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ADJUVITE: a double-blind, randomised, placebo-controlled trial of adalimumab in early onset, chronic, juvenile idiopathic arthritis-associated anterior uveitis
  1. Pierre Quartier1,2,3,4,
  2. Amandine Baptiste5,
  3. Véronique Despert6,
  4. Emma Allain-Launay7,
  5. Isabelle Koné-Paut8,
  6. Alexandre Belot4,9,
  7. Laurent Kodjikian10,
  8. Dominique Monnet3,11,
  9. Michel Weber12,
  10. Caroline Elie5,
  11. Bahram Bodaghi13
  12. On behalf of the ADJUVITE Study Group
    1. 1Pediatric Immunology-Hematology and Rheumatology Unit, Necker-Enfants Malades University Hospital, Assistance Publique-Hopitaux de Paris, Paris, France
    2. 2Imagine Institute, Paris, France
    3. 3Paris Descartes University, Paris, France
    4. 4Pediatric Rheumatology and Systemic Auto-immune Diseases, RAISE National Reference Centre, Rennes, France
    5. 5Clinical Research Unit/CIC Paris Descartes, Necker-Enfants Malades-Cochin University Hospital, Paris, France
    6. 6Pediatric Department, Rennes University Hospital, Rennes, France
    7. 7Pediatric Department, University Hospital of Nantes, Nantes, France
    8. 8Pediatric Rheumatology Department, Kremlin-Bicêtre, Assistance Publique-Hopitaux de Paris, University of Paris-Sud, Orsay, France
    9. 9Pediatric Nephrology, Rheumatology, Dermatology, University of Lyon, INSERM U1111, Lyon, France
    10. 10Ophthalmology, Croix-Rousse University Hospital, Lyon, France
    11. 11UMR-CNRS 52, University Hospital Cochin, Assistance Publique-Hopitaux de Paris, Nantes, France
    12. 12Department of Ophthalmology, University Hospital Hotel Dieu, Nantes, France
    13. 13Department of Ophthalmology, University Hospital Pitie-Salpetriere, Paris, France
    1. Correspondence to Professor Pierre Quartier, Pediatric Immunology-Hematology and Rheumatology Unit, Necker-Enfants Malades University hospital, Assistance Publique-Hopitaux de Paris, Paris 75015, France; pierre.quartier{at}nck.aphp.fr

    Abstract

    Objectives To assess the efficacy and safety of adalimumab on uveitis in patients with early onset, chronic, juvenile idiopathic arthritis (JIA)-associated or idiopathic anterior uveitis and an inadequate response to topical steroids and methotrexate (MTX).

    Methods Patients aged 4 years or more with ocular inflammation quantified by laser flare photometry (LFP) ≥30 photon units/ms were double-blindly randomised (1:1) to 2 groups, one treated with placebo and one with adalimumab subcutaneously at a dose of 24 mg/m2 in patients aged <13 years, 40 mg in the others, every other week. The primary outcome was response at month 2 (M2) defined as a 30% reduction of inflammation on LFP in the assessable eye with more severe baseline inflammation and no worsening on slit lamp examination. From M2 to M12, all patients received adalimumab.

    Results At M2, among 31 patients included in intention-to-treat analysis, there were 9/16 responders on adalimumab and 3/15 on placebo (P=0.038, Χ2 test; relative risk=2.81, 95% CI 0.94 to 8.45; risk difference: 36.3%, 95% CI 2.1 to 60.6); there was no significant difference using the Standardised Uveitis Nomenclature classification criteria of improvement. Thirty patients continued the trial after M2 and received adalimumab (open-label phase), 29 reached M12. There were seven serious adverse events none related to study treatment.

    Conclusions This trial is in favour of using adalimumab in patients with early onset, chronic anterior uveitis, which is in most cases associated with JIA, in case of inadequate response to topical therapy and MTX. LFP could be a valuable tool to assess early treatment efficacy.

    Trial registration number NCT01385826.

    • Anti-tnf
    • Juvenile Idiopathic Arthritis
    • Treatment

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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 approved the final manuscript to be submitted and agreed to be accountable for all aspects of the work. Conception and design of the study: PQ, BB. Acquisition of data: PQ, VD, EAL, IK-P, AB, LK, DM, MW, BB and the ADJUVITE Study Group. Analysis and interpretation of data: PQ, AB, CE and BB.

    • Funding Assistance Publique-Hôpitaux de Paris Clinical Research and Development Department (PHRC 2009 01-48).

    • Competing interests PQ has received speakers’s fees (<US$10 000) from AbbVie, Novartis, Pfizer, Roche and SOBI, grants from AbbVie, Pfizer and Novartis, payment for lecture (<US$10 000) from Novartis, personal fees for consultancy (<US$10 000) from AbbVie, Novartis, Novimmune and Sanofi, invitation to congress from AbbVie, BMS, Novartis, Pfizer, Roche and SOBI and has participated as an investigator to clinical trials from AbbVie, BMS, Novartis, Pfizer, Roche and Sanofi. IK-P has received speakers fees (<US$10 000) from AbbVie, Chugai, LFB, Novartis, Pfizer and SOBI, grants from Roche and SOBI, payment for lectures (<US$10 000) from Novartis and SOBI, personal fees for consultancy (<US$10 000) from AbbVie, LFB, Novartis, Novimmune, Pfizer and SOBI, invitation to congress from Novartis and Pfizer and has participated as an investigator to clinical trials from AbbVie, BMS, Novartis, Pfizer, Roche. AB has received invitation to congress from Novartis. LK has received personal fess for consultancy (<US$10 000) from AbbVie, Alcon, Allergan , Bayer, Horus, Novartis, Roche and Théa. DM has received speakers fees (<US$10 000) from AbbVie. MW has participated as an investigator to a clinical trial from AbbVie. BB has received grants from Bayer and Novartis, and personal fees for consultancy (<US$10 000) from AbbVie, Allergan and Santen.

    • Patient consent Obtained.

    • Ethics approval The protocol was approved by the ethics committee ’Comité pour la protection des Personnes Ile de France IV' and by the French agency for security of health products (AFSSAPS) in 2010.

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

    • Collaborators The ADJUVITE Study Group: Brigitte Bader-Meunier, Christelle Bonifas-Rodier, Antoine Brezin, Chloé Couret, Emmanuelle Delair, Marie Desgranges, Agnès Duquesne, Perrine Dusser, Christine Fardeau, Marine Fouillet-Desjonqueres, Caroline Galeotti, Olivier Lebreton, Phuc LeHoang, Candice Meyzer, Richard Mouy, Sylvaine Poignant, Linda Rossi-Semerano, Michaela Semeraro, Soizic Tiriau, Carine H Wouters.

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