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Early and sustained efficacy with apremilast monotherapy in biological-naïve patients with psoriatic arthritis: a phase IIIB, randomised controlled trial (ACTIVE)
  1. Peter Nash1,
  2. Kamal Ohson2,
  3. Jessica Walsh3,
  4. Nikolay Delev4,
  5. Dianne Nguyen4,
  6. Lichen Teng4,
  7. Juan J Gómez-Reino5,
  8. Jacob A Aelion6
  9. on behalf of the ACTIVE investigators
    1. 1 Department of Medicine, University of Queensland, Brisbane, Queensland, Australia
    2. 2 Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada
    3. 3 Department of Internal Medicine, Division of Rheumatology, University of Utah School of Medicine, Salt Lake City, Utah, USA
    4. 4 Celgene Corporation, Summit, New Jersey, USA
    5. 5 Hospital Clínico Universitario, Santiago, Spain
    6. 6 West Tennessee Research Institute, Jackson, Tennessee, USA
    1. Correspondence to Professor Peter Nash, Department of Medicine, University of Queensland, Brisbane, QLD 4072, Australia; drpnash{at}tpg.com.au

    Abstract

    Objective Evaluate apremilast efficacy across various psoriatic arthritis (PsA) manifestations beginning at week 2 in biological-naïve patients with PsA.

    Methods Patients were randomised (1:1) to apremilast 30 mg twice daily or placebo. At week 16, patients whose swollen and tender joint counts had not improved by ≥10% were eligible for early escape. At week 24, all patients received apremilast through week 52.

    Results Among 219 randomised patients (apremilast: n=110; placebo: n=109), a significantly greater American College of Rheumatology 20 response at week 16 (primary outcome) was observed with apremilast versus placebo (38.2% (42/110) vs 20.2% (22/109); P=0.004); response rates at week 2 (first assessment) were 16.4% (18/110) versus 6.4% (7/109) (P=0.025). Improvements in other efficacy outcomes, including 28-joint count Disease Activity Score (DAS-28) using C reactive protein (CRP), swollen joint count, Health Assessment Questionnaire-Disability Index (HAQ-DI), enthesitis and morning stiffness severity, were observed with apremilast at week 2. At week 16, apremilast significantly reduced PsA disease activity versus placebo, with changes in DAS-28 (CRP) (P<0.0001), HAQ-DI (P=0.023) and Gladman Enthesitis Index (P=0.001). Improvements were maintained with continued treatment through week 52. Over 52 weeks, apremilast’s safety profile was consistent with prior phase 3 studies in psoriasis and PsA. During weeks 0–24, the incidence of protocol-defined diarrhoea was 11.0% (apremilast) and 8.3% (placebo); serious adverse event rates were 2.8% (apremilast) and 4.6% (placebo).

    Conclusions In biological-naïve patients with PsA, onset of effect with apremilast was observed at week 2 and continued through week 52. The safety profile was consistent with previous reports.

    Trial registration number NCT01925768; Results.

    • spondyloarthritis
    • Das28
    • disease activity
    • treatment
    • psoriatic arthritis

    This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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    Footnotes

    • Handling editor Tore K Kvien

    • Contributors All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. PN had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study conception and design: PN and ND. Acquisition of data: ND and DN. Analysis and interpretation of data: all authors. Statistical expertise: LT.

    • Funding This study was sponsored by Celgene Corporation.

    • Competing interests PN has received grant/research support and honoraria from Celgene Corporation. KO has received grant/research support from Celgene Corporation. JW has received non-financial support from Amgen Inc, Pfizer and UCB and has received personal fees from Celgene Corporation and Novartis. ND, DN and LT are employees of Celgene Corporation. JJG-R has received grant/research support from Roche and Schering-Plough and has served as a consultant to Bristol-Myers Squibb, Pfizer, Roche, Schering-Plough and UCB. JAA has received grant/research support from AbbVie Inc, Ardea Biosciences, Inc, AstraZeneca, Bristol-Myers Squibb, Celgene Corporation, Centocor, Galápagos, Genentech Inc, GlaxoSmithKline, Human Genome Sciences, Janssen, Eli Lilly and Company, Merck & Co, Mesoblast, Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer, Roche, Sanofi-Aventis, Takeda Pharmaceuticals, UCB and Vertex Pharmaceuticals.

    • Patient consent Obtained.

    • Ethics approval Institutional review boards of the participating centres.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement All authors had full access to study data and had final responsibility for the decision to submit.

    • Collaborators The ACTIVE study investigators: Australia – Christopher Fong (Boxhill Hospital, Camberwell, VIC); Jane Zochling (Southern Clinical Research, Hobart, TAS); Peter Yousseff (Royal Prince Alfred Hospital, Camperdown, NSW); Paul Bird (St. George Private Hospital, Miranda, NSW); Nicholas Manolios (Westmead Hospital, Sydney, NSW); and Rob Will (Colin Bayliss Research/Teaching Unit, Victoria Park, WA). Canada – Ben Lasko and Melanie Mason (Manna Research, Toronto, ON); Jude Rodrigues (private practice, Windsor, ON); Alfred Cividino (private practice, Hamilton, ON); Majed Khraishi (Nexus Clinical Research, St. John’s, NL); Arthur Karasik (Arthur Karasik Medicine Professional Corp, Etobicoke, ON); and Louis Bessette (Groupe de Recherche en Maladies Osseuses Inc., Quebec, QC). Czech Republic – Petr Vitek (PV Medical Sro, Zlin); Zuzana Stejfova and Alena Ticha (Revmatologicka Ambulance, Praha); and Katerina Jarosova (Revmatologicky Ustav, Praha). Estonia – Airi Poder (Clinical Research Centre Ltd, Tartu); Andres Pille (East Tallinn Central Hospital, Tallinn); and Jaak Tälli (Innomedica, Tallinn). Hungary – László Sámson (MÁV Kórház és Rendelőintézet, Budapest); Istvan Szombati (Qualiclinic Kft, Budapest); Kiss Csaba (Csolnoky Ferenc Kórház, Veszprém); and Szántó Sándor (Debreceni Egyetem Orvos, Debreceni). New Zealand – Daniel Ching (Timaru Hospital, Timaru); Rajiv Gupta (Middlemore Hospital, Auckland); and Doug White (Rheumatology Clinic, Auckland). Romania – Mariana Pavel (Sf. Apostol Andrei Emergency Clinical County Hospital, Galați); Violeta Bojinca (Sf. Maria Clinical Hospital, Bucharest); Silvia Bojin (Covamed Serv SRL, Sfântu Gheorghe); and Simona Rednic (Cluj-Napoca Emergency Clinical County Hospital, Cluj-Napoca). Russia – Valentin Oleynikov (Penza Regional Clinical Hospital, Penza); Leysan Myasoutova (City Clinical Hospital #7, Kazan); Nikolay Korshunov (Yaroslavl Reg. Clinical Hospital, Yaroslavl); and Diana Krechikova (Dept. Hospital at Smolensk, Smolensk). Spain – Francisco Blanco (Complejo Hospitalario Universitario, Coruña); Antonio Fernandez-Nebro (Hospital General de Málaga, Málaga); Federico Díaz-Gonzalez (Hospital Universitario de Canarias, Santa Cruz de Tenerife); Eduardo Angulo (Hospital de Basurto – Osakidetza, Basurto); Emilio Mola (Hospital Universitario La Paz, Madrid); Jordi Gratacos Masmitja (Corporació Sanitària Parc Taulí, Barcelona); Jesús Rodriguez (Hospital Universitari de Bellvitge, l’Hospitalet de Llobregat); and Agusti Sellas Fernandez (Hospital Universitari Vall d’Hebron, Barcelona). United States – Monika Mohan (Advanced Rheumatology, Lansing, MI); Richard Olson (Rockford Orthopedic Associates, Ltd, Rockford, IL); Carmen Perez-Masuelli (The Clinical Research Institute of Houston, Houston, TX); Jeffrey Alloway (Physicians East, PA, Greenville, NC); Jeffrey Alper (private practice, Naples, FL); Alan J. Kivitz (Altoona Center For Clinical Research, Altoona, PA); Miriam Lara (Palmetto Medical Research, Hialeah, FL); Vipul Joshi (Bay Area Arthritis and Osteoporosis, Brandon, FL); Roger Diegel (Glacier View Research Institute, Kalispell, MT); Tina Bunch (Austin Regional Clinic, Austin, TX); Alfred Felber (Heartland Clinical Research Inc., Augusta, KS); Michael Calmes (Arthritis and Osteoporosis Associates, LLP, Lubbock, TX); David McLain (Achieve Clinical Research, LLC, Birmingham, AL); Robert Holmes (Piedmont Medical Research, LLC, Winston-Salem, NC); John Carter (University of South Florida, Tampa, FL); Farrukh Zaidi (Suncoast Clinical Research, New Port Richey, FL); Maria Greenwald (Desert Medical Advances, Palm Desert, CA); Michael Burnette (Health Point Medical Group, Brandon, FL); Ramesh Gupta (private practice, Memphis, TN); Charles Bradley Franz (Mountain State Clinical Research, Bridgeport, WV); John Cush (Baylor Research Institute, Dallas, TX); Craig Wiesenhutter (Coeur d’Alene Arthritis Clinic, Coeur d’Alene, ID).

    • Author note The results from this study have been published in abstract form: Nash P et al. Early onset of efficacy with apremilast monotherapy in biologic-naïve patients with active psoriatic arthritis: a phase IIIB, randomized, controlled trial [abstract 1703]. Arthritis Rheumatol 2016;68(Suppl 10):2133–4, and Nash P et al. Early onset of efficacy with apremilast monotherapy in biologic-naïve patients with active psoriatic arthritis: a phase IIIB, randomized, controlled trial [abstract OP0219]. Ann Rheum Dis 2017;76(Suppl 2):143.

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