Wfc Rigby

OP0202 Efficacy and safety of tofacitinib, an oral janus kinase inhibitor, in patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: opal beyond, a randomised, double-blind, placebo-controlled, phase 3 trial

Background Tofacitinib is an oral Janus kinase inhibitor under investigation for treatment of PsA. Objectives Evaluation of efficacy and safety of tofacitinib vs placebo (PBO) in adult patients (pts) with active PsA and an inadequate response (IR) to TNF inhibitors (TNFi). Methods Eligible pts in this 6-month, randomised, PBO-controlled, double-blind, multicentre, Phase 3 study had ≥6 months PsA diagnosis, met CASPAR criteria, had active arthritis (≥3 tender/painful and ≥3 swollen joints) at screening and baseline, active plaque psoriasis at screening and IR to ≥1 TNFi (discontinued due to inadequate efficacy or adverse event [AE]). Pts were randomised 2:2:1:1 to tofacitinib 5 mg twice daily (BID), tofacitinib 10 mg BID or PBO (advancing to tofacitinib 5 or 10 mg BID in a blinded manner at Month [M]3). Ongoing treatment with 1 conventional synthetic DMARD was required. Pts were followed through M6. Primary endpoints were ACR20 response rate and change (Δ) from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at M3. Results Pts were 92.1% white, 55.3% female and mean age was 50.0 years. At baseline, mean swollen and tender/painful joint counts were 22.0 and 11.8 respectively; mean HAQ-DI score was 1.3; 69.8% of pts had LEI >0; 49.2% had Dactylitis Severity Score (DSS) >0. Most patients (62.7%) had ≥3% BSA affected by psoriasis, for whom median PASI score was 7.9. Discontinuation rate at M3 was 7.6%, and 87.6% completed M6. ACR20 response and ΔHAQ-DI significantly improved with both tofacitinib doses vs PBO at M3 (Fig 1A,B) and were maintained to M6 (Fig 1C,D). Tofacitinib 5 mg and 10 mg BID demonstrated superior ACR20 response vs PBO as early as Week 2 (26.7% [p≤0.05] and 28.8% [p≤0.05] vs 13.0%). Secondary endpoints at M3 for tofacitinib 5 mg and 10 mg respectively were: ACR50 response, 29.8% (p≤0.05), 28.0% (p≤0.05); ACR70 response, 16.8% (not significant [NS]), 14.4% (NS); ≥75% improvement of PASI in pts with baseline BSA ≥3% and PASI >0, 21.3% (NS), 43.2% (p<0.0001); ΔLEI and ΔDSS in pts with baseline score >0: ΔLEI, -1.3 (p≤0.05) and -1.3 (p≤0.05) (least squares mean [LSM]); ΔDSS, -5.2 (p≤0.05) and -5.4 (p≤0.05) (LSM). Effects were maintained to M6. Frequency of serious AEs and discontinuations due to AEs was low and similar across treatment groups (Fig 1E). The most common AEs were upper respiratory tract infection (5.3–10.8%), nasopharyngitis (1.5–10.7%) and headache (4.5–9.1%). Conclusions In this study restricted to PsA pts with TNFi-IR, both tofacitinib doses appeared efficacious on musculoskeletal endpoints for treatment of PsA. No new safety risks were identified vs previous studies in other indications. Acknowledgements Previously presented at ACR 2016, to be presented at AAD 2017 and reproduced with permissions. This study was sponsored by Pfizer Inc. Editorial support was provided by AG McCluskey of CMC and was funded by Pfizer Inc. Disclosure of Interest D. Gladman Grant/research support from: Amgen, AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Pfizer Inc, Novartis, UCB, Consultant for: Amgen, AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Pfizer Inc, Novartis, UCB, Speakers bureau: Amgen, AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Pfizer Inc, Novartis, UCB, W. F. Rigby Grant/research support from: Amgen, Pfizer Inc, Roche, Consultant for: Bristol-Meyers Squibb, Eli Lilly, Pfizer Inc, Roche, V. Azevedo Grant/research support from: Bristol-Myers Squibb, GSK, Pfizer Inc, UCB, Consultant for: AbbVie, Bristol-Myers Squibb, Janssen, Merck Novartis, Pfizer Inc, Serono, F. Behrens Grant/research support from: Abbvie, Pfizer Inc, Roche, Chugai, Prophylix, Bioline, Novartis, Consultant for: Abbvie, Pfizer Inc, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Lilly, R. Blanco: None declared, A. Kaszuba Consultant for: Janssen, Eli Lilly, Novartis, E. Kudlacz Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Menon 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

SAT0439 Integrated safety summary of tofacitinib in psoriatic arthritis clinical studies

Background Tofacitinib is an oral Janus kinase inhibitor under investigation for psoriatic arthritis (PsA). Objectives To describe the safety profile of tofacitinib from integrated Phase (P)3 and long-term extension (LTE) studies. Methods Data were analysed for patients (pts) who received ≥1 dose of tofacitinib 5 or 10 mg BID or placebo (PBO), integrated across 2 P3 studies (OPAL Broaden [12 months; NCT01877668]; OPAL Beyond [6 months; NCT01882439]) and 1 LTE study (OPAL Balance [ongoing, database not locked; NCT01976364]). Common adverse events (AEs; occurring in ≥2% of tofacitinib pts in any group) were analysed in the PBO-controlled portion (Months 0–3) of the P3 studies (Cohort 1 [C1]). Serious AEs (SAEs) and discontinuations due to AEs were analysed over 12 months in pts randomised to tofacitinib 5 or 10 mg BID in P3 studies (Cohort 2a [C2a]); pts randomised to PBO were excluded from this analysis. Deaths and AEs of special interest (serious infections [SI], herpes zoster [HZ], opportunistic infections [OI] including HZ, major adverse cardiac events [MACE], malignancies, non-melanoma skin cancer [NMSC]) were evaluated in all tofacitinib-treated pts in the P3 and LTE studies (Cohort 3 [C3]). Incidence rates (IR; pts with events/100 pt-years [PY] and 95% confidence intervals) are reported. Laboratory results will be reported in future publications. Results C1 included 474 tofacitinib- and 236 PBO-treated pts; C2a included 474 tofacitinib-treated pts; and C3 included 783 tofacitinib-treated pts (exposure: 776 PY). Nasopharyngitis (5.9%) and headache (8.5%) were the most commonly reported AEs at Month 3 in pts receiving tofacitinib 5 and 10 mg BID, respectively (Table). In pts randomised to tofacitinib 5 or 10 mg BID, over 12 months (C2a), the IRs for SAEs were 7.92 (4.09, 13.84) and 8.11 (4.19, 14.17), respectively. Discontinuation due to AEs occurred in 11 (4.6%) and 11 (4.7%) pts randomised to tofacitinib 5 and 10 mg BID, respectively, with IRs of 7.16 (3.58, 12.82) and 7.31 (3.65, 13.08), respectively, over 12 months (C2a). Across all tofacitinib-treated pts in the P3 and LTE studies (C3), SIs occurred in 11 pts (1.4%; IR 1.40 [0.70, 2.50]). HZ was reported in 16 pts (2.0%; IR 2.05 [1.17, 3.33]) receiving tofacitinib. All 3 cases of multidermatomal HZ were adjudicated as OIs; these were the only OIs (0.4%; IR 0.38 [0.08, 1.11]). In C3, 2 deaths occurred (0.3%; IR 0.25 [0.03, 0.91]); all were considered unrelated to the study drug. MACE were reported in 3 pts (0.4%; IR 0.38 [0.08, 1.11]), malignancies (excluding NMSC) in 5 pts (0.6%; IR 0.63 [0.21, 1.48]) and NMSC in 4 pts (0.5%; IR 0.51 [0.14, 1.30]). Conclusions Tofacitinib was well tolerated in pts with PsA, with a safety profile consistent to that seen in RA; no new risks were identified. Longer-term follow-up and larger pt populations will provide further information on the safety profile of tofacitinib in pts with PsA. Acknowledgements These studies were sponsored by Pfizer Inc. Editorial support was provided by C Viegelmann of CMC and was funded by Pfizer Inc. Disclosure of Interest G. Burmester Grant/research support from: UCB, Consultant for: AbbVie, Bristol-Myers Squibb, Eli Lilly, Hexal, Janssen, MSD, MedImmune, Novartis, Pfizer Inc, Sanofi, Roche, Speakers bureau: AbbVie, Bristol-Myers Squibb, Hexal, MSD, Novartis, Pfizer Inc, Roche, O. FitzGerald Grant/research support from: AbbVie, Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer Inc, Speakers bureau: Celgene, Janssen, Novartis, K. Winthrop Grant/research support from: Bristol-Myers Squibb, Pfizer Inc, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Galapagos, Pfizer Inc, UCB, G. Williams Consultant for: Pfizer Inc, V. Azevedo Grant/research support from: Bristol-Myers Squibb, GSK, Pfizer Inc, UCB, Consultant for: AbbVie, Bristol-Myers Squibb, Janssen, Merck Novartis, Pfizer Inc, Serono, W. F. Rigby Grant/research support from: Amgen, Pfizer Inc, Roche, Consultant for: Bristol-Myers Squibb, Eli Lilly, Pfizer Inc, Roche, K. Kanik Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, P. Biswas Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, T. Jones Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Menon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, N. Palmetto Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, R. Rojo Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

FRI0110 Assessment of Immunogenicity of Live Zoster Vaccination in Rheumatoid Arthritis Patients on Background Methotrexate before and after Initiating Tofacitinib or Placebo

Background Tofacitinib is an oral JAK inhibitor for the treatment of RA. Clinical guidelines recommend live zoster vaccine (LZV) to prevent shingles in RA, but this has not been studied in RA patients (pts) and the effect of tofacitinib on humoral or cell-mediated responses to LZV is unknown. Objectives To evaluate the effect of tofacitinib upon the immune response (IR) and safety of LZV. Methods Pts were aged ≥50 years with active RA (≥4 tender/painful joints and ≥4 swollen joints) despite methotrexate (MTX) ≥4 months (15–25 mg/wk before screening) (study NCT02147587). Pts with prior history of zoster vaccination were excluded, as were those receiving any vaccine in the 6 wks prior to randomisation. After screening, eligible pts on background MTX received LZV and then either tofacitinib 5 mg BID or placebo (PBO) starting 2–3 wks post-vaccination. Both humoral (varicella-zoster virus [VZV]-specific IgG via gpELISA) and cell-mediated responses (VZV-specific T cell enumeration via ELISPOT) before vaccination (baseline [BL], day of vaccination), and then at 2, 6 and 14 wks post-vaccination were measured. Primary endpoint: geometric mean fold rise (GMFR) in VZV-specific IgG titre at 6 wks post-vaccination. Secondary endpoint: proportion of pts achieving a ≥1.5 fold rise in VZV-specific IgG titre 6 wks post-vaccination. Exploratory endpoint: GMFR in VZV-specific T cells (spot-forming cells/106 peripheral blood mononuclear cells) by ELISPOT between BL and 6 wks post-vaccination. Pts were followed for 12 wks after randomisation for safety. Results 112 pts were randomised to PBO (n=57) and tofacitinib (n=55). Most PBO (93%) and tofacitinib (98%) pts were evaluable for IR endpoints. Pts were similar with regard to sex, age, baseline disease activity and baseline VZV immune measures (i.e. IgG, ELISPOT). The GMFR in VZV-specific IgG titre at 6 wks was 2.11 for tofacitinib and 1.74 for PBO. GMFRs in tofacitinib and PBO pts were comparable with GMFRs in healthy people ≥50 years as indicated in the LZV labels. The proportion of pts with a 1.5 fold rise in IgG titre at 6 wks post-vaccination rise trended higher for tofacitinib (57.4%) vs PBO (43.4%). The VZV-specific T cell GMFR at 6 wks increased similarly for tofacitinib (1.50) and PBO (1.29). SAEs occurred in 0 and 3 (5.5%) of PBO and tofacitinib arms respectively. One pt had cutaneous dissemination with vaccine-strain VZV (Oka strain virus) 2 days after starting tofacitinib (16 days post-vaccination). This pt was found to lack pre-existing immunity to VZV, consistent with vaccine-induced disease. The event resolved after tofacitinib discontinuation and antiviral therapy. Conclusions Pts starting tofacitinib had similar VZV-specific humoral and cell-mediated IRs to LZV as compared to PBO-treated pts. Vaccination appeared safe in pts subsequently treated with tofacitinib; however, one patient who lacked pre-existing VZV immunity developed vaccine-induced disease. Acknowledgement Previously presented (Winthrop K et al. Arthritis Rheumatol 2015; 67 (S10): Abstr 12L) and reproduced with permission. This study was funded by Pfizer Inc. Editorial support was provided by S. Johnson of Complete Medical Communications and funded by Pfizer Inc. Disclosure of Interest K. Winthrop Grant/research support from: BMS, Pfizer Inc, Consultant for: Pfizer Inc, UCB, AbbVie, Lilly, BMS, Galapagos, and Amgen, A. Wouters Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, E. Choy Grant/research support from: Amgen, Boehringer Ingelheim, Chugai Pharma, Ferring Pharmaceuticals, Novimmune, Pfizer Inc, Roche, and UCB, Speakers bureau: Amgen, Boehringer Ingelheim, Chugai Pharma, Eli Lilly, Hospira, MSD, Novartis, Pfizer Inc, Regeneron, Roche, Sanofi-Aventis, and UCB, K. Soma Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Hodge Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Nduaka Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, P. Biswas Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. McNeil Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Passador Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Mojcik Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, W. Rigby Grant/research support from: Amgen, Pfizer Inc and Roche., Consultant for: for Bristol-Myers Squibb, Eli Lilly, Pfizer Inc and Roche

Differential efficacy of TNF-α antagonists in granulomatous diseases: potential explanations

Abstract TNF-α antagonists show differential efficacy in granulomatous disorders. Both infliximab and adalimumab have been shown to be effective in Crohns disease while etanercept lacks efficacy in this disease. Somewhat similar results have been reported with regard to Wegeners granulomatosis and pulmonary sarcoidosis. It is interesting to note that cases of mycobacterium tuberculosis (TB) occur earlier and more frequently in patients with infliximab relative to etanercept. These observations would suggest that infliximab (and possibly adalimumab) is superior to etanercept in blocking granulomatous inflammation. However, no conclusive data are available at present. Three attributes of the TNF antagonists are crucial to understanding the observed differences: mode of administration, the IgG antibody backbone and the nature of TNF-α binding. Infliximab (and presumably, adalimumab) is able to bind transmembrane TNF with greater avidity than etanercept. Besides, the two TNF receptors (p55 and p75) exhibit complex interactions involving the binding of TNF. Also, TNF receptor signalling pathways are mutually influenced by effects of other TNF receptors (e.g. TRAIL, FAS, CD40). It has been shown that p55 TNF receptor conveys both survival and death (apoptotic) signals, while the p75 receptor is thought to mostly convey survival signals, yet plays a clear role in Fas-FasL mediated apoptosis or activation induced cell death. On the basis of results of available studies one can conclude that a) acute administration of infliximab reduces inflammation and cellularity through apoptotic and non-apoptotic pathways, which vary as a function of organ and or disease process, b) chronic administration of infliximab and etanercept can induce macrophage apoptosis and this correlates with clinical response, arguing against a specific role for transmembrane TNF binding in inducing apoptosis, c) either methodologic or organ system differences must account for the differential findings in vitro, and d) although it is likely pharmacokinetics and pharmacodynamics play some role, only studies specifically designed to address these questions will resolve these issues.

OP0035 Upadacitinib as monotherapy: a phase 3 randomised controlled double-blind study in patients with active rheumatoid arthritis and inadequate response to methotrexate

Background Upadacitinib (UPA), an oral JAK inhibitor, showed efficacy in rheumatoid arthritis (RA) patients (pts) with an inadequate response to csDMARDs or bDMARDs on continuing stable csDMARD(s).1 2 Objectives Safety and efficacy of switching to UPA 15u2009mg or 30u2009mg monotherapy vs continuing methotrexate (MTX) as a blinded study drug was evaluated in pts with inadequate response to MTX (MTX-IR). Methods Pts with active RA (TJC ≥6, SJC≥6, hsCRP ≥3u2009mg/L) on stable MTX were enrolled and randomised 1:1:1 in a double-blind manner to once-daily (QD) UPA 15u2009mg or 30u2009mg monotherapy or to continue MTX (cMTX) at their prior stable dose. At BL, all pts discontinued prior MTX without washout and received PBO (for pts on UPA) or MTX at prior dose (cMTX) as blinded study drug. The primary endpoints at Week (Wk) 14 were the proportion of pts achieving ACR20, and the proportion achieving DAS28-CRP≤3.2 (NRI). Results 648 pts were randomised, all received study drug; 598 (92.3%) completed 14 wks. BL demographics and disease characteristics were generally similar across arms. Both primary endpoints were met (p<0.001); at Wk 14, a significantly greater proportion of pts receiving UPA monotherapy (15u2009mg and 30u2009mg) vs cMTX achieved ACR20 (67.7% and 71.2% vs 41.2%), and DAS28-CRP≤3.2 (44.7% and 53.0% vs 19.4%) (table 1). All key secondary endpoints also showed UPA 15 and UPA 30 monotherapy to be superior to cMTX, including ACR50 (41.9% and 52.1% vs 15.3%), ACR70 (22.6% and 33.0% vs 2.8%), DAS28-CRP<2.6 (28.1% and 40.5% vs 8.3%), ΔHAQ-DI (−0.65 and −0.73 vs −0.32). ΔSF-36 PCS and ΔMorning Stiffness data are also shown (table 1). The proportion of pts achieving CDAI≤10 was significantly greater with UPA 15 and 30 vs cMTX (34.6% and 46.5% vs 24.5%). Adverse events (AEs) were reported at similar frequencies across arms; serious AEs were numerically higher in UPA 15 but similar between cMTX and UPA 30 (table 1). Numerically more infections were reported in cMTX and UPA 30 vs UPA 15. One serious infection each was reported in UPA 15 and cMTX, and none in UPA 30. Herpes zoster was more frequent in UPA 30 vs UPA 15 or cMTX. 3 malignancies (1 in cMTX and 2 in UPA 15) and 3 adjudicated MACE (1 in UPA 15 and 2 in UPA 30) were reported. One adjudicated pulmonary embolism was reported (UPA 15) in a pt with known risk factors (BMI 36; on oestrogen therapy). One death (haemorrhagic stroke due to ruptured aneurysm) was reported in UPA 15. No TB, renal dysfunction or GI perforation was reported. Rates and types of laboratory abnormalities were consistent with prior UPA RA studies to date.Abstract OP0035 – Table 1 Conclusions In this MTX-IR study population, switching to UPA as monotherapy at 15u2009mg and 30u2009mg QD showed significant improvements in RA signs and symptoms vs continuing MTX. Numerically higher responses were observed for UPA 30u2009mg vs 15u2009mg, particularly for more stringent efficacy criteria. Safety observations were similar to those in prior UPA studies. References [1] Burmester, et al. Arth Rheum2017;69:S10. [2] Genovese, et al. Arth Rheum2017;69:S10. Acknowledgements AbbVie: Study sponsor, study design, data collection, analysis and interpretation, writing, review, approval of final. Medical writing:Naina Barretto of AbbVie Disclosure of Interest J. Smolen Grant/research support from: AbbVie, Consultant for: AbbVie, S. Cohen Grant/research support from: Abbvie, Gilead, Eli Lilly,Pfizer, Consultant for: Abbvie, Gilead, Eli Lilly,Pfizer, P. Emery Grant/research support from: Pfizer, MSD, AbbVie, Bristol-Myers Squibb, UCB, Roche, Novartis, Samsung, Sandoz and Lilly., Consultant for: Pfizer, MSD, AbbVie, Bristol-Myers Squibb, UCB, Roche, Novartis, Samsung, Sandoz and Lilly., W. Rigby: None declared, Y. Tanaka Grant/research support from: Mitsubishi-Tanabe, Takeda Ltd, BMS, Chugai Ltd, Astellas Inc, AbbVie GK, MSD K.K., Daiichi Sankyo Ltd, Pfizer Japan Inc., Kyowa Hakko Kirin, Ltd, Eisai., Ltd, Ono, Ltd, Speakers bureau: Daiichi Sankyo Ltd, Astellas Pharma Inc, Pfizer Japan Inc., Mitsubishi-Tanabe, BMS, Chugai Ltd, YL Biologics, Eli Lilly Japan KK, Sanofi KK, Janssen KK, UCB Japan, Ltd, Y. Zhang Shareholder of: AbbVie, Employee of: AbbVie, A. Friedman Shareholder of: AbbVie, Employee of: AbbVie, A. Othman Shareholder of: AbbVie, Employee of: AbbVie, H. Camp Shareholder of: AbbVie, Employee of: AbbVie, A. Pangan Shareholder of: AbbVie, Employee of: AbbVie

AB0448 Patient-reported outcomes following discontinuation of methotrexate in patients with rheumatoid arthritis treated with subcutaneous tocilizumab: results from a randomised controlled trial

Background Patients with rheumatoid arthritis (RA) often receive methotrexate (MTX) in combination with biologics; however, MTX may be discontinued due to intolerance or to reduce the medication burden once disease control is achieved. Whereas previous studies have established the efficacy of tocilizumab (TCZ) initiated as monotherapy (MONO) for the treatment of RA,1,2 patient-reported outcomes (PROs) after MTX withdrawal in patients achieving good clinical response to TCZ +MTX have not been evaluated. PROs are important measures when determining response to therapy in patients with RA with respect to health-related quality of life (HRQOL).3,4 Objectives This study evaluated PROs between patients with RA who achieved low disease activity with TCZ +MTXu2009and then continued or discontinued MTX in the COMP-ACT trial (NCT01855789). Methods US patients with RA who were inadequate responders to MTX were enrolled; initial combination therapy included MTX (≥15u2009mg/week orally) plus TCZ 162u2009mg subcutaneous either weekly (qw) or every 2 weeks (q2w). Patients who achieved DAS28-ESR≤3.2 at Week 24 were randomised 1:1 to receive TCZ-MONO or continue TCZ +MTX until week 52 (double-blind). Changes in PRO scores were measured between Week 24 and Weeks 40 and 52, and included patient global assessment of disease activity (PtGA; visual analogue score [VAS], 0–100u2009mm), pain (VAS), Health Assessment Questionnaire Disability Index (HAQ-DI, 0–3) and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue. Results Of the 296 randomised patients (TCZ +MTX, n=148; TCZ-MONO, n=148), 74.8% were women, mean age was 55.5 years, mean RA duration was 6.8 years and mean DAS28-ESR was 6.3 at baseline. At Week 24 (randomization), PRO scores were similar between the randomised treatment groups. The mean changes in PtGA, pain, HAQ-DI and FACIT-fatigue scores from Week 24 to Weeks 40 were similar between the TCZ +MTXu2009and TCZ-MONO groups (table 1). The proportion of patients with HAQ-DI <0.5 was similar between the groups at Week 24 (randomization), and remained similar at Weeks 40 and 52.Abstract AB0448 – Table 1 Changes in Patient-Reported Outcomes from Week 24 (Randomization) to Week 40 and Week 52 FACIT, Functional Assessment of Chronic Illness Therapy; HAQ-DI, Health Assessment Questionnaire Disability Index; MONO, monotherapy; MTX, methotrexate; PtGA, patient global assessment; SEM, standard error of the mean; TCZ, tocilizumab. * A negative change in score represents an improvement in the respective PRO except for Fatigue. † Estimated means from ANCOVA model includes Week 24 value as a covariate, treatment group, and the randomization stratification factors: DAS28 remission status at Week 24 (<2.6,≥2.6u2009to≤3.2), baseline weight-by-dosing group (<80u2009kg every 2 weeks [q2w],<80u2009kg weekly [qw], 80 to <100u2009kg q2w, 80 to <100u2009kg qw,≥100u2009kg qw), patient anti-TNF exposure (Yes or No). Conclusions Patients receiving TCZ who discontinue MTX appear to have similar PROs across multiple measures compared with patients continuing TCZ +MTX. Differences observed in clinical parameters between TCZ-MONO and TCZ +MTX did not appear to achieve a threshold that would be considered clinically meaningful. Similarities in PROs on both treatments were consistent with the clinical efficacy measures previously reported from COMP-ACT. References [1] Jones G, et al. J Rheumatol2017;44(2):142–6. [2] Dougados M, et al. Ann Rheum Dis. 2013;72(1):43–50. [3] Deshpande PR, et al. Perspect Clin Res. 2011;2(4):137–44. [4] Her M, Kavanaugh A. Curr Opin Rheumatol. 2012;24(3):327–34. Acknowledgements This study was funded by Genentech, Inc. Disclosure of Interest J. Kremer Shareholder of: Corrona, LLC, Consultant for: Abbvie, Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Genentech, GlaxoSmithKline, Pfizer, Regeneron and Sanofi, W. Rigby Consultant for: Roche/Genentech, N. Singer Grant/research support from: Merck/EMD Serono (in kind lab resources) and unrestricted educational grants from several companies to MetroHealth for 2016 Cleveland Society of Rheumatology, C. Birchwood Employee of: Genentech, Inc., D. Gill Employee of: Genentech, Inc., W. Reiss Employee of: Genentech, Inc., J. Best Employee of: Genentech, Inc., J. Pei Employee of: Genentech, Inc., M. Michalska Employee of: Genentech, Inc.

FRI0496 Comparing tofacitinib safety profile in patients with psoriatic arthritis in clinical studies with real-world data

Background Tofacitinib is an oral Janus kinase inhibitor under investigation for the treatment of psoriatic arthritis (PsA). Two Phase 3 studies have been completed (NCT01877668; NCT01882439) and a long-term extension (LTE) study is ongoing (database not locked; NCT01976364). Objectives To compare incidence rates (IR) for adverse events (AEs) of special interest in a tofacitinib cohort from the Phase 3 PsA trials with real-world experience in a comparison cohort from the US Truven MarketScan database. Methods The tofacitinib cohort included adult patients (pts) from 2 Phase 3 studies with ≥6 months PsA diagnosis who met ClASsification of Psoriatic ARthritis (CASPAR) criteria, had active plaque psoriasis, and active arthritis (≥3 swollen and ≥3 tender/painful joints) and who were treated with tofacitinib. Pts were grouped by those who received tofacitinib 5 (N=238) or 10 mg (N=236) twice daily (BID) in the 2 Phase 3 studies, and all pts who received ≥1 dose of tofacitinib in the 2 Phase 3 studies or the LTE (tofacitinib all doses, N=783). The comparison cohort (N=5799) comprised pts with moderate to severe PsA, defined by ≥1 inpatient or ≥2 outpatient 696.0 diagnosis codes on 2 unique calendar days (≥1 by a rheumatologist) between Oct 2010 and Sep 2015, initiating therapy with a systemic agent for PsA. Key Phase 3 study exclusion criteria were applied to the comparison cohort. IRs for serious infection events (SIEs), herpes zoster (HZ), malignancies (excluding non-melanoma skin cancer [NMSC]), NMSC and major adverse cardiovascular events (MACE) were compared. Results Mean age, gender and diabetes history were generally similar between the tofacitinib and comparison cohorts (48.7–49.5 years, 42.4–49.2% male, 12.2–15.7% with diabetes history). Overall more pts treated with tofacitinib had prior experience with corticosteroids (15.7–28.2%), conventional synthetic disease-modifying antirheumatic drugs (100%) and tumour necrosis factor inhibitors (48.1–55.9%) vs the comparison cohort (11.9%, 46.6% and 36.6%, respectively). IRs for SIEs were lower for the tofacitinib vs the comparison cohort (Table 1). The tofacitinib cohort had a higher rate of HZ vs the comparison cohort (Table 1). IRs for malignancies and MACE were similar between cohorts (Table 1). Conclusions IRs of AEs of special interest reported in tofacitinib PsA Phase 3 studies were generally comparable to those in a general PsA population comprising pts receiving a range of biologic agents, except HZ, which was higher for pts treated with tofacitinb but similar to the incidence observed with tofacitinib treatment in other indications. Acknowledgements This study was sponsored by Pfizer Inc. Editorial support was provided by A Pedder of CMC and was funded by Pfizer Inc. Disclosure of Interest J. Curtis Grant/research support from: Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer Inc, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer Inc, H. Yun Grant/research support from: Pfizer Inc, O. FitzGerald Grant/research support from: AbbVie, Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer Inc, Speakers bureau: Celgene, Janssen, Novartis, K. Winthrop Grant/research support from: Bristol-Myers Squibb, Pfizer Inc, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Galapagos, Pfizer Inc, UCB, V. Azevedo Grant/research support from: Bristol-Myers Squibb, GSK, Pfizer Inc, UCB, Consultant for: AbbVie, Bristol-Myers Squibb, Janssen, Merck Serono, Novartis, Pfizer Inc, G. Burmester Grant/research support from: UCB, Consultant for: AbbVie, Bristol-Myers Squibb, Eli Lilly, Hexal, Janssen, MSD, Medimmune, Novartis, Pfizer Inc, Sanofi, Roche, Speakers bureau: AbbVie, Bristol-Myers Squibb, Hexal, MSD, Novartis, Pfizer Inc, Roche, W. F. Rigby Grant/research support from: Amgen, Pfizer Inc, Roche, Consultant for: Bristol-Myers Squibb, Eli Lilly, Pfizer Inc, Roche, K. Kanik Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, R. Rojo Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Menon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, P. Biswas Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, T. Hendrikx Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, N. Palmetto Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

AB0436 Comparison of tofacitinib efficacy in patients with moderate vs severe rheumatoid arthritis: pooled analysis of phase 3 studies

Background Tofacitinib is an oral JAK inhibitor for the treatment of RA. Objectives To evaluate tofacitinib 5 and 10 mg twice daily (BID) efficacy in patients (pts) with moderate vs severe RA. Methods Tofacitinib 5 and 10 mg BID efficacy data were obtained from 6 randomised double-blind Phase 3 studies of 6–24 months duration. Tofacitinib was administered as monotherapy (NCT00814307 ORAL Solo; NCT01039688 ORAL Start) or with csDMARDs, mainly MTX (NCT00960440 ORAL Step; NCT00847613 ORAL Scan; NCT00856544 ORAL Sync; NCT00853385 ORAL Standard). Pts receiving MTX monotherapy (ORAL Start), or placebo (±csDMARDs) were combined as a single “placebo” group. Baseline (BL) disease severity was classified as moderate or severe using Disease Activity Score in 28 joints with erythrocyte sedimentation rate (DAS28: moderate 3.2 to ≤5.1; severe >5.1) and Clinical Disease Activity Index (CDAI: moderate 10 to ≤22; severe >22). Month 3 (M3) efficacy outcomes included: pts (%) achieving low disease activity (LDA; DAS28 ≤3.2, CDAI ≤10), remission (DAS28 <2.6, CDAI ≤2.8), HAQ-DI <0.5 (normal physical functioning), HAQ-DI improvement >0.22 and mean change from BL (Δ) in DAS28, CDAI and HAQ-DI. This post hoc analysis had no multiplicity adjustments. Results Overall, more pts had severe BL disease by DAS28 (91.0%) and CDAI (89.5%). The table shows BL disease characteristics and M3 efficacy outcomes for pts classified by BL DAS28 disease severity; CDAI classification demonstrated similar trends. BL characteristics were balanced between treatment groups in each disease severity category. M3 efficacy was significantly greater with tofacitinib 5 and 10 mg BID vs placebo, regardless of BL disease severity. As expected, larger proportions of tofacitinib-treated pts with moderate vs severe BL RA achieved LDA by either DAS28 (32.3–36.7% vs 13.8–19.1%) or CDAI (49.2–55.0% vs 26.0–31.7%). Similarly, a higher proportion of pts achieved remission in the moderate vs severe BL groups by DAS28 (20.0–22.8% vs 6.2–9.0%) or CDAI (11.5–12.1% vs 5.1–6.7%). A greater proportion of pts achieved HAQ-DI <0.5 with moderate vs severe RA classified by BL DAS28 (45.0–60.6% vs 24.5–30.0%) or BL CDAI (40.8–52.4% vs 24.7–30.4%). Greater improvements from BL in disease activity and HAQ-DI were seen for pts with severe vs moderate RA classified by BL DAS28 (Table), and by BL CDAI (Tofacitinib 5/10 mg BID ΔCDAI: -21.1/-23.0 vs -8.1/-9.4; ΔHAQ DI: -0.5/-0.6 vs -0.3/-0.4). Conclusions Tofacitinib 5 and 10 mg BID demonstrated efficacy in treating pts with moderate and severe RA with >7 years mean disease duration. By M3, pts with severe vs moderate BL disease activity had greater improvements in disease activity and physical functioning; higher proportions of pts with moderate vs severe BL disease activity achieved remission, LDA or normal physical functioning. Interpretation of this post hoc analysis may be limited by the smaller sample size of the moderate disease group and the combining of mono- and combination-therapy results. Acknowledgements This study was sponsored by Pfizer Inc. Editorial support was provided by A Pedder of CMC and funded by Pfizer Inc. Disclosure of Interest S. Schwartzman Consultant for: Pfizer Inc, P. Sunkureddi Grant/research support from: Pfizer Inc, Consultant for: Pfizer Inc, Speakers bureau: Pfizer Inc, L. Takiya Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, M. Snyder Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, H. Fan Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, T. Lukic Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Roberts Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, W. F. Rigby Grant/research support from: Amgen, Pfizer Inc, Roche, Consultant for: Bristol-Myers Squibb, Eli Lilly, Pfizer Inc, Roche