Tofacitinib-treated Pts Research Articles

S1023 Assessment of Health-Related Quality of Life and Patient-Reported Outcomes With Tofacitinib Treatment Stratified by Age in Patients From the OCTAVE Ulcerative Colitis Clinical Program

S1023 Assessment of Health-Related Quality of Life and Patient-Reported Outcomes With Tofacitinib Treatment Stratified by Age in Patients From the OCTAVE Ulcerative Colitis Clinical Program

AB0750 Back pain and morning stiffness as mediators of tofacitinib treatment effect on fatigue in patients with ankylosing spondylitis: a mediation analysis

BackgroundFatigue is a prevalent symptom of ankylosing spondylitis (AS)1 and can contribute to higher levels of disease, disability and poor health-related quality of life.2 Back pain and morning stiffness are also commonly reported symptoms.3 Tofacitinib is an oral Janus kinase inhibitor for the treatment of adult patients (pts) with AS. In randomised studies, pts with active AS treated with tofacitinib experienced greater improvements in fatigue, back pain and morning stiffness at Week 12 and 16 of treatment compared with placebo (PBO).4,5 Treatment of these symptoms is a priority for pts with AS and their healthcare providers, however, the mechanisms underlying the interrelationships between fatigue, back pain, morning stiffness and treatment are unclear.ObjectivesTo describe the interrelationships between fatigue, back pain, morning stiffness and tofacitinib treatment in pts with AS, using mediation modelling.MethodsData from Phase 2 (NCT01786668)4 and Phase 3 (NCT03502616)5 studies of pts with active AS treated with tofacitinib 5 mg twice daily (BID) or PBO were used. Mediation modelling, a statistical method to assess the extent to which the effect of an independent variable on a dependent variable is indirect, via identified mediators, or direct, capturing all other (unmeasured) effects, was applied.6,7 The initial model included: treatment as the independent binary variable (tofacitinib 5 mg BID vs PBO); fatigue (measured by Functional Assessment of Chronic Illness Therapy-Fatigue) as the dependent variable; mediators included back pain (measured by total back pain/nocturnal spinal pain [numerical rating scale, 0–10]) and morning stiffness (represented by the mean of Bath Ankylosing Spondylitis Disease Activity Index questions 5 and 6).ResultsPooled data from 370 pts were included in the analysis. The initial model showed that 57.5% (p<0.001) of the tofacitinib treatment effect on fatigue was mediated via back pain and morning stiffness (indirect effect); mediation via morning stiffness alone was 49.7% (p<0.01), and 21.2% (p=0.02) via back pain alone. The effect of treatment attributable to factors other than back pain and morning stiffness (ie, direct effect) was not statistically significant (-28.4%; p=0.33). As a result, the initial model was re-specified to exclude the direct treatment effect on fatigue. In the re-specified model (Figure 1), 44.0% (p<0.0001) of the indirect effect of tofacitinib on fatigue was mediated via back pain and morning stiffness; mediation via morning stiffness alone was 40.0% (p<0.001), and 16.0% (p<0.01) via back pain alone. Analyses of the individual study data gave results generally consistent with those from the pooled data.ConclusionOverall, indirect pathways via morning stiffness accounted for ~84% of the effect of tofacitinib treatment on fatigue: (1) treatment affects morning stiffness, which impacts fatigue; and (2) treatment affects morning stiffness, which affects back pain and, ultimately, back pain affects fatigue. The indirect pathway via back pain alone accounted for ~16% of treatment effect on fatigue. These results suggest that in tofacitinib-treated pts with AS, improvements in fatigue are fully mediated through combined treatment effects on morning stiffness and back pain.

DOP59 Evaluation of the efficacy of tofacitinib as maintenance therapy in patients with Ulcerative Colitis stratified by OCTAVE Sustain baseline endoscopic subscore

Abstract Background Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Efficacy and safety of tofacitinib in patients (pts) with UC were evaluated in two 8-week, Phase 3 induction studies (OCTAVE Induction 1&2), a 52-week, Phase 3 maintenance study (OCTAVE Sustain), and an open-label, long-term extension study. Here, we evaluate tofacitinib efficacy in OCTAVE Sustain (NCT01458574) by baseline Mayo endoscopic subscore (ES). Methods Pts with an OCTAVE Sustain baseline ES of 0 or 1 were included. Proportion of pts achieving efficacy endpoints at Week 52 of OCTAVE Sustain (responders from OCTAVE Induction 1&2; tofacitinib 5 or 10 mg twice daily [BID] or placebo [PBO]) was evaluated in relation to OCTAVE Sustain baseline ES. Using logistic regression, the difference in treatment effect (tofacitinib vs PBO) between baseline ES (0 vs 1) for each efficacy endpoint was assessed. Cox proportional hazards regression was used to model the difference in treatment effect between baseline ES (0 vs 1) for time to treatment failure and loss of response. Results At Week 52 of OCTAVE Sustain, a numerically higher proportion of pts with a baseline ES of 0 achieved remission and endoscopic improvement vs pts with a baseline ES of 1, regardless of tofacitinib dose (Table). Logistic regression analyses showed a larger treatment effect of tofacitinib 5 mg BID at Week 52 in pts with a baseline ES of 0 vs 1 (p=0.0306) for clinical response (Table). Treatment effect of tofacitinib 10 mg BID was not significantly different between baseline ES 0 vs 1 for any endpoint (Table). In tofacitinib 5 mg BID-treated pts, Cox proportional hazards regression showed difference in risk vs PBO to be larger in pts with a baseline ES of 0 vs 1 for treatment failure (p=0.0231) and loss of response (p=0.0209); corresponding differences for 10 mg BID-treated pts were not significant (p=0.9239 and p=0.9613, respectively). Conclusion In general, at Week 52 of OCTAVE Sustain, a higher proportion of tofacitinib-treated pts achieved endpoints with a baseline ES of 0 vs 1. Based on proportions, the treatment effect of tofacitinib 5 mg BID was more evident in pts with a baseline ES of 0 vs 1. This difference in treatment effect related to baseline ES was not observed with tofacitinib 10 mg BID. Baseline ES may be an important factor in predicting outcomes, and suggests that aiming for a deeper remission after induction may allow successful maintenance with tofacitinib 5 mg BID. These analyses were post hoc and limited by the small sample sizes.

S0665 Clostridium difficile Infection in Patients With Ulcerative Colitis Treated With Tofacitinib in the Ulcerative Colitis Program: An Update as of May 2019

INTRODUCTION: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. Patients (pts) with UC are susceptible to C. difficile infection (CDI) (1). In the tofacitinib UC clinical program, previous analyses showed CDI rates among tofacitinib-treated pts to be similar or numerically lower than placebo (PBO)-treated pts and pts treated with immunomodulators and TNFi in a generally comparable claims-based observational cohort (2). Here, we present an updated analysis of CDI in the tofacitinib UC clinical program. METHODS: CDI events were evaluated from 4 randomized, PBO-controlled studies (Phase [P]2 and P3 induction studies [NCT00787202; NCT01465763; NCT01458951]; 1 maintenance P3 study [NCT01458574]) and an ongoing, open-label, long-term extension (OLE) study (NCT01470612). 3 cohorts were analyzed: Induction (P2/P3 induction studies), Maintenance (P3 maintenance study) and Overall (pts receiving tofacitinib 5 or 10 mg twice daily [BID] in P2, P3 or OLE studies; analyzed by pts receiving ≥ 1 dose of tofacitinib and predominant dose [PD; 5 or 10 mg BID based on average daily dose <15 mg or ≥ 15 mg, respectively]; data as of May 2019, database not locked). Proportions and incidence rates (unique pts with events per 100 pt-yrs [PY] of exposure) of CDI were evaluated. All pts underwent CDI screening; a positive test excluded pts from program entry. RESULTS: The Overall Cohort comprised 1,157 pts who received ≥ 1 dose of tofacitinib 5 or 10 mg BID, representing 2,581 PY of tofacitinib exposure and up to 6.8 yrs of treatment. CDI occurred in 3 pts in the Induction Cohort (PBO, n = 1; tofacitinib 10 mg BID, n = 2), 3 pts in the Maintenance Cohort (PBO, n = 3; CDI occurred 68, 81 and 98 days following initiation of PBO) and 9 pts in the Overall Cohort (PD tofacitinib 10 mg BID, n = 9; Table 1). Overall Cohort pts with CDI were mild (n = 4) or moderate (n = 5) in severity; 6 pts continued study treatment without interruption, 1 temporarily discontinued and 2 permanently discontinued. CDI resolved with treatment in 8 pts and CDI was still present in 1 pt at the time of study discontinuation. Two events were reported as serious AEs due to hospitalization. CONCLUSION: In the tofacitinib UC program, CDI rates among pts receiving tofacitinib have remained stable since the previous data cut (2) and are comparable to those reported for other advanced therapies (3).Table 1

THU0196 TOFACITINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS AND INDICATIVE OF DEPRESSION AND/OR ANXIETY: A POST HOC ANALYSIS OF PHASE 3 AND PHASE 3B/4 CLINICAL TRIALS

Background:Depression/anxiety are common in RA pts. SF-36 MCS ≤38 can identify probable major depressive disorder and/or probable generalised anxiety disorder (pMDD/pGAD) in RA pts. Tofacitinib is an oral JAK inhibitor for the treatment of RA.Objectives:To assess pMDD/pGAD prevalence in the tofacitinib RA program and efficacy by baseline (BL) pMDD/pGAD status.Methods:Data from pts receiving tofacitinib, ADA, or PBO were pooled from 5 Phase (P)3 and 1 P3b/4 trials. Demographics/BL characteristics were reported by BL pMDD/pGAD (SF-36 MCS ≤38, presence; &gt;38, absence). Month (M)3/6/9/12 SF-36 MCS change from BL (Δ) was estimated, and % with pMDD/pGAD reported. M3/6/12 efficacy outcomes compared tofacitinib-treated pts by BL pMDD/pGAD.Results:BL pMDD/pGAD was seen in 44.5% (tofacitinib 5 mg BID), 39.8% (tofacitinib 10 mg BID), 45.4% (ADA 40 mg Q2W) and 39.1% (PBO) of pts. pMDD/pGAD pts had higher BL CRP and worse disability, fatigue, pain and sleep vs pts without. SF-36 MCS increases were greater for tofacitinib vs PBO/ADA (Fig 1a). The % of pts with BL pMDD/pGAD who continued to have pMDD/pGAD reduced over time, and was generally lower for tofacitinib vs PBO/ADA (Fig 1b). Regardless of BL pMDD/pGAD, efficacy was generally similar for tofacitinib 5 mg BID (Table) and 10 mg BID.Conclusion:~40% of RA pts had BL pMDD/pGAD. SF-36 MCS improvements were greater for tofacitinib vs PBO/ADA. With tofacitinib, % of pts with SF-36 MCS ≤38 reduced by ~60% at M12. Tofacitinib efficacy was similar in pts with/without BL pMDD/pGAD. Limitations include using SF-36 MCS to identify probable rather than confirmed MDD or GAD. Future research using gold standard psychiatric interviews to validate use of SF-36 MCS ≤38 is needed.Table.M3/6/12 efficacy with tofacitinib 5 mg BID, by BL pMDD/pGADaSF-36 MCS ≤38SF-36 MCS &gt;38OR (95% CI)P valueACR20 (%)b,cM355.157.90.89 (0.74, 1.08)0.2330M661.762.80.96 (0.79, 1.16)0.6511M1258.458.60.99 (0.80, 1.22)0.9279ACR50 (%)b,cM325.929.20.85 (0.70, 1.03)0.1022M636.038.00.92 (0.76, 1.11)0.3724M1233.834.30.98 (0.80, 1.20)0.8366ACR70 (%)b,cM310.111.00.91 (0.69, 1.18)0.4704M616.516.51.00 (0.79, 1.26)0.9901M1218.317.51.06 (0.83, 1.34)0.6560DAS28-4(ESR)&lt;2.6 (%)b,cM35.47.40.72 (0.49, 1.05)0.0872M65.98.50.68 (0.49, 0.94)0.0199*M128.011.90.64 (0.47, 0.89)0.0073**ΔHAQ-DI, LS meanc,dSF-36 MCS ≤38SF-36 MCS &gt;38Difference (95% CI)P valueM3-0.41-0.430.01 (-0.04, 0.06)0.6008M6-0.49-0.48-0.01 (-0.06, 0.04)0.6617M12-0.52-0.52-0.01 (-0.06, 0.05)0.8475*p&lt;0.05; **p&lt;0.01 Data pooled from 5 P3 and 1 P3b/4 tofacitinib trialsaBL pMDD/pGAD = SF-36 MCS ≤38;bLogistic regression fit;cFor PBO pts advancing to tofacitinib post-M3, only PBO data were included;dMixed-effects linear model fitΔ, change from baseline; ACR, American College of Rheumatology; BID, twice daily; BL, baseline; CI, confidence interval; DAS28-4(ESR), Disease Activity Score in 28 joints, erythrocyte sedimentation rate; HAQ-DI, Health Assessment Questionnaire-Disability Index; LS, least squares; M, month; MCS, Mental Component Summary score; OR, odds ratio; P, Phase; pGAD, probable generalised anxiety disorder; PBO, placebo; pMDD, probable major depressive disorder; pt, patient; RA, rheumatoid arthritis; SF-36, Short Form-36 health surveyAcknowledgments:Study sponsored by Pfizer Inc. Medical writing support was provided by Sarah Piggott of CMC Connect and funded by Pfizer Inc.Disclosure of Interests:Gustavo Citera Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Rakesh Jain Grant/research support from: Allergan, Eli Lilly, Lundbeck, Otsuka, Pfizer Inc, Shire and Takeda, Consultant of: Acadia, Alfasigma, Allergan, Eisai, Eli Lilly, Evidera, Impel, Janssen, Lundbeck, Merck, Neos Therapeutics, Neurocrine Biosciences, Osmotica, Otsuka, Pamlab, Pfizer Inc, Shire, Sunovion, Supernus, Takeda and Teva, Speakers bureau: Alkermes, Allergan, Eli Lilly, Janssen, Lundbeck, Merck, Neos Therapeutics, Neurocrine, Otsuka, Pamlab, Pfizer Inc, Shire, Sunovion, Takeda, Teva and Tris Pharmaceuticals, Fedra Irazoque-Palazuelos Consultant of: Bristol-Myers Squibb, Janssen, Pfizer Inc, Roche and UCB, Renato Guzman: None declared, Hugo Madariaga: None declared, David C Gruben Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lisy Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lori Stockert Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ming-Ann Hsu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Karina Santana Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Abbas Ebrahim Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Dario Ponce de Leon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

836 Tofacitinib Efficacy in Patients With Moderate to Severe Ulcerative Colitis: Subgroup Analyses of OCTAVE Induction 1 &amp; 2 and OCTAVE Sustain by 5-Aminosalicylates Use

INTRODUCTION: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). The efficacy and safety of tofacitinib were demonstrated in 3 Phase 3 trials (OCTAVE Induction 1 &amp; 2, NCT01465763 &amp; NCT01458951; OCTAVE Sustain, NCT01458574) in patients (pts) with moderate to severe UC (1). In this post-hoc analysis, we explored tofacitinib efficacy for pts with (c5-ASA) and without (n5-ASA) concomitant 5-aminosalicylates use. METHODS: In OCTAVE Induction 1 &amp; 2, pts received placebo (PBO) or tofacitinib 10 mg twice daily (BID) for 8 weeks; clinical responders were re-randomized into OCTAVE Sustain for 52 weeks and received PBO, tofacitinib 5 or 10 mg BID. c5-ASA were permitted at entry, provided doses were stable for ≥4 weeks prior to and during the trials. Remission and mucosal healing were summarized at Week 8 (OCTAVE Induction 1 &amp; 2) and Week 52 (OCTAVE Sustain) by c5-ASA status. Generalized linear models were used to compare adjusted treatment effects between 5-ASA subgroups (Tables 1 and 2). RESULTS: A smaller proportion of c5-ASA pts had prior tumor necrosis factor inhibitor (TNFi) and immunosuppressant failure versus n5-ASA pts, at baseline of OCTAVE Induction and OCTAVE Sustain (OCTAVE Induction 1 &amp; 2: TNFi failure, 42.7% vs 74.5%; immunosuppressant failure, 69.4% vs 78.3%; OCTAVE Sustain: TNFi failure, 36% vs 70%; immunosuppressant failure, 67.9% vs 80%). For both the 5-ASA subgroups, a higher proportion of tofacitinib-treated pts achieved efficacy endpoints, versus PBO-treated pts, at Week 8 of OCTAVE Induction 1 &amp; 2 and Week 52 of OCTAVE Sustain (Tables 1 and 2). Without controlling for baseline variables, higher treatment effects were observed within the c5-ASA subgroup versus the n5-ASA subgroup. When controlled for prior TNFi and immunosuppressant failure (and baseline remission status in OCTAVE Sustain), the differences were not statistically significant in treatment effects between the 5-ASA subgroups in terms of adjusted odds ratios (Tables 1 and 2). CONCLUSION: When controlling for prior UC treatment status, efficacy of tofacitinib, based on adjusted odds ratios, was similar regardless of 5-ASA status. These post-hoc analyses were not intended to evaluate incremental benefit of 5-ASA as combination therapy for tofacitinib.

671 An Update on the Analysis of Non-Melanoma Skin Cancer in the Tofacitinib Ulcerative Colitis Program

INTRODUCTION: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). We present an updated integrated analysis of non-melanoma skin cancer (NMSC) events in the tofacitinib UC clinical program as of Sep 2018. METHODS: NMSC events were evaluated from 4 randomized, placebo-controlled studies (Phase [P] 2 and P3 induction studies [NCT00787202; NCT01465763; NCT01458951], a maintenance P3 study [NCT01458574]), and an ongoing, open-label, long-term extension (OLE) study (NCT01470612). 1–3 Three cohorts were analyzed: Induction (P2/P3 induction studies); Maintenance (P3 maintenance study); Overall (patients [pts] receiving ≥1 dose of tofacitinib 5 or 10 mg twice daily [BID] in P2, P3, or ongoing OLE studies). For P3 studies, a blinded independent adjudication committee reviewed potential NMSC. Proportions and incidence rates (IRs; unique pts with events per 100 pt-years [PY] of exposure) for NMSC were evaluated. A Cox proportional hazards model was used for risk factor analysis. RESULTS: 1124 pts were evaluated for NMSC (P3 studies only), with 2399 PY of tofacitinib exposure and up to 6.1 years of treatment. NMSC occurred in 2 Induction tofacitinib-treated pts, 1 Maintenance placebo-treated pt (IR 0.97), 3 Maintenance 10 mg BID pts (IR 1.91), and 19 Overall Cohort pts (IR 0.78). 10 pts had squamous cell carcinoma (SCC) and 12 pts had basal cell carcinoma (BCC); 3 pts had both SCC and BCC (Table). No NMSC was metastatic or led to discontinuation. The Overall Cohort showed higher IRs for pts aged ≥50 years vs other subgroups and for pts with prior tumor necrosis factor inhibitor treatment, or prior immunosuppressant use vs those without (Table 1). Prior NMSC (hazard ratio [HR] 10.95; 95% CI 3.72, 32.24; P &lt; 0.0001) and age (HR per 10-year increase 2.10; 95% CI 1.41, 3.13; P = 0.0003) were significant risk factors for NMSC. CONCLUSION: NMSC events were infrequent in the tofacitinib UC program, and were more likely to occur in pts with prior NMSC, and with increasing age – known NMSC risk factors. 4 NMSC IRs were similar to those reported for tofacitinib in rheumatoid arthritis 5 and for biologic UC treatments. 6

Improvement in Physicianʼs Global Assessment Within 2 Weeks in Patients With Ulcerative Colitis Treated With Tofacitinib

Introduction: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). OCTAVE Induction 1 & 2 (NCT01465763 & NCT01458951) were identical, randomized, doubleblind, placebo-controlled Phase 3 trials in adult patients (pts) with moderately to severely active UC who had failed, or were intolerant to, steroids, immunomodulators, or tumor necrosis factor inhibitors [1]. Rapid onset of tofacitinib efficacy with significant improvements in pt-reported symptoms (Mayo stool frequency [SF] and rectal bleeding [RB] subscores) was observed within 3 days [2]. Here, we evaluate the time course of improvement in Physician's Global Assessment (PGA) in pts with UC following induction therapy with tofacitinib. Methods: The Mayo score includes the PGA, which comprises pts' levels of discomfort and overall wellbeing. PGA subscores of pts who received placebo or tofacitinib 10 mg twice daily (BID) for 8 weeks (wks) in OCTAVE Induction 1 & 2 were collected at baseline, and at Wks 2, 4, and 8 of the blinded treatment period. Comparisons between groups were made using stratified Cochran-Mantel-Haenszel chi-square test. Results: 905 pts received tofacitinib 10 mg BID (mean age 41.2 years; 59.2% male) and 234 pts received placebo (mean age 41.1 years; 56.4% male). At baseline, the mean total Mayo score in both the placebo group and the tofacitinib group was 9.0; the mean partial Mayo score (total Mayo score excluding endoscopic subscore) in both groups was 6.4. By Wk 2, 10.3% of pts treated with tofacitinib, compared with 3.4% of placebo-treated pts, achieved a PGA subscore of 0 (p<0.01). Similarly, by Wk 2, significantly more pts treated with tofacitinib vs placebo achieved a PGA subscore of 0 or 1 (41.3% vs 27.4%; p<0.0001). A greater proportion of tofacitinib-treated pts had a reduction of ≥1 PGA point from baseline, compared with placebo pts, at Wk 2 (52.0% vs 37.6%; p<0.0001). From Wk 2 to Wk 8, differences between tofacitinib-treated and placebo-treated pts increased for all three PGA subscores analyzed (p<0.01 for all comparisons). Conclusion: In these two randomized trials in pts with UC, treatment with tofacitinib was associated with a significant improvement in the PGA subscores within 2 wks - continuing through Wk 8 - coinciding with improvements in pt-reported symptoms (SF and RB).734 Figure 1 No Caption available.

Symptomatic Improvement Within 3 Days With Tofacitinib Induction Therapy in Patients With Ulcerative Colitis: Results From OCTAVE Induction 1 and 2

Introduction: Tofacitinib is an oral, small molecule JAK inhibitor that is being investigated for ulcerative colitis (UC). Two Phase (P) 3 UC induction trials demonstrated the efficacy of tofacitinib 10 mg twice daily (BID) at Week 2 in partial Mayo score (PMS).1 We evaluated the onset of symptomatic improvement in a post-hoc analysis of diary data. Methods: OCTAVE Induction 1 (NCT01465763) & 2 (NCT01458951) were identical, randomized, placebo-controlled P3 trials in adult patients (pts) with moderately to severely active UC who had failed or were intolerant to steroids, immunomodulators, or tumor necrosis factor inhibitors. Pts received placebo (N=234) or tofacitinib 10 mg BID (N=905) for 8 weeks. Pooled data for OCTAVE Induction 1 & 2 are presented. At screening, pts electronically recorded their normal number of stools per day. During the study, pts continued a daily diary recording their number of bowel movements per day and the presence and description of any blood in the stools. Daily Mayo stool frequency (SF) and rectal bleeding (RB) subscores were calculated for each pt (subscore range of 0-3) based on that day's diary data for the first 15 days of therapy. Least squares mean (LSM) changes from baseline in SF and RB subscores were compared using a linear mixed-effects model. Binary endpoints were compared using stratified Cochran-Mantel-Haenszel chi-square test based on observed data. Results: At baseline for both the placebo and tofacitinib groups, mean SF Mayo subscore was 2.5 and mean RB Mayo subscore was 1.6. Significant improvements from baseline were observed with tofacitinib vs placebo at Day 3 for SF and RB subscores, and were maintained through to Day 15 (Figure). At Day 15, LSM changes from baseline for SF and RB subscores with tofacitinib were -0.74 and -0.76, respectively, vs -0.35 and -0.44, respectively, with placebo (P < 0.0001). At Day 15, 14.6% of tofacitinib-treated pts had an SF score of 0 vs 8.0% with placebo (P < 0.01), and 41.2% of tofacitinib-treated pts had an RB subscore of 0 vs 21.1% with placebo (P < 0.0001).FigureConclusion: In these two P3 induction studies of tofacitinib for pts with moderately to severely active UC, significant symptomatic improvements were observed with tofacitinib vs placebo as early as Day 3. These results support rapid onset of tofacitinib efficacy previously reported based on improvement in PMS.1 Funded by Pfizer Inc.

OP0253 The JAK Inhibitor Tofacitinib Suppresses Synovial JAK1-STAT1 Signalling in Rheumatoid Arthritis

BackgroundTofacitinib is a novel oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). The specific JAK-STAT (signal transducer and activator of transcription) pathways affected by tofacitinib and...

THU0140 Tofacitinib (CP-690,550), an oral janus kinase inhibitor: Analysis of gastrointestinal adverse events across the rheumatoid arthritis clinical programme

BackgroundTofacitinib (CP-690,550) is a novel, oral Janus kinase inhibitor being investigated as a targeted immunomodulator in rheumatoid arthritis (RA).ObjectivesTo describe and report the incidence of gastrointestinal (GI) adverse events (AEs)...

THU0238 Tofacitinib, an Oral Janus Kinase Inhibitor: Safety Comparison in Patients with Rheumatoid Arthritis and an Inadequate Response to Nonbiologic or Biologic Disease-Modifying Anti-Rheumatic Drugs

BackgroundTofacitinib is a novel, oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA).ObjectivesThis analysis provides comparative safety data on the incidence of safety events for patients (pts) with...

OP0163 Evaluation of Influenza and Pneumococcal Vaccine Responses in Rheumatoid Arthritis Patients Using Tofacitinib

BackgroundTofacitinib (CP-690,550) is a novel, oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA).ObjectivesTo evaluate effects of tofacitinib alone, and in combination with methotrexate (MTX), on immunogenicity of...