Universities OA Index (WOMAC) from baseline to week 6/early termination, change in American Pain Society pain score, Pain Satisfaction Scale, Patient Health Questionnaire (PHQ-9), and measurements of upper gastrointestinal tolerability. RESULTS: In total, 239 patients completed the trial (96 celecoxib, 96 naproxen, 47 placebo). Celecoxib was as effective as naproxen in reducing OA pain (least squares mean change from baseline [standard error] -39.7 [2.7] for celecoxib and -36.9 [2.6] for naproxen). Patient's and Physician's Global Assessments of Arthritis, WOMAC scores, upper gastrointestinal tolerability, Pain Satisfaction Scale, and PHQ-9 showed no statistically significant differences between the celecoxib and naproxen groups. The incidence of adverse events and treatment-related adverse events were similar among the treatment groups. CONCLUSION: Celecoxib 200 mg once daily was as effective as naproxen 500 mg twice daily in the treatment of signs and symptoms of knee OA in Hispanic patients. Celecoxib was shown to be safe and well tolerated in this patient population.

The Efficacy of Continuous Versus Intermittent Celecoxib Treatment in Osteoarthritis Patients with Body Mass Index ≥30 and <30 kg/m(2.).

OBJECTIVE: Characterize the effect of body mass index (BMI) on the efficacy of continuous daily celecoxib treatment compared with intermittent celecoxib treatment. METHODS: Prespecified exploratory analysis of a 24-week, double-blind, parallel-group, randomized, multicenter international study. 858 patients with knee or hip osteoarthritis (OA) were randomized to receive celecoxib 200 mg daily either as continuous or intermittent treatment. Efficacy was measured by Western Ontario and McMaster Universities Arthritis Index (WOMAC) total and subscale scores and the number of flare events. RESULTS: Least squares mean increases (worsening) in WOMAC total scores were significantly less in the continuous treatment group than in the intermittent treatment group in patients with a BMI <30 kg/m(2) (1.33 vs 4.85; p=0.016) and in patients with a BMI ≥30 kg/m(2) (1.84 vs 5.12; p=0.019). There was a greater worsening in patients with a BMI ≥30 kg/m(2) than in those with a BMI <30 kg/m(2) in both the continuous and intermittent groups. Fewer flares were reported in the continuous treatment group than in the intermittent group in patients with a BMI <30 kg/m(2) (0.55 vs 0.88; p<0.0001) and ≥30 kg/m(2) (0.54 vs 0.97; p<0.0001). There were no differences in adverse events in the two BMI groups. CONCLUSIONS: Continuous celecoxib treatment was significantly more efficacious than intermittent use in patients with a BMI <30 kg/m(2) compared with obese patients (≥30 kg/m(2)) as assessed by WOMAC total scores and the number of flares. These data suggest that including weight loss as part of a treatment regimen for obese OA patients could be important.