Thijs Hendrikx

Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study

Objectives To compare efficacy and safety of various doses of tofacitinib, an oral Janus kinase inhibitor, with placebo in patients with active ankylosing spondylitis (AS, radiographic axial spondyloarthritis). Methods In this 16-week (12-week treatment, 4-week washout), phase II, multicentre, dose-ranging trial, adult patients with active AS were randomised (N=51, 52, 52, 52, respectively) to placebo or tofacitinib 2, 5 or 10 mg twice daily. The primary efficacy endpoint was Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) response rate at week 12. Secondary endpoints included objective measures of disease activity, patient-reported outcomes and MRI of sacroiliac joints and spine. Safety was monitored. Results Emax model analysis of the primary endpoint predicted a tofacitinib 10 mg twice daily ASAS20 response rate of 67.4%, 27.3% higher than placebo. Supportive normal approximation analysis demonstrated tofacitinib 5 mg twice daily ASAS20 response rate significantly higher than placebo (80.8% vs 41.2%; p<0.001); tofacitinib 2 and 10 mg twice daily demonstrated greater response rate than placebo (51.9% and 55.8%, respectively; not significant). Secondary endpoints generally demonstrated greater improvements with tofacitinib 5 and 10 mg twice daily than placebo. Objective (including MRI) endpoints demonstrated clear dose response. Adverse events were similar across treatment groups with no unexpected safety findings. Dose-dependent laboratory outcome changes returned close to baseline by week 16. Conclusions Tofacitinib 5 and 10 mg twice daily demonstrated greater clinical efficacy versus placebo in reducing signs, symptoms and objective endpoints of active AS in adult patients with a similar 12-week safety profile as reported in other indications. Trial registration number NCT01786668.

Tofacitinib or Adalimumab versus Placebo for Psoriatic Arthritis.

Background Tofacitinib is an oral Janus kinase inhibitor that is under investigation for the treatment of psoriatic arthritis. We evaluated tofacitinib in patients with active psoriatic arthritis who previously had an inadequate response to conventional synthetic disease‐modifying antirheumatic drugs (DMARDs). Methods In this 12‐month, double‐blind, active‐controlled and placebo‐controlled, phase 3 trial, we randomly assigned patients in a 2:2:2:1:1 ratio to receive one of the following regimens: tofacitinib at a 5‐mg dose taken orally twice daily (107 patients), tofacitinib at a 10‐mg dose taken orally twice daily (104), adalimumab at a 40‐mg dose administered subcutaneously once every 2 weeks (106), placebo with a blinded switch to the 5‐mg tofacitinib dose at 3 months (52), or placebo with a blinded switch to the 10‐mg tofacitinib dose at 3 months (53). Placebo groups were pooled for analyses up to month 3. Primary end points were the proportion of patients who had an American College of Rheumatology 20 (ACR20) response (≥20% improvement from baseline in the number of tender and swollen joints and at least three of five other important domains) at month 3 and the change from baseline in the Health Assessment Questionnaire–Disability Index (HAQ‐DI) score (scores range from 0 to 3, with higher scores indicating greater disability) at month 3. Results ACR20 response rates at month 3 were 50% in the 5‐mg tofacitinib group and 61% in the 10‐mg tofacitinib group, as compared with 33% in the placebo group (P=0.01 for the comparison of the 5‐mg dose with placebo; P<0.001 for the comparison of the 10‐mg dose with placebo); the rate was 52% in the adalimumab group. The mean change in the HAQ‐DI score was ‐0.35 in the 5‐mg tofacitinib group and ‐0.40 in the 10‐mg tofacitinib group, as compared with ‐0.18 in the placebo group (P=0.006 for the comparison of the 5‐mg dose with placebo; P<0.001 for the comparison of the 10‐mg dose with placebo); the score change was ‐0.38 in the adalimumab group. The rate of adverse events through month 12 was 66% in the 5‐mg tofacitinib group, 71% in the 10‐mg tofacitinib group, 72% in the adalimumab group, 69% in the placebo group that switched to the 5‐mg tofacitinib dose, and 64% in the placebo group that switched to the 10‐mg tofacitinib dose. There were four cases of cancer, three serious infections, and four cases of herpes zoster in patients who received tofacitinib during the trial. Conclusions The efficacy of tofacitinib was superior to that of placebo at month 3 in patients with psoriatic arthritis who had previously had an inadequate response to conventional synthetic DMARDs. Adverse events were more frequent with tofacitinib than with placebo. (Funded by Pfizer; OPAL Broaden ClinicalTrials.gov number, NCT01877668.)

Tofacitinib for Psoriatic Arthritis in Patients with an Inadequate Response to TNF Inhibitors

Background Tofacitinib is an oral Janus kinase inhibitor that is under investigation for the treatment of psoriatic arthritis. We evaluated tofacitinib in patients with active psoriatic arthritis who had previously had an inadequate response to tumor necrosis factor (TNF) inhibitors. Methods In this 6‐month randomized, placebo‐controlled, double‐blind, phase 3 trial, we randomly assigned 395 patients, in a 2:2:1:1 ratio, to four regimens: 5 mg of tofacitinib administered orally twice daily (132 patients); 10 mg of tofacitinib twice daily (132 patients); placebo, with a switch to 5 mg of tofacitinib twice daily at 3 months (66 patients); or placebo, with a switch to 10 mg of tofacitinib twice daily at 3 months (65 patients). Data from the patients who received placebo during the first 3 months of the trial were pooled. The primary end points were the percentage of patients who had at least 20% improvement according to the criteria of the American College of Rheumatology (ACR20 response) and the change from baseline score on the Health Assessment Questionnaire–Disability Index (HAQ‐DI; scores range from 0 to 3, with higher scores indicating greater disability) at the month 3 analysis. Results At 3 months, the rates of ACR20 response were 50% with the 5‐mg dose of tofacitinib and 47% with the 10‐mg dose, as compared with 24% with placebo (P<0.001 for both comparisons); the corresponding mean changes from baseline in HAQ‐DI score were ‐0.39 and ‐0.35, as compared with ‐0.14 (P<0.001 for both comparisons). Serious adverse events occurred in 4% of the patients who received the 5‐mg dose of tofacitinib continuously and in 6% who received the 10‐mg dose continuously. Over the course of 6 months, there were four serious infections, three herpes zoster infections, one myocardial infarction, and one ischemic stroke among the patients who received tofacitinib continuously. Elevations of aspartate and alanine aminotransferase concentrations of three or more times the upper limit of the normal range occurred in more patients who received tofacitinib continuously than in patients who received placebo followed by tofacitinib. Conclusions In this trial involving patients with active psoriatic arthritis who had had an inadequate response to TNF inhibitors, tofacitinib was more effective than placebo over 3 months in reducing disease activity. Adverse events were more frequent with tofacitinib than with placebo. (Funded by Pfizer; OPAL Beyond ClinicalTrials.gov number, NCT01882439.)

Efficacy and safety of tofacitinib following inadequate response to conventional synthetic or biological disease-modifying antirheumatic drugs

Objectives Biological disease-modifying antirheumatic drugs (bDMARDs) have shown diminished clinical response following an inadequate response (IR) to ≥1 previous bDMARD. Here, tofacitinib was compared with placebo in patients with an IR to conventional synthetic DMARDs (csDMARDs; bDMARD-naive) and in patients with an IR to bDMARDs (bDMARD-IR). Methods Data were taken from phase II and phase III studies of tofacitinib in patients with rheumatoid arthritis (RA). Patients received tofacitinib 5 or 10 mg twice daily, or placebo, as monotherapy or with background methotrexate or other csDMARDs. Efficacy endpoints and incidence rates of adverse events (AEs) of special interest were assessed. Results 2812 bDMARD-naive and 705 bDMARD-IR patients were analysed. Baseline demographics and disease characteristics were generally similar between treatment groups within subpopulations. Across subpopulations, improvements in efficacy parameters at month 3 were generally significantly greater for both tofacitinib doses versus placebo. Clinical response was numerically greater with bDMARD-naive versus bDMARD-IR patients (overlapping 95% CIs). Rates of safety events of special interest were generally similar between tofacitinib doses and subpopulations; however, patients receiving glucocorticoids had more serious AEs, discontinuations due to AEs, serious infection events and herpes zoster. Numerically greater clinical responses and incidence rates of AEs of special interest were generally reported for tofacitinib 10 mg twice daily versus tofacitinib 5 mg twice daily (overlapping 95% CIs). Conclusions Tofacitinib demonstrated efficacy in both bDMARD-naive and bDMARD-IR patients with RA. Clinical response to tofacitinib was generally numerically greater in bDMARD-naive than bDMARD-IR patients. The safety profile appeared similar between subpopulations. Trial registration numbers (NCT00413660, NCT0050446, NCT00603512, NCT00687193, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385).

THU0178 Relationship Between NK Cell Count and Important Safety Events in Rheumatoid Arthritis Patients Treated with Tofacitinib

Background Tofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). Cytokines (eg interleukin [IL]-2, -4, -7, -15, -21) involved in lymphocyte development, function and homeostasis are known to signal through JAK. Objectives To characterise changes in natural killer (NK) cell counts following tofacitinib treatment and evaluate the relationship between NK counts and rates of infection and malignancy. Methods Lymphocyte subset data, enumerated by flow cytometric analyses, were pooled from 3 double-blind, placebo-controlled, Phase 2 (P2) studies (two monotherapy and one background methotrexate [MTX]) in MTX inadequate responders, and from a sub-study of an ongoing long-term extension (LTE) study (study is ongoing; database not locked). RA patients (pts) received tofacitinib (1 to 30 mg twice daily [BID]) or placebo for 6 to 24 weeks in P2 and tofacitinib 5 or 10 mg BID for 22 months (median) in LTE. 928 and 161 pts contributed NK cell data in P2 and LTE, respectively. Correlations between baseline or nadir NK cell count and serious infection (SIE, any infection that requires hospitalisation for treatment or parenteral antimicrobial therapy), herpes zoster (HZ) and malignancy (excluding non-melanoma skin cancer) were assessed by sub-dividing NK cell data into deciles and calculating incidence rate (events/100 pt-years) of adverse events for each decile. Results Following tofacitinib administration, NK cell counts decreased in a dose-dependent manner by Week 2 (Figure 1A). Median NK cells counts returned to baseline 2 to 6 weeks after treatment discontinuation (dc). At the 5 mg BID dose, pts with the largest (>90th percentile) decrease in NK cell counts recovered from ∼70% below baseline to ∼18% by 6 weeks after treatment dc (n=4). The estimated median decrease for 5 mg BID at Week 24 was ∼35%. Cross-sectional analyses in different groups of pts showed similar median NK cell count in the LTE (141 cells/μL) compared to pre-treatment baseline (135 cells/μL). No clear association between baseline or nadir NK cell counts (predominantly collected within first 6 months of treatment) and the incidence of SIE, HZ or malignancy (Figure 1B) was seen over the period of observation (median duration 1.9 years). Conclusions Tofacitinib treatment is associated with a dose-dependent decrease in NK cell counts. No association between baseline or nadir NK cell counts and the incidence of SIE, HZ or malignancy was observed. Long-term lymphocyte subset data are being collected in the ongoing LTE study to confirm these relationships. Acknowledgements Previously presented (van Vollenhoven R et al. Arthritis Rheum 2014; 66(11): S220 abs 508) and reproduced with permission from Arthritis and Rheumatism. All aspects of this work were funded by Pfizer Inc. Editorial support under the direction of the authors was provided by Amanda Pedder, of Complete Medical Communications, and funded by Pfizer Inc. Disclosure of Interest R. F. van Vollenhoven Grant/research support from: Pfizer, Consultant for: Pfizer, Y. Tanaka Consultant for: Abbvie, Chugai, Astellas, Takeda, Santen, Mitsubishi Tanabe, Pfizer, Janssen, Eisai, Daiichi-Sankyo, UCB Japan, GlaxoSmithKline, Bristol-Myers Squibb, Speakers bureau: Abbvie, Chugai, Astellas, Takeda, Santen, Mitsubishi Tanabe, Pfizer, Janssen, Eisai, Daiichi-Sankyo, UCB Japan, GlaxoSmithKline, Bristol-Myers Squibb, M. Lamba Shareholder of: Pfizer, Employee of: Pfizer, M. Collinge Shareholder of: Pfizer, Employee of: Pfizer, T. Hendrikx Employee of: Pfizer, T. Hirose Shareholder of: Pfizer, Employee of: Pfizer Japan, S. Toyoizumi Employee of: Pfizer Japan, A. Hazra Shareholder of: Pfizer, Employee of: Pfizer, S. Krishnaswami Shareholder of: Pfizer, Employee of: Pfizer

Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active ankylosing spondylitis (TORTUGA): results from a randomised, placebo-controlled, phase 2 trial

BACKGROUND At present, biological disease-modifying anti-rheumatic drugs (DMARDs) are the only treatment recommended for patients with ankylosing spondylitis who have not responded to first-line treatment with non-steroidal anti-inflammatory drugs (NSAIDs). The TORTUGA trial investigated the efficacy and safety of filgotinib, an oral selective Janus kinase 1 (JAK1) inhibitor, for the treatment of patients with active ankylosing spondylitis. METHODS In this completed, randomised, double-blind, placebo-controlled, phase 2 trial, we enrolled adult patients from 30 sites in seven countries (Belgium, Bulgaria, Czech Republic, Estonia, Poland, Spain, and Ukraine). Eligible patients had active ankylosing spondylitis and an inadequate response or intolerance to two or more NSAIDs. Patients were randomly assigned (1:1) with an interactive web-based response system to receive filgotinib 200 mg or placebo orally once daily for 12 weeks. Randomisation was stratified by current use of conventional synthetic DMARDs and previous receipt of anti-tumour necrosis factor therapy. The patients, study team, and study sponsor were masked to treatment assignment. The primary endpoint was the change from baseline in ankylosing spondylitis disease activity score (ASDAS) at week 12, which was assessed in the full analysis set (ie, all randomised patients who received at least one dose of study drug). Safety was assessed according to actual treatment received. This trial is registered with ClinicalTrials.gov, number NCT03117270. FINDINGS Between March 7, 2017, and July 2, 2018, 263 patients were screened and 116 randomly assigned to filgotinib (n=58) or placebo (n=58). 55 (95%) patients in the filgotinib group and 52 (90%) in the placebo group completed the study; three (5%) patients in the filgotinib group and six (10%) in the placebo group discontinued treatment. The mean ASDAS change from baseline to week 12 was -1·47 (SD 1·04) in the filgotinib group and -0·57 (0·82) in the placebo group, with a least squares mean difference between groups of -0·85 (95% CI -1·17 to -0·53; p<0·0001). Treatment-emergent adverse events were reported in 18 patients in each group, the most common being nasopharyngitis (in two patients in the filgotinib group and in four patients in the placebo group). Treatment-emergent adverse events led to permanent treatment discontinuation in two patients (a case of grade 3 pneumonia in the filgotinib group and of high creatine kinase in the placebo group). No deaths were reported during the study. INTERPRETATION Filgotinib is efficacious and safe for the treatment of patients with active ankylosing spondylitis who have not responded to first-line pharmacological therapy with NSAIDs. Further investigation of filgotinib for ankylosing spondylitis is warranted. FUNDING Galapagos and Gilead Sciences.

The rationale for Janus kinase inhibitors for the treatment of spondyloarthritis

Abstract The pathogenesis of SpA is multifactorial and involves a range of immune cell types and cytokines, many of which utilize Janus kinase (JAK) pathways for signaling. In this review, we summarize the animal and pre-clinical data that have demonstrated the effects of JAK blockade on the underlying molecular mechanisms of SpA and provide a rationale for JAK inhibition for the treatment of SpA. We also review the available clinical trial data evaluating JAK inhibitors tofacitinib, baricitinib, peficitinib, filgotinib and upadacitinib in PsA, AS and related inflammatory diseases, which have demonstrated the efficacy of these agents across a range of SpA-associated disease manifestations. The available clinical trial data, supported by pre-clinical animal model studies demonstrate that JAK inhibition is a promising therapeutic strategy for the treatment of SpA and may offer the potential for improvements in multiple articular and extra-articular disease manifestations of PsA and AS.

Tofacitinib is associated with attainment of the minimally important reduction in axial magnetic resonance imaging inflammation in ankylosing spondylitis patients

Abstract Objectives Minimally important changes (MICs) for SPondyloArthritis Research Consortium of Canada (SPARCC) MRI scores are ⩾2.5 for SI joint and ⩾5 for spine. This post hoc analysis assessed achievement of MIC in SPARCC scores in biologic-naïve patients with AS treated with tofacitinib or placebo, and correlation with clinical responses. Methods Adult AS patients in a 12-week phase 2 study (n = 207) were randomized 1: 1: 1: 1 to tofacitinib 2, 5 or 10 mg twice daily (BID) or placebo. MIC in SPARCC SI joint and spine scores were assessed for patients with available MRI data (N = 164; 79%). Clinical endpoints at week 12, including Assessment of SpondyloArthritis international Society 20% improvement (ASAS20), were compared between patients achieving/not achieving MIC. Results A greater proportion of patients achieved MIC with tofacitinib 2, 5 and 10 mg BID vs placebo for SI joint (28.6, 38.6, 29.6 vs 11.8%) and spine scores (29.3, 36.4, 40.9 vs 11.8%). Generally, a greater proportion of patients treated with tofacitinib 2, 5 and 10 mg BID or placebo, respectively, who achieved MIC for SI joint and spine scores achieved ASAS20 (SI joint: 75.0, 88.2, 69.2, 75.0%; spine: 91.7, 85.7, 72.2, 75.0%) vs patients who did not achieve MIC (SI joint: 51.7, 84.0, 58.1, 48.3%; spine: 46.4, 85.7, 53.8, 48.3%). Numerically greater responses were seen in those patients achieving vs not achieving MIC across a range of other efficacy assessments. Conclusion Approximately one-third of tofacitinib-treated AS patients experienced clinically meaningful reductions in spinal MRI inflammation at week 12. Patients achieving MIC for MRI inflammation had greater clinical response.

Integrated Efficacy Analysis of Tofacitinib, an Oral Janus Kinase Inhibitor, in Patients with Active Psoriatic Arthritis

Background Tofacitinib is an oral Janus kinase inhibitor under investigation for treatment of psoriatic arthritis (PsA). Objectives To determine efficacy based on pooled data from 2 pivotal Phase 3 studies of tofacitinib in patients (pts) with active PsA. Methods Data were pooled from 2 placebo (PBO)-controlled, double-blind, multicentre, global Phase 3 studies (OPAL Broaden [N=422; 12 months; NCT01877668]; OPAL Beyond [N=394; 6 months; NCT01882439]). Pts had active PsA and either inadequate response (IR) to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD) and were tumour necrosis factor inhibitor (TNFi)-naïve (OPAL Broaden), or had IR to ≥1 TNFi (OPAL Beyond). Pts were randomised to tofacitinib 5 mg twice daily (BID), 10 mg BID, adalimumab 40 mg subcutaneous injection once every 2 weeks (OPAL Broaden only) or PBO, in addition to a single, stable background csDMARD. PBO pts advanced to tofacitinib 5 mg or 10 mg BID at Month (M)3. Endpoints included ACR20/50/70 response rates (≥20%, ≥50% and ≥70% improvement), change from baseline (Δ) in HAQ-DI (Health Assessment Questionnaire-Disability Index), HAQ-DI response (decrease from baseline [BL] of ≥0.35), PASI75 (≥75% improvement from BL in Psoriasis Area and Severity Index), ΔLEI (Leeds Enthesitis Index) and enthesitis absence, ΔDSS (Dactylitis Severity Score) and dactylitis absence and ΔDLQI (Dermatology Life Quality Index). Pooled data only included tofacitinib 5 mg and 10 mg BID (to M6) and PBO (to M3). Significance was declared for p≤0.05 without correction for multiplicity. Results For pooled data, pts were predominantly white (94.2%) and female (55.4%) with ≥5 peripheral swollen or tender joints (98.0%), enthesitis (LEI>0; 67.5%), dactylitis (DSS>0; 52.5%), psoriatic body surface area ≥3% (67.7%) and CRP levels above the upper limit of normal (>2.87 mg/L; 62.5%) at BL. Mean age was 49.1 years and PsA duration was 8.0 years. Significant improvements vs PBO at M3 were observed for peripheral arthritis and physical function endpoints for tofacitinib 5 mg and 10 mg BID: ACR20, ACR50, ACR70, ΔHAQ-DI (least squares mean [LSM]), and HAQ-DI response (Table 1). Significant improvements in psoriasis, enthesitis and dactylitis endpoints vs PBO were also observed for tofacitinib 5 mg and 10 mg BID at M3: PASI75, ΔLEI, enthesitis absence based on LEI, ΔDSS (LSM), dactylitis absence based on DSS and ΔDLQI (Table 1). Efficacy was maintained or further improved at M6. Conclusions In a pooled analysis of csDMARD-IR/TNFi-naïve and TNFi-IR pts, tofacitinib 5 mg and 10 mg BID were superior to PBO at M3 across four PsA disease domains: peripheral arthritis, psoriasis, enthesitis and dactylitis. Acknowledgements This study was sponsored by Pfizer Inc. Editorial support was provided by K Haines of CMC and was funded by Pfizer Inc. Disclosure of Interest P. Nash Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer Inc, Roche, UCB, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Merck, Novartis, Pfizer Inc, Sanofi, Roche, UCB, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Novartis, Pfizer Inc, Roche, UCB, L. Coates Speakers bureau: Pfizer Inc, R. Fleischmann Grant/research support from: Abbott, Amgen, Astellas, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Genentech, Eli Lilly, Janssen, Novartis, Pfizer Inc, Regeneron, Sanofi Aventis, Roche, UCB, Consultant for: Abbott, Akros, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Eli Lilly, Janssen, Novartis, Pfizer Inc, Sanofi Aventis, UCB, K. Papp Grant/research support from: Abbott, Amgen, Anacor, Astellas, Celgene, Celtic, Dow Pharma, Eli Lilly, Galderma, Janssen, Janssen Biotech (Centocor), Merck, Novartis, Pfizer Inc, Consultant for: 3M, Abbott, Akros, Alza, Amgen, Astellas, Baxter, Boehringer Ingelheim, Celgene, Cipher, Eli Lilly, Forward Pharma, Funxional Therapeutics, Galderma, Genentech, Isotechnika, Janssen, Janssen Biotech (Centocor), J&J, Kirin, Kyowa, Meiji Seika Pharma, Merck, Mitsubishi Pharma, Mylan, Novartis, Pfizer Inc, Regeneron, Sanofi Aventis, Serono, Stiefel, Takeda, UCB, Speakers bureau: 3M, Abbott, Amgen, Astellas, Boehringer Ingelheim, Celgene, Eli Lilly, Galderma, Janssen, Merck, Novartis, Pfizer Inc, J. Gomez-Reino Grant/research support from: AbbVie, Novartis, Pfizer Inc, Roche, UCB, Consultant for: Pfizer Inc, Speakers bureau: AbbVie, Bristol-Myers Squibb, Janssen, MSD, Pfizer Inc, Roche, UCB, K. Kanik Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Wang: None declared, J. Wu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, T. Hendrikx Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, W. Ports Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

SAT0293 Safety and efficacy of tofacitinib, an oral janus kinase inhibitor, up to 36 months in patients with active psoriatic arthritis: data from the third interim analysis of opal balance, an open-label, long-term extension study

Background Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). Objectives To report the safety, tolerability and efficacy of tofacitinib in patients (pts) with active PsA from an ongoing, open-label, long-term extension (LTE) study (OPAL Balance, NCT01976364; November 2017 data-cut; database not locked). Methods Eligible pts from 2 Phase (P)3 tofacitinib PsA studies (OPAL Broaden, NCT01877668; OPAL Beyond, NCT01882439) entered a 3 year LTE ≤3 months after completing the P3 study or discontinuing for reasons unrelated to study drug. Pts received tofacitinib 5 mg BID to Month (M)1, after which dose adjustments between 5 and 10 mg BID were permitted to improve efficacy, or for safety reasons. Pts receiving a csDMARD at P3 study entry continued the same csDMARD in the LTE. Primary endpoints were incidence and severity of adverse events (AEs) and changes from baseline (Δ) in laboratory values. Safety data are reported up to M36. Efficacy was evaluated up to M30 (when n>50) as a secondary endpoint. Results 686 pts were treated in OPAL Balance; 468 (68.2%) remained in the study at data cut-off. Mean (range) LTE tofacitinib exposure was 614 (1–1032) days. On Day 1, 675 pts (98.4%) received a csDMARD, which was discontinued in 86 pts (12.7%). To M36, 2189 AEs were reported in 546 pts (79.6%), 95 pts (13.8%) had serious AEs and 59 pts (8.6%) discontinued due to AEs. Serious infections occurred in 12 pts (1.7%), herpes zoster (HZ) in 20 pts (2.9%; 1 serious event), major adverse cardiovascular events in 5 pts (0.7%), malignancies in 24 pts (3.5%; including 12 pts with NMSC) and uveitis in 2 pts (0.3%). No AEs of gastrointestinal perforation or inflammatory bowel disease were reported. There were 5 deaths (not attributed to treatment, as assessed by the investigator) due to metastatic pancreatic carcinoma, acute cardiac failure/hypertensive heart disease, chronic obstructive pulmonary disease, pulmonary embolism and cardiovascular insufficiency. Four AEs of latent tuberculosis were reported in pts whose previously negative QuantiFERON response became positive. ALT was elevated ≥3 x ULN in 27 pts (4.0%), and AST≥3 x ULN in 15 pts (2.2%). Changes in laboratory values observed in P3 studies were generally stable in the LTE, except for a modest decrease in absolute lymphocyte count over time. Eight pts (1.2%) discontinued (protocol-mandated) due to laboratory value changes. ACR responses, ΔHAQ-DI, PASI75 response, ΔLeeds Enthesitis Index, ΔDactylitis Severity Score and ΔPain were maintained up to M30. Conclusions Over 36 months in the LTE, the safety profile of tofacitinib in active PsA pts was generally similar to that of the P3 studies. No new safety risks were identified. Efficacy across various PsA disease domains was maintained over time. Acknowledgements Study sponsored by Pfizer Inc. Medical writing support was provided by A MacLachlan of CMC and funded by Pfizer Inc. Disclosure of Interest P. Nash Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant for: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, L. Coates Grant/research support from: AbbVie, Janssen, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, MSD, Novartis, Pfizer Inc, Sun Pharma, UCB, A. Kivitz Consultant for: AbbVie, Celgene, Genentech, Genzyme, Janssen, Merck, Novartis, Pfizer Inc, Sanofi, UCB, Speakers bureau: AbbVie, Celgene, Genentech, Genzyme, Janssen, Merck, Novartis, Pfizer Inc, Sanofi, UCB, P. Mease Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer Inc, Sun, UCB, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer Inc, Sun, UCB, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Novartis, Pfizer Inc, UCB, D. Gladman Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, J. Covarrubias-Cobos Grant/research support from: Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer Inc, D. Fleishaker Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, E. Kudlacz Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Menon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Fallon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, T. Hendrikx Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, K. Kanik Shareholder of: Pfizer Inc, Employee of: Pfizer Inc