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ObjectivesTo define the instruments for the Assessment of SpondyloArthritis international Society–Outcomes Measures in Rheumatology (ASAS-OMERACT) core domain set for axial spondyloarthritis (axSpA).MethodsAn international working group representing key stakeholders selected the core outcome instruments following a predefined process: (1) identifying candidate instruments using a systematic literature review; (2) reducing the list of candidate instruments by the working group, (3) assessing the instruments’ psychometric properties following OMERACT filter 2.2, (4) selection of the core instruments by the working group and (5) voting and endorsement by ASAS.ResultsThe updated core set for axSpA includes seven instruments for the domains that are mandatory for all trials: Ankylosing Spondylitis Disease Activity Score and Numerical Rate Scale (NRS) patient global assessment of disease activity, NRS total back pain, average NRS of duration and severity of morning stiffness, NRS fatigue, Bath Ankylosing Spondylitis Function Index and ASAS Health Index. There are 9 additional instruments considered mandatory for disease-modifying antirheumatic drugs (DMARDs) trials: MRI activity Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joints and SPARCC spine, uveitis, inflammatory bowel disease and psoriasis assessed as recommended by ASAS, 44 swollen joint count, Maastricht Ankylosing Spondylitis Enthesitis Score, dactylitis count and modified Stoke Ankylosing Spondylitis Spinal Score. The imaging outcomes are considered mandatory to be included in at least one trial for a drug tested for properties of DMARD. Furthermore, 11 additional instruments were also endorsed by ASAS, which can be used in axSpA trials on top of the core instruments.ConclusionsThe selection of the instruments for the ASAS-OMERACT core domain set completes the update of the core outcome set for axSpA, which should be used in all trials.

ObjectivesTofacitinib is a Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ulcerative colitis, and has been investigated in psoriasis (PsO). Routine pharmacovigilance of an ongoing, open-label, blinded-endpoint, tofacitinib RA trial (Study A3921133; NCT02092467) in patients aged ≥50 years and with ≥1 cardiovascular risk factor identified a higher frequency of pulmonary embolism (PE) and all-cause mortality for patients receiving tofacitinib 10 mg twice daily versus those receiving tumour necrosis factor inhibitors and resulted in identification of a safety signal for tofacitinib. Here, we report the incidence of deep vein thrombosis (DVT), PE, venous thromboembolism (VTE; DVT or PE) and arterial thromboembolism (ATE) from the tofacitinib RA (excluding Study A3921133), PsA and PsO development programmes and observational studies. Data from an ad hoc safety analysis of Study A3921133 are reported separately within.MethodsThis post-hoc analysis used data from separate tofacitinib RA, PsO and PsA programmes. Incidence rates (IRs; patients with events per 100 patient-years’ exposure) were calculated for DVT, PE, VTE and ATE, including for populations stratified by defined baseline cardiovascular or VTE risk factors. Observational data from the US Corrona registries (including cardiovascular risk factor stratification), IBM MarketScan research database and the US FDA Adverse Event Reporting System (FAERS) database were analysed.Results12 410 tofacitinib-treated patients from the development programmes (RA: n=7964; PsO: n=3663; PsA: n=783) were included. IRs (95% CI) of thromboembolic events among the all tofacitinib cohorts’ average tofacitinib 5 mg and 10 mg twice daily treated patients for RA, respectively, were: DVT (0.17 (0.09–0.27) and 0.15 (0.09–0.22)); PE (0.12 (0.06–0.22) and 0.13 (0.08–0.21)); ATE (0.32 (0.22–0.46) and 0.38 (0.28–0.49)). Among PsO patients, IRs were: DVT (0.06 (0.00–0.36) and 0.06 (0.02–0.15)); PE (0.13 (0.02–0.47) and 0.09 (0.04–0.19)); ATE (0.52 (0.22–1.02) and 0.22 (0.13–0.35)). Among PsA patients, IRs were: DVT (0.00 (0.00–0.28) and 0.13 (0.00–0.70)); PE (0.08 (0.00–0.43) and 0.00 (0.00–0.46)); ATE (0.31 (0.08–0.79) and 0.38 (0.08–1.11)). IRs were similar between tofacitinib doses and generally higher in patients with baseline cardiovascular or VTE risk factors. IRs from the overall Corrona populations and in Corrona RA patients (including tofacitinib-naïve/biologic disease-modifying antirheumatic drug-treated and tofacitinib-treated) with baseline cardiovascular risk factors were similar to IRs observed among the corresponding patients in the tofacitinib development programme. No signals of disproportionate reporting of DVT, PE or ATE with tofacitinib were identified in the FAERS database.ConclusionsDVT, PE and ATE IRs in the tofacitinib RA, PsO and PsA programmes were similar across tofacitinib doses, and generally consistent with observational data and published IRs of other treatments. As expected, IRs of thromboembolic events were elevated in patients with versus without baseline cardiovascular or VTE risk factors, and were broadly consistent with those observed in the Study A3921133 ad hoc safety analysis data, although the IR (95% CI) for PE was greater in patients treated with tofacitinib 10 mg twice daily in Study A3921133 (0.54 (0.32–0.87)), versus patients with baseline cardiovascular risk factors treated with tofacitinib 10 mg twice daily in the RA programme (0.24 (0.13–0.41)).

ObjectiveTo assess the efficacy/safety of tofacitinib in adult patients with active ankylosing spondylitis (AS).MethodsThis phase III, randomised, double-blind, placebo-controlled study enrolled patients aged ≥18 years diagnosed with active AS, meeting the modified New York criteria, with centrally read radiographs, and an inadequate response or intolerance to ≥2 non-steroidal anti-inflammatory drugs. Patients were randomised 1:1 to receive tofacitinib 5 mg two times per day or placebo for 16 weeks. After week 16, all patients received open-label tofacitinib until week 48. The primary and key secondary endpoints were Assessment of SpondyloArthritis international Society ≥20% improvement (ASAS20) and ≥40% improvement (ASAS40) responses, respectively, at week 16. Safety was assessed throughout.Results269 patients were randomised and treated: tofacitinib, n=133; placebo, n=136. At week 16, the ASAS20 response rate was significantly (pConclusionsIn adults with active AS, tofacitinib demonstrated significantly greater efficacy versus placebo. No new potential safety risks were identified.Trial registration numberNCT03502616

We read with interest the recently published European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis (PsA) with pharmacological therapies1 and the associated systematic literature research (SLR)2; we welcome the clarity that they offer for patient care. We would like to bring three points to your readers’ attention to correct and clarify the narrative supporting Recommendation 7 (Janus kinase (JAK) inhibitors). Recommendation 7 states: “ … Our SLR indicated tofacitinib may have similar efficacy as the TNFi adalimumab for joint involvement, but numerically lower efficacy in skin psoriasis.1,15,72 … Safety signals exist for some infections, especially herpes zoster, as well as a recent signal for deep vein thrombosis especially with a high dose of tofacitinib which is not approved for PsA, but also the usual 5 mg twice daily dose particularly in those with cardiovascular risk factors and older patients.15,72,73” Regarding the statement: “ … as well as a recent signal for deep vein thrombosis especially with a high dose of tofacitinib which is not approved for PsA …”: We would like to respectfully correct this statement, as this signal was seen for pulmonary embolism (PE) rather than deep vein thrombosis (DVT); this was observed in the 10 mg twice daily dose of tofacitinib, …

Background:Treatment effect on pain is a priority for patients (pts) with psoriatic arthritis (PsA) and physicians. As pain is multidimensional, there is growing interest to understand the mechanisms of pain relief during treatment. Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. Previous analyses showed that the effect of tofacitinib on pain in pts with PsA was partially mediated through improvement of inflammation as assessed by C-reactive protein (CRP) and Swollen Joint Count (SJC). Additional potential inflammation-associated mediators that might contribute to tofacitinib’s effect on pain include enthesitis and skin disease.Objectives:To describe the interrelationship between pain, tofacitinib treatment and potential inflammatory-associated outcomes, using mediation modelling.Methods:Data from two Phase 3 studies (OPAL Broaden [NCT01877668]; OPAL Beyond [NCT01882439]) of pts with active PsA treated with tofacitinib 5 mg twice daily (BID) or placebo were used; pts were tumour necrosis factor inhibitor (TNFi)-naïve or had previous inadequate response to ≥1 TNFi. All pts were treated continuously with a single conventional synthetic DMARD. Analyses were completed using pooled and individual study data at Months 1 and 3 (using mean scores across visits). Mediation modelling seeks to explain mechanisms underlying observed relationships between independent and dependent variables via other variables (mediators). This initial model included: treatment as the independent (explanatory) binary variable (tofacitinib 5 mg BID vs placebo); pain, measured by Patient’s Assessment of Arthritis Pain (VAS, 0–100 mm), as the dependent (outcome) variable; mediators were: pt-reported Itch Severity Index (ISI); CRP; SJC; Psoriasis Area and Severity Index (PASI); and enthesitis, measured by Leeds Enthesitis Index (LEI) or Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC). The final model was revised based on results of the initial model.Results:The initial model (N=329; pooled data) showed that tofacitinib treatment affects pain mainly indirectly via ISI, CRP, SJC, PASI and enthesitis (LEI), with 16.0% (p=0.53) attributable to the direct effect. The indirect effect via SJC (Conclusion:The majority of tofacitinib treatment effect on pain in pts with PsA is collectively mediated by itch, enthesitis and CRP, with itch being the main mediator of treatment effect (~37%), using mediation modelling analyses.Acknowledgments:Study sponsored by Pfizer Inc. Medical writing support was provided by Eric Comeau of CMC Connect and funded by Pfizer Inc.Disclosure of Interests:Peter C. Taylor Grant/research support from: Celgene, Eli Lilly and Company, Galapagos, and Gilead, Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Roche, and UCB, Kurt de Vlam Grant/research support from: Celgene, Eli Lilly, Pfizer Inc, Consultant of: AbbVie, Eli Lilly, Galapagos, Johnson & Johnson, Novartis, Pfizer Inc, UCB, Andrew G Bushmakin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lara Fallon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph F. Merola Consultant of: Merck, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB Pharma, Celgene, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres and LEO Pharma, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ming-Ann Hsu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau

Background:Current treatments for PsA have proven effective in reducing patient (pt)-reported pain;1,2however, residual pain often remains. Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA.Objectives:This descriptive analysis evaluated the effect of tofacitinib, adalimumab and placebo on residual pain in pts with PsA whose inflammation was attenuated after 3 months of therapy.Methods:Data were included from OPAL Broaden (NCT01877668), a randomised, double-blind, placebo-controlled Phase 3 trial of 12 months’ duration in pts with PsA.3Pts were randomised to receive tofacitinib 5 mg twice daily (BID), tofacitinib 10 mg BID, adalimumab 40 mg subcutaneous injection once every 2 weeks or placebo. This analysis assessed pts with ‘residual pain’ at Month (M)3. Residual pain was considered as pain in pts with complete attenuation of inflammation at M3, defined by a swollen joint count (SJC) of 0 and CRP levels Results:Demographics and baseline disease characteristics have previously been reported in the primary study, and were generally similar between treatment groups.3At M3, 100/422 (23.7%) pts with PsA had achieved SJC of 0 and CRP Conclusion:Changes from baseline in pain and absolute pain at M3 suggest that in pts with PsA whose inflammation has been completely attenuated, tofacitinib might have an effect on residual pain not obviously attributable to inflammation. However, the sample population was small, and there were large standard deviations. To confirm these results and to understand the mechanisms by which tofacitinib may improve residual pain, a meta-analysis will be performed using individual participant data from pts with rheumatic disease who have participated in tofacitinib randomised controlled trials.References:[1]Gladman et al. Ann Rheum Dis 2007;66:163-68.[2]Gladman et al. Arthritis Care Res 2014;66:1085-92.[3]Mease et al. NEJM 2017;377:1537-50.Acknowledgments:Study sponsored by Pfizer Inc. Medical writing support was provided by Mark Bennett of CMC Connect and funded by Pfizer Inc.Disclosure of Interests:Maxime Dougados Grant/research support from: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Speakers bureau: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV, Clifton Bingham Grant/research support from: Bristol-Myers Squibb, Consultant of: Bristol-Myers Squibb, Peter C. Taylor Grant/research support from: Celgene, Eli Lilly and Company, Galapagos, and Gilead, Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Roche, and UCB, Lara Fallon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, John Woolcott Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Yves Brault Shareholder of: Pfizer France, Employee of: Pfizer France, Lisy Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Meriem Kessouri Shareholder of: Pfizer France, Employee of: Pfizer France

Background:Ankylosing spondylitis (AS) can significantly impact quality of life. Tofacitinib is an oral Janus kinase inhibitor under investigation for the treatment of adult patients (pts) with AS. The safety/efficacy (including pt-reported outcomes [PROs]) of tofacitinib in pts with AS was assessed in a Phase 3 trial (NCT03502616).1Objectives:To evaluate the effect of tofacitinib on pt-reported pain, fatigue, overall health and work productivity in pts with active AS enrolled in the Phase 3 trial.Methods:Pts with an inadequate clinical response or intolerance to ≥2 oral NSAIDs were randomised in a double-blind fashion to tofacitinib 5 mg twice daily (BID) or placebo (PBO) for 16 weeks. At Week (W)16, all pts received open-label tofacitinib 5 mg BID up to W48. Least squares (LS) mean changes from baseline (Δ) up to W48 are reported for the following outcomes: pt assessment of nocturnal spinal pain, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Short Form-36 Health Survey version 2 (SF-36v2; W16 and W48 only), and Work Productivity and Activity Impairment Questionnaire (WPAI; W16 and W48 only).Results:At W16, there were greater improvements from baseline in pain (total back pain [previously published1] and nocturnal spinal pain) and fatigue (FACIT-F total score; experience and impact domain scores) with tofacitinib vs PBO (p≤0.05; Table 1); improvements were observed as early as W2. Also, improvements in SF-36v2 physical component summary (PCS) (Table 1), and physical functioning, role-physical, bodily pain, general health and social functioning domains (Figure 1) were greater with tofacitinib vs PBO at W16 (p≤0.05). Similarly, improvements in WPAI scores at W16 were greater with tofacitinib vs PBO (p≤0.05), except for % work time missed (Table 1). Improvements with tofacitinib continued up to W48 (Table 1/Figure 1). Generally, pts receiving PBO who advanced to tofacitinib at W16 reported similar improvements after switching to tofacitinib (Table 1/Figure 1).Table 1.PROs at baseline and Δ at W16 and W48Baseline,mean (SD) [N1]Δ, W16,LS mean (SE)Δ, W48,LS mean (SE)Tofacitinib5 mg BID (N=133)PBO(N=136)Tofacitinib5 mg BIDPBOp valueTofacitinib5 mg BIDPBO→tofacitinib5 mg BIDNocturnalspinal paina6.8 (1.9)6.8 (1.9)-2.67 (0.20)-0.84 (0.20)-3.52 (0.23)-3.01 (0.23)FACIT-Ftotal scorea,b27.2 (10.7)27.4 (9.3)6.54 (0.80)3.12 (0.79)0.00089.54 (0.90)7.35 (0.89)FACIT-F experience domaina8.9 (4.3)8.7 (4.0)2.85 (0.36)1.29 (0.36)0.00074.22 (0.40)3.40 (0.40)FACIT-Fimpactdomaina18.3 (6.9)18.8 (5.9)3.68 (0.49)1.81 (0.49)0.00285.32 (0.54)3.95 (0.54)SF-36v2 PCSb,c33.5 (7.3)33.1 (7.0) [135]6.69 (0.59)3.14 (0.59)8.81 (0.720)7.39 (0.71)SF-36v2 MCSc39.4 (11.1)39.8 (12.7) [135]3.45 (0.91)2.13 (0.92)0.25297.07 (0.93)6.35 (0.92)WPAIc% activity impairment56.5 (23.4)56.0 (21.4)-19.03 (1.97)-5.63 (1.97)-27.37 (2.34)-19.77 (2.31)% work time missed9.9 (22.4) [81]11.5 (24.6) [88]-3.65 (2.66)0.88 (2.62)0.1784-8.10 (2.14)-5.79 (2.05)% impairment while working48.4 (26.3) [79]49.6 (22.2) [85]-19.83 (2.27)-6.94 (2.30)-25.35 (2.77)-23.00 (2.66)% overall work impairment50.8 (27.4) [79]53.5 (23.1) [85]-21.49 (2.51)-7.64 (2.56)-27.63 (3.01)-23.22 (2.90)aMMRMbGlobal type I error-controlled endpointcAnalysis of covariance model for W16 and MMRM for W48MCS, mental component summary; MMRM, Mixed Model for Repeated Measures; N, number of pts in full analysis set; N1, number of pts included in the analysis (if different from N); SD, standard deviation; SE, standard errorConclusion:In pts with active AS, improvements in spinal pain, fatigue, overall health and work productivity were greater with tofacitinib vs PBO at W16; improvements continued up to W48. These PRO findings support the primary efficacy results of this Phase 3 trial,1 and add to the overall understanding of the benefit/risk profile of tofacitinib in patients with AS.References:[1]Deodhar et al. Arthritis Rheumatol 2020; 72 (S10): Abs L11.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by Emma Mitchell, CMC Connect, and funded by Pfizer Inc.Disclosure of Interests:Victoria Navarro-Compán Speakers bureau: AbbVie, Eli Lilly, Janssen, MSD, Novartis, Pfizer Inc, UCB, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer Inc, UCB, Grant/research support from: AbbVie, Novartis, James Cheng-Chung Wei Speakers bureau: Eli Lilly, Janssen, Novartis, Pfizer Inc, Consultant of: Eli Lilly, Novartis, Pfizer Inc, Grant/research support from: AbbVie, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, UCB, Filip van den Bosch Shareholder of: AbbVie, Celgene, Eli Lilly, Galapagos, Gilead, Merck, Novartis, Pfizer Inc, UCB, Marina Magrey: None declared, Lisy Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Dona Fleishaker Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Cunshan Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph Wu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Oluwaseyi Dina Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lara Fallon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Vibeke Strand Consultant of: AbbVie, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Corrona, Eli Lilly, Galapagos, Genentech/Roche, Gilead, GSK, Ichnos, Inmedix, Janssen, Kiniksa, Merck, Myriad Genetics, Novartis, Pfizer Inc, Regeneron, Samsung, Sandoz, Sanofi, Scipher, SetPoint Medical, UCB

Background:Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). It was approved in the United States (US) in December 2017 for use in combination with non-biologic disease-modifying antirheumatic drugs (DMARDs).Objectives:This analysis of real-world data assessed demographic and baseline clinical characteristics, as well as treatment persistence/adherence, in patients (pts) with PsA who had newly initiated tofacitinib treatment.Methods:This retrospective cohort study included pts aged ≥18 years in the Truven MarketScan™ US Commercial and Medicare Supplemental Claims and Encounters database with ≥1 tofacitinib claim (first = index) between 14 December 2017–30 April 2019, and PsA diagnoses (≥1 inpatient or ≥2 outpatient [30–365 days apart]) on or within 12 months pre-index. Pts were continuously enrolled for 12 months pre-index and 6 months post-index, with no pre-index claims for tofacitinib. Pt demographic and clinical characteristics on the day of index, history of advanced therapy treatment (≥1 claim for biologic DMARDs or apremilast within 12 months pre-index) and tofacitinib treatment regimen (monotherapy or combination therapy [≥1 claim for conventional synthetic DMARDs or apremilast on or within 90 days post-index]) were recorded. Outcomes at 6 months post-index included tofacitinib persistence (Results:Of 17 321 pts receiving tofacitinib, 440 pts met the inclusion criteria for the overall cohort, with 315 pts included in the sub-cohort. In the overall cohort, pts were mostly female, with a mean age of 52.3 years and a mean PsA duration of 738 days (data not shown). Most pts were exposed to ≥1 advanced therapy within 12 months pre-index (mean = 1.1; range = 0–4); most commonly secukinumab (Table 1). Overall, 60.7% of pts received monotherapy and 39.3% of pts received tofacitinib combination therapy post-index; most commonly methotrexate (data not shown). At 6 months post-index, persistence was similar in pts receiving tofacitinib monotherapy vs combination therapy; adherence was slightly lower in pts receiving tofacitinib monotherapy vs combination therapy (Figure 1). Results were similar in the sub-cohort (Table 1, Figure 1).Table 1.History of advanced therapy on or within 12 months pre-index in pts with PsAAll pts(N=440)Pts with no RAa(N=315)Pts exposed to advanced therapy, n (%)b Any advanced therapyc336 (76.4)241 (76.5) Secukinumab113 (25.7)91 (28.9) Adalimumab93 (21.1)58 (18.4) Apremilast81 (18.4)59 (18.7) Etanercept70 (15.9)47 (14.9)Unique advanced therapy prescriptions Mean (SD)1.1 (0.8)1.1 (0.8) Median (IQR)1 (1–2)1 (1–2) Range0–40–4Number of unique advanced therapies, n (%) 0104 (23.6)74 (23.5) 1214 (48.6)153 (48.6) 2100 (22.7)73 (23.2) ≥322 (5.0)15 (4.8)aExcludes pts with a diagnosis of RA on or within 12 months pre-index and within 6 months post-index; bPts with ≥1 claim for biologic DMARDs or apremilast within 12 months pre-index; cOther advanced therapies reported in IQR, interquartile range; N, number of pts per cohort; n, number of pts per category; SD, standard deviationFigure 1Conclusion:This analysis of US-based claims data indicated that pts newly initiated tofacitinib treatment an average of 2 years after PsA diagnosis, with the majority (>60%) of pts receiving tofacitinib as monotherapy. High levels of persistence and adherence to tofacitinib were observed 6 months after treatment initiation. Findings were similar when pts with PsA who also had a diagnosis of RA were excluded. Data were limited in that claims data cannot confirm that pts took the medication for which they filed a claim.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by Gemma Turner, CMC Connect, and funded by Pfizer Inc.Disclosure of Interests:Philip J Mease Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech, Janssen, Novartis, Pfizer Inc, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer Inc, Sun, UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer Inc, Sun, UCB, Pamela Young Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, David C Gruben Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lara Fallon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Rebecca Germino Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Arthur Kavanaugh Grant/research support from: Pfizer Inc.

Background:Tofacitinib is an oral JAK inhibitor for the treatment of psoriatic arthritis (PsA).Objectives:To assess tofacitinib 5 mg BID as monotherapy after methotrexate (MTX) withdrawal vs with continued background MTX in patients (pts) with PsA.Methods:OPAL Balance (NCT01976364) was an open-label (OL) long-term extension (LTE) study of tofacitinib in pts with PsA who participated in Phase (P)3 studies (OPAL Broaden,NCT01877668; OPAL Beyond,NCT01882439). Pts who completed ≥24 months’ tofacitinib treatment in the LTE (stable 5 mg BID for ≥3 months) and were receiving oral MTX (7.5–20 mg/week; stable for ≥4 weeks) entered the multicentre, 12-month, double-blind, MTX withdrawal substudy. Pts remained on OL tofacitinib 5 mg BID and were randomised 1:1 to receive placebo (tofacitinib monotherapy, ie, blinded MTX withdrawal) or MTX (tofacitinib + MTX; same stable doses). Primary endpoints were changes from substudy baseline (Δ) in PASDAS and HAQ-DI at Month (M)6. Secondary efficacy endpoints were assessed at all time points. Safety was assessed throughout the substudy.Results:Of 180 pts randomised, 179 were treated (tofacitinib monotherapy n=90; tofacitinib + MTX n=89). Pt characteristics were similar between treatment arms. At M6, least squares mean (LSM) (standard error [SE]) ΔPASDAS was 0.229 (0.079) for tofacitinib monotherapy and 0.138 (0.081) for tofacitinib + MTX, and LSM (SE) ΔHAQ-DI was 0.043 (0.027) and 0.017 (0.028), respectively (Figure 1); no clinically meaningful differences were observed. Efficacy and pt-reported outcomes were generally similar between treatment arms at M6 and M12 (data not shown). Rates of pts achieving minimal disease activity, and maintaining an absence of enthesitis and dactylitis, were sustained to M12 in both treatment arms (Figure 2). Adverse event rates (Table) and laboratory parameters were comparable between treatment arms, but liver enzyme elevations were more common with tofacitinib + MTX.Conclusion:No clinically meaningful differences in efficacy and safety were observed in PsA pts who received OL tofacitinib 5 mg BID as monotherapy after MTX withdrawal vs with continued MTX. Safety was consistent with previous P3 studies. The substudy was an estimation study and not powered for hypothesis testing.Table.Safety outcomes to Month 12Pts with events, n (%) AEs of special interestTofacitinib monotherapy N=90Tofacitinib + MTXN=89AE43 (47.8)41 (46.1)Serious AE4 (4.4)3 (3.4)Discontinuations due to AE3 (3.3)4 (4.5)Death00 Herpes zoster (serious/non-serious)1 (1.1)2 (2.2) Serious infection02 (2.2) Opportunistic infectiona01 (1.1) Malignancy (excl. NMSC)a1 (1.1)1 (1.1) NMSCa00 Major adverse cardiovascular eventa00 Venous thromboembolismc00 Arterial thromboembolismc1 (1.1)0 Gastrointestinal perforationa00 Interstitial lung diseaseb00Laboratory parametersdALT ≥3×ULN05 (5.6) ALT (IU/L), mean (SE)-2.7 (1.6)2.5 (1.3)AST ≥3×ULN03 (3.4) AST (IU/L), mean (SE)-1.5 (1.2)1.7 (0.8)Reviewed by independentaexternal/binternal adjudication committeecPer Standardised MedDRA Query termsdWithout regard to baseline abnormalityALT, alanine aminotransferase; AST, aspartate aminotransferase; ULN, upper limit of normalAcknowledgments:Study sponsored by Pfizer Inc. Medical writing support was provided by Christina Viegelmann of CMC Connect and funded by Pfizer Inc.Disclosure of Interests:Peter Nash Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Laura C Coates: None declared, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau, Alan Kivitz Shareholder of: AbbVie, Amgen, Gilead, GSK, Pfizer Inc, Sanofi, Consultant of: AbbVie, Boehringer Ingelheim,,Flexion, Genzyme, Gilead, Janssen, Novartis, Pfizer Inc, Regeneron, Sanofi, SUN Pharma Advanced Research, UCB, Paid instructor for: Celgene, Genzyme, Horizon, Merck, Novartis, Pfizer, Regeneron, Sanofi, Speakers bureau: AbbVie, Celgene, Flexion, Genzyme, Horizon, Merck, Novartis, Pfizer Inc, Regeneron, Sanofi, Dafna D Gladman Grant/research support from: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – grant/research support, Consultant of: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – consultant, Frank Behrens Grant/research support from: Pfizer, Janssen, Chugai, Celgene, Lilly and Roche, Consultant of: Pfizer, AbbVie, Sanofi, Lilly, Novartis, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche and Chugai, James Cheng-Chung Wei Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Eisai, Janssen, Novartis, Pfizer Inc, Sanofi-Aventis, UCB Pharma, Dona Fleishaker Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph Wu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Cunshan Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ana Belen Romero Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lara Fallon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ming-Ann Hsu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Keith Kanik Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

Background:Long delays in the diagnosis of ankylosing spondylitis (AS) and in receiving advanced therapies signify a critical unmet need. Little is known about delays or treatment patterns in Central Eastern European (CEE) countries.Objectives:To describe patient time to diagnosis of and its treatment patterns in CEE and the US.Methods:Data were collected via a cross-sectional survey of rheumatologists in Czech Republic, Poland, Russia, Ukraine (Sept–Dec 2019) and US (Jun–Aug 2018) via physician-completed patient record forms. In consecutive patients with a physician-reported diagnosis of AS, rheumatologists recorded patient demographics, clinical features, time to first consultation and diagnosis and treatment history. Data were compared for CEE vs US using t-test for independent samples (continuous outcomes) and Fisher’s exact test (categorical outcomes). Low rates of HLA-B27 and sacroiliitis at diagnosis may reflect combining non-radiographic axial spondyloarthritis under the diagnosis of AS in real-world practice.Results:209 physicians (121 CEE; 88 US) provided data for 1363 patients (876 CEE; 487 US). While some demographic differences existed between regions, estimated prevalence of HLA-B27 in patients with AS was the same between US and CEE. Not all patients were stated to have sacroiliitis at diagnosis (Table 1). Time to first consultation and time to diagnosis were longer in CEE, with more patients experiencing a delay due to another condition initially being diagnosed (Table 2). At diagnosis a similar proportion of patients in CEE and US were prescribed NSAIDs, with higher use of csDMARDs in CEE. bDMARDs were more commonly prescribed at diagnosis in the US, with increased usage continuing after diagnosis (Figure 1).Table 1.Patient demographic and clinical characteristicsCEE(n=876)US(n=487)P value*Demographic characteristicsAge, mean (SD)45.4 (12.7)46.4 (14.1)0.21 (TT)Male, n (%)6319 (72.0)344 (70.6)0.62 (FE)BMI, mean (SD)25.9 (4.1)27.4 (4.5)Full time employment, n (%)460 (53.9)342 (70.8)Caucasian, n (%)853 (97.4)393 (80.7)Clinical features at diagnosisHLA-B27 positive, n (%)592 (67.6)329 (67.6)1.00 (FE)Inflammatory back pain, n (%)712 (82.0)369 (76.7)0.02 (FE)Sacroiliitis identified by X-ray, n (%)598 (68.9)272 (56.5)Back pain >3 months, n (%)427 (49.2)225 (46.8)0.46 (FE)Physician perceived severity, n (%)0.02 (FE)- Mild69 (8.7)20 (5.1)- Moderate414 (52.1)233 (59.1)- Severe312 (39.2)141 (35.8)*Statistical test legend: TT=t-test; FE=Fisher’s Exact.Table 2.Patient diagnosis journeyCEE(n=876)US(n=487)P value*Time from first symptoms to first consultationα, mean months (SD)27.7 (53.7)18.5 (57.1)0.02 (TT)Time from first consultationαto diagnosis, mean months (SD)17.8 (48.6)6.0 (13.2)0.02 (TT)Reasons for delayβ, n (%)- Other condition initially diagnosed108 (33.3)9 (11.8)- Waiting for referral to correct HCP69 (21.3)22 (28.9)0.17 (FE)- Needed test conducting to confirm diagnosis100 (30.9)21 (27.6)0.68 (FE)*Statistical test legend: TT=t-test; FE=Fisher’s exact;αFirst consultation with any healthcare professional about AS symptoms;βDelay defined as >3 months from first consultation to diagnosis.Conclusion:Time to diagnosis was three times longer in CEE vs the US. Despite similar prescription of NSAIDs at diagnosis in US and CEE, a greater proportion of patients currently received NSAIDs and csDMARDs in CEE, while bDMARD use in the US was greater. This suggests different treatment approaches and differences in medication access across the regions.Disclosure of Interests:Tatiana Korotaeva Grant/research support from: Pfizer, Consultant of: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Speakers bureau: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Oluwaseyi Dina Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Elizabeth Holdsworth Employee of: Adelphi Real World, Lara Fallon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Gary Milligan Employee of: Adelphi Real World, Sophie Meakin Employee of: Adelphi Real World, Lisy Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Radu Serban VASILESCU Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB

Background:With multiple disease domains affected in PsA, clinical and patient-reported outcome (PRO) measures are important to assess disease improvement following treatment. Rapid, meaningful improvements in disease activity are a priority for physicians and patients (pts). Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. Higher proportions of pts achieved responses in PROs and clinical measures when treated with tofacitinib for 3 months vs placebo (PBO).1-5Proportions of responders were also similar between tofacitinib and adalimumab (ADA) after 3, 6 and 12 months.2,3,5Objectives:To determine the time to initial response using responder definitions for selected PROs and clinical endpoints in pts with active PsA treated with tofacitinib, ADA or PBO switching to tofacitinib.Methods:In this post hoc analysis, data were collected from two Phase 3 studies (OPAL Broaden [12 months;NCT01877668]; OPAL Beyond [6 months;NCT01882439]).3,4Pts receiving tofacitinib 5 or 10 mg twice daily (BID), subcutaneous ADA 40 mg once every two weeks (Q2W; OPAL Broaden only), or PBO switching to tofacitinib 5 or 10 mg BID at Month (M)3, were included. Responder definitions included: HAQ-DI ≥0.35-point improvement from baseline (BL), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) total score ≥4-point improvement from BL, minimal disease activity (MDA) yes/no composite response (meeting at least 5 of 7 criteria) and PsA Disease Activity Score (PASDAS) post-BL score of ≤3.2 and >1.6-point improvement from BL. First post-BL data were collected at Week 2 (eg for HAQ-DI) or M1. Time-to-event analyses were performed using the Kaplan-Meier (KM) method, with pts censored at the last observed visit. Log-rank tests compared time to initial response across treatment groups.Results:KM analyses show days to initial response (Figure 1, Figure 2). Time to initial HAQ-DI response was significantly different between treatment groups in OPAL Broaden (pConclusion:Times to initial response in functional ability and disease activity were similar in pts treated with either tofacitinib or ADA. Time to initial response prior to first post-BL observation (Week 2 or M1) was not estimable in this analysis. These results may help physicians better understand the time frame for a meaningful response in pts receiving tofacitinib.References:[1]Strand et al. RMD Open 2019;5:e000808.[2]Strand et al. RMD Open 2019;5:e000806.[3]Mease et al. NEJM 2017;377:1537-50.[4]Gladman et al. NEJM 2017;377:1525-36.[5]Helliwell et al. Arthritis Res Ther 2018;20:242.Acknowledgments:Study sponsored by Pfizer Inc. Medical writing support was provided by Eric Comeau of CMC Connect and funded by Pfizer Inc.Disclosure of Interests:Dafna D Gladman Grant/research support from: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – grant/research support, Consultant of: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – consultant, Laura C Coates: None declared, Joseph Wu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lara Fallon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ming-Ann Hsu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Andrew G Bushmakin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Elizabeth Bacci Employee of: Evidera, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Philip Helliwell: None declared

Background Tofacitinib is an oral JAK inhibitor for treatment of rheumatoid arthritis (RA). Open-label, long-term extension (LTE) studies have enrolled tofacitinib-treated patients (pts) to evaluate safety and efficacy over time. Time on treatment is considered a composite measure of efficacy and safety; discontinuation (D/C) is often due to lack of efficacy (LOE) and/or adverse events (AEs) for disease-modifying antirheumatic drugs (DMARDs). 1 Objectives To estimate drug survival of tofacitinib up to 84 months (mo) in LTE studies and describe reasons for D/C. Methods Data were pooled from two LTE studies (NCT00413699 [up to April 2014; study ongoing, database unlocked] and NCT00661661 [completed]). Of 6553 pts from Phase (P) 1, 2 and 3 studies, 4858 pts (74.1%) received treatment in LTE studies. Tofacitinib 5 or 10 mg BID were initiated as monotherapy or with background DMARDs; pooled data and data for each dose ± background DMARDs were analysed. Pts were assigned tofacitinib 5 or 10 mg BID based on average daily dose in LTE. Kaplan-Meier (K-M) analyses estimated drug survival in tofacitinib-treated pts who withdrew for any reason, due to LOE or due to AE in the LTE, including pts who had previously responded to and tolerated treatment in P1P2P3 studies. Ongoing pts were censored as of April 2014, while pts completing the trial(s) were censored at their completion date. Safety data were included over 84 mo and efficacy data up to 72 mo due to limited pt numbers after 72 mo for efficacy. Retention data were divided into dose and mono vs combination therapy. Results 4858 pts were treated for a mean (maximum) duration of 2.5 (6.9) years (yrs) (results previously reported). 2 Overall, median survival for all tofacitinib treated pts was 5.2 yrs [95% CI 5.0, 5.6] (Figure 1). Median survival for pts receiving tofacitinib with background DMARDs or as monotherapy was 5.3 [4.9, 5.7] and 5.4 [4.8, not evaluable] yrs, respectively. K-M estimates appear similar between 5 and 10 mg BID, median survival was 5.4 [4.9, 5.9] and 5.0 [4.7, 5.5] yrs, respectively (Figure 1). The D/C rate due to LOE was considerably lower than due to AEs (AEs: 17.8%, 22.9%, 15.6%; LOE: 2.7%, 3.3%, 2.5% for all tofacitinib, 5 or 10 mg BID, respectively). The most commonly reported reasons for D/C due to AEs by class were infections/infestations (7.2%, 7.8%, 7.0%), investigations (3.1%, 4.6%, 2.5%) and neoplasms (benign, malignant, unspecified) (2.7%, 3.9%, 2.1%) for all tofacitinib, 5 or 10 mg BID, respectively. Conclusions Drug survival in LTE studies provides early information on the long-term safety, efficacy and tolerability of a therapy. In this analysis, median survival of tofacitinib was approximately 5 yrs, with D/C more commonly associated with AEs than LOE. Similar survival medians were observed for the 5 and 10 mg BID dose groups and monotherapy vs background DMARD therapy. These data support the use of tofacitinib for long-term management of RA. References Neovius M et al. Ann Rheum Dis 2015; 74: 354–360. Wollenhaupt J et al. Arthritis Rheumatol 2014; 66: S375. Acknowledgement This study was sponsored by Pfizer Inc. Editorial support was provided by CMC (funded by Pfizer Inc). Disclosure of Interest J. Pope Grant/research support from: Pfizer, Consultant for: Pfizer, E. Keystone Grant/research support from: Pfizer, Consultant for: Pfizer, Speakers bureau: Pfizer, S. Jamal Grant/research support from: Pfizer, Consultant for: Pfizer, L. Wang Shareholder of: Pfizer, Employee of: Pfizer, L. Fallon Shareholder of: Pfizer, Employee of: Pfizer, J. Woolcott Shareholder of: Pfizer, Employee of: Pfizer, I. Lazariciu Consultant for: Pfizer, Employee of: Quintiles Inc, B. Haraoui Grant/research support from: Pfizer, Consultant for: Pfizer

Background Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). Treatment guidelines recommend targeting remission or low disease activity (LDA), herein defined as Disease Activity Scores ≤3.2 based on 28 joint counts (DAS28≤3.2) and adjusting therapy after 3–6 months1 (Mos). Predicting the likelihood of clinical response may help inform early treatment decisions. Objectives To understand the relationship between timing and magnitude of early changes in DAS28, erythrocyte sedimentation rate (DAS28-4[ESR]) and the likelihood of achieving LDA at Mo 6 in RA patients (pts) naive to methotrexate (MTX). Methods In a Phase 3 study (ORAL Start; NCT01039688), MTX-naive RA pts were randomised 2:2:1 to the following monotherapies: tofacitinib 5 mg twice daily (BID), tofacitinib 10 mg BID or MTX. Conditional probability of pts achieving LDA at Mo 6 were calculated, given failure to achieve DAS28-4(ESR) improvement from baseline (range ≥0.3 to 1.8) at Mo 1 or 3. One-year data with non-responder imputation for missing values was used. Results 948 pts received treatment; tofacitinib 5 mg BID (n=370), tofacitinib 10 mg BID (n=394) or MTX (n=184); results previously reported.2 In this post-hoc analysis, of those patients who failed to achieve DAS28-4(ESR) improvement from baseline ≥1.2 at Mo 3, 6.8% for tofacitinib 5 mg BID, 11.3% for tofacitinib 10 mg BID and 6.2% for MTX achieved LDA at Mo 6 (Table). A minority of pts (74/353 [20.9%]) receiving tofacitinib 5 mg BID failed to achieve DAS28-4(ESR) improvement ≥1.2 from baseline at Mo 3, while a greater proportion failed for MTX (65/171 [38.0%]). Failure to achieve DAS28-4(ESR) improvement from baseline at Mo 3 (range ≥0.30–1.8) for tofacitinib 5 mg BID and MTX was associated with a low probability (≤10%) of achieving LDA at Mo 6. For tofacitinib 5 mg BID, failure to achieve lower thresholds of DAS28-4(ESR) improvement (range ≥0.3 to 0.9) at Mo 1 was associated with lower probability of LDA at Mo 6 than higher DAS28-4(ESR) thresholds (≥1.2–1.8) (Table). Conclusions Failure to achieve DAS28-4(ESR) improvement ≥1.2 from baseline at Mo 3 was associated with a low probability of achieving LDA at Mo 6 (≤6.8%) for tofacitinib 5 mg BID and MTX. For the minority of MTX-naive RA pts treated with tofacitinib 5 mg BID or MTX who failed to achieve a minimal clinical response (DAS28-4[ESR] improvement ≥1.2) by Mo 3, another treatment option can be considered at Mo 3, as there is a low probability of reaching LDA at Mo 6. References Smolen J et al. Ann Rheum Dis 2016;75(1):3–15. Lee EB et al. N Engl J Med 2014;370:2377–2386. Acknowledgement This study was sponsored by Pfizer Inc. Editorial support was provided by Rebecca Bright, PhD, of Complete Medical Communications, and funded by Pfizer Inc. Disclosure of Interest E. Keystone Grant/research support from: Pfizer Inc, Consultant for: Pfizer Inc, Speakers bureau: Pfizer Inc, R. F. van Vollenhoven Grant/research support from: Pfizer Inc, Consultant for: Pfizer Inc, B. Wilkinson Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Fallon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L.-J. Hwang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, D. Chapman Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, R. DeMasi Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, E. B. Lee Consultant for: Pfizer Inc