Abstract
Objective: To evaluate the efficacy and safety of continuous and paused etanercept regimens in psoriasis patients. Methods: Patients with moderate-to-severe plaque psoriasis were randomized to receive continuous etanercept 25 mg twice weekly or paused etanercept for 54 weeks. The paused group received etanercept 50 mg twice weekly for no more than 12 weeks until reaching a Physician Global Assessment (PGA) of 2 or less (mild or better), when treatment was paused; upon relapse (PGA ≥ 3), etanercept was resumed at 25 mg twice weekly until a PGA of 2 or less was regained. The primary efficacy end point was mean PGA over 54 weeks, which was compared between the continuous and paused groups. Secondary efficacy end points included changes from baseline in mean PGA score, Psoriasis Area and Severity Index (PASI) and patient satisfaction with current psoriasis treatment. Results: Among 711 patients evaluable for efficacy, the mean PGA score averaged over 54 weeks (primary end point) was significantly lower in the continuous etanercept therapy group than in the paused etanercept therapy group (1.98 vs 2.51, respectively; p < 0.001). Mean PGA was significantly reduced from baseline (3.6, both groups) to week 54 in the continuous (1.9) and paused groups (2.4; p < 0.01, within-group comparisons). Mean PASI was significantly decreased from baseline (21.9 and 22.8, respectively) to week 54 with continuous (7.1) and paused therapy (9.5; p < 0.01, within-group comparisons). PASI improved by 68 and 59% from baseline to week 54 in patients receiving continuous and paused etanercept, respectively. Patient satisfaction rates improved from 20.2 and 22.5% in continuous and paused groups, respectively, at baseline to 83.5 and 83.0% at week 12; 83.3 and 78.3% at week 24; and 81.3 and 72.6% at week 54, respectively. Overall, 7.5% (54 out of 720) of patients had serious adverse events (6.4 and 8.5%, continuous and paused groups, respectively); four patients (two per group) had serious infections. No cases of tuberculosis or demyelinating diseases were observed. Conclusion: Both continuous and paused etanercept therapies improved PGA and PASI scores and patient satisfaction rates; patients receiving continuous etanercept therapy showed a greater level of improvement, although those who paused and resumed active treatment generally recaptured response and experienced sustained benefit.
Acknowledgements
The authors would like to thank Joanne Estojak and Kathleen Leach for supporting the study conduct and monitoring and Donna McGuire and Joanne Foehl for assistance with the preparation and review of the manuscript.
In addition to the authors, J-P Ortonne, C Griffiths, E Daudén and R Strohal, CRYSTEL (study 909) investigators included G Stingl, Univ.-Klinik für Dermatologie, Wien, Austria; W Jurecka, Wilhelminenspital der Stadt Wien, Wien, Austria; M de la Brassinne, Centre Hospitalier Universitaire, Liège, Belgium; L Marot, Cliniques Universitaires St-Luc, Bruxelles, Belgium; M Heenen, Hôpital Erasme, Bruxelles, Belgium; J Lambert, UniversitairZiekenhuis Antwerpen, Edegem, Belgium; J-M Naeyaert, Universitaire Ziekenhuis Gent, Gent, Belgium; S Segaert, Universitaire Ziekenhuis St Raphaël, Leuven, Belgium; J Hercogova, Dermatovenerologicka klinika, Praha 8, Czech Republic; K Kragballe, Århus University Hospital, Århus, Denmark; G Jemec, Roskilde Hospital, Roskilde, Denmark; K E Andersen, Odense University Hospita, Odense, Denmark; Ö Tapio Rantanen, Päijät-Hämeen Central Hospital, Ihotautien Klinikka, Lahti, Finland; I Harvima, Kupio University Hospital, Ihotautien Klinikka, Kuopio, Finland; A Claudy, Hopital Edouard Herriot, Lyon, France; J-J Guilhou, Hopital Saint Eloi, Montpellier, France; L Meunier, Hopital Caremeau, Nimes, France; C Beylot, Hopital Haut Leveque, Pessac, France; B Sassolas, Hopital Augustin Morvan, Brest, France; J-F Stalder, Hopital Hotel Dieu, Nantes, France; A Taïeb, Hopital Saint Andre, Bordeaux, France; L Thomas, Hopital Hotel Dieu, Lyon, France; D Lipsker, Hopital Civil, Strasbourg, France; P Saiag, Hopital Ambroise Pare, Boulogne Billancourt, France; M Bagot, Hopital Henri Mondor, Creteil, France; J Bazex, Chu Purpan, Toulouse, France; V Descamps, Hopital Bichat Claude Bernard, Paris, France; G Guillet, Chu La Miletrie, Poitiers, France; P Humbert, Centre Hospitalier Saint Jacques, Besancon, France; D Lambert, Hopital Du Bocage, Dijon, France; P Thomas, Hopital Claude Huriez, Lille, France; F Cambazard, Hopital Nord, Saint-Etienne, France; J-L Schmutz, Hopital Maringer Villemein Fournier, Nancy, France; J-J Grob, Hopital Sainte Marguerite, Marseille, France; P Altmeyer, Ruhr-Universität Bochum, Bochum, Germany; B Bonnekoh, Otto-von-Guericke-Universität Magdeburg, Magdeburg, Germany; M Schön, Universitätsklinik und Poliklinik für Hautkrankheiten, Würzburg, Germany; S Grabbe, Universitätsklinikum Essen, Essen, Germany; U Mrowietz, Universitätsklinikum Kiel, Kiel, Germany; M Röcken, Universitätsklinikum Tübingen, Tübingen, Germany; R Schopf, Universitäts-Hautklinik Mainz, Mainz, Germany; J Simon, Universitätsklinikum Leipzig, Leipzig, Germany; V Streit, Buchholz, Germany; M Augustin, Universitätsklinikum Eppendorf, Hamburg, Germany; R Kaufmann, Klinikum der Universität Frankfurt, Frankfurt, Germany; TA Luger, Klinik und Poliklinik für Dermatologie, Münster, Germany; T Rosenbach, Osnabrück, Germany; B Homey, Uniklinikum Düsseldorf, Düsseldorf, Germany; G Schuler, Dermatologische Klinik mit Poliklinik, Erlangen, Germany; A Katsambas, University of Athens, Athens, Greece; N Stavrianeas, University of Athens, Athens, Greece; F Chrisomallis, University of Thessalonik, Thessalonik, Greece; K Sarolta, Semmelweis University, Budapest, Hungary; A Giannetti, Policlinico di Modena, Modena, Italy; N Aste, Università di Cagliari, Cagliari, Italy; PL Amerio and A Garcovich, Policlinico Gemelli, Roma, Italy; A Peserico and S Piaserico, Università di Padova, Padova, Italy; A Offidani, Università di Ancona Ospedale Regionale di Torrette, Ancona, Italy; Stefano Calvieri, Policlinico Umberto I, Roma, Italy; M Pippione, Ospedale S. Lazzaro, Torino, Italy; M Papini, Università di Terni, Terni, Italy; S Chimenti, Università di ‘Tor Vergata’, Roma, Italy; G Barroni, Policlinico S.Matteo Università di Pavia, Pavia, Italy; G Parovi, Clinica Dermatologica, Genova, Italy; MA de Rie, AMC, Amsterdam Zuidoost, The Netherlands; EMGJ de Jong, UMC St Radboud, Nijmegen, The Netherlands; HB Thio, Erasmus MC, Rotterdam, The Netherlands; TJ Stoof, Vu Medisch Centrum, Amsterdam, The Netherlands; AL Gerretsen, Ijsselland ziekenhuis, Capelle Aan Den Ijssel, The Netherlands; G Lucker, Atrium Medisch Centrum, Heerlen, The Netherlands; CLM Van Hees, Diaconessenhuis Voorburg, Voorburg, The Netherlands; CAFM Bruijnzeel-Koomen, UMC Utrecht, Utrecht, The Netherlands; T Ternowitz, Hudpoliklinikken, Stavanger, Norway; J Öjvind-Holm, Ullevål universitetssykehus, Oslo, Norway; L Rustad, Haukeland universitetssykehus, Bergen, Norway; W Glinski, Klinika Dermatologii AM Instytut Wenerologii, Warszawa, Poland; A Pinto Soares, Hospital Desterro, Lisboa, Portugal; J Cardoso, Hospital Curry Cabral, Lisboa, Portugal; J Diaz Perez, Hospital de Cruces, Bilbao, Spain; A Pérez, Hospital Gral de Valencia, Valencia, Spain; JM Herranz, Hospital Gregorio Marañón, Madrid, Spain; Francisco Vanaclocha, Hospital 12 de Octubre, Madrid, Spain; E Herrera Ceballos, Hospital Clínico Virgen de la Victoria, Malaga, Spain; J Peyri, L´Hospitalet de Llobregat, Barcelona, Spain; C Ferrandiz, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; I-M Bergbrandt, Sahlgrenska Universitetssjukhuset, Göteborg, Sweden; H Beitner, Karolinska Universitetssjukhuset Solna, Stockholm, Sweden; F Nyberg, Danderyds Sjukhus AB, Stockholm, Sweden; O Bäck, Universitetssjukhuset, Lund, Sweden; A Preisler-Häggvisit, Norrlands Universitetssjukhus, Umeå, Sweden; B Stymne, Universitetssjukhuset, Linköping, Sweden; J-H Saurat, University of Geneva, Geneva, Switzerland; N Yawalkar, University of Bern, Bern, Switzerland; A Arnold, University of Basel, Basel, Switzerland; S Serdaroglu, Istanbul Universitesi, Istanbul, Turkey; G Özarmagan, Istanbul Universitesi, Istanbul, Turkey; I Ünal, Ege Üniversitesi Tıp Fakültesi, Bornova-Izmir, Turkey; C Diaz, Birmingham Skin Hospital, Birmingham, UK; R Parslew, Broad Green Hospital, Liverpool, UK; T Chu, Salford Royal Hospitals NHS Trust, Salford, UK; T Cutler, Ipswich Hospital NHS Trust, Ipswich, UK; W Stuart Douglas, Monklands Hospital, Airdrie, UK; P Hutchinson, University Hospitals of Leicester NHS Trust, Leicester, UK; M Rustin, Royal Free Hospital, London, UK; A Anstey, Royal Gwent Hospital, Newport, UK; J Barker, St John’s Institute of Dermatology, London, UK; AY Finlay, University Hospital of Wales, Heath Park, Cardiff, UK; J Berth-Jones, Walsgrave Hospital, Coventry, UK; D Burden, Western Infirmary, Glasgow, UK; A Bewley, Whipps Cross Hospital, London, UK; C Grattan, Norfolk & Norwich University Hospital, Norwich, UK; S Rogers, City of Dublin Skin and Cancer Hospital, Dublin, Ireland; AD Ormerod, Aberdeen Royal Infirmary, Aberdeen, Scotland; M Goodfield, The Leeds Teaching Hospital NHS Trust, Leeds, UK; P Harrison, Royal Lancaster Infirmary, Lancaster, UK.
Financial & competing interests disclosure
Support for this study and medical writing assistance was provided by Wyeth Pharmaceuticals, Collegeville, PA, USA. J-P Ortonne serves as an investigator, speaker and advisor for Schering-Plough, Abbott, Merk-Serono, Centocor, Wyeth, Janssen-Cilag, Meda-Pharma, Pierre-Fabre and Galderma and as an investigator and speaker for Leo-Pharma. C Griffiths is a consultant to and/or in receipt of research grants from, Wyeth, Merck-Serono, Centocor, Abbott, Schering Plough and Novartis. E Daudén is an Advisory Board member and consultant for, has received grants, research support and honoraria for speaking from and has participated in clinical trials for Abbott, Astellas, Biogen, Galderma, Glaxo, Janssen-Cilag, Leo Pharma, Merck-Serono, Novartis, Schering-Plough, Stiefel, Wyeth Pharmaceuticals and 3 M. R Strohal serves on speakers bureaus for Wyeth, Astellas, Lohmann und Rauscher, Meda Pharmaceuticals, Menarini Pharmaceuticals, Stockhausen and Smith & Nephew; has consulting or expert/advisory board agreements with Wyeth, Astellas, Lohmann und Rauscher, Smith & Nephew, Turimed, Helbo Photodynamic Systems, Brial, Pantec Biotechnologies and Actelion; and receives research and educational grants from Stockhausen, 3M-Woundcare, Smith & Nephew, Lohmann und Rauscher and Enjo. D Robertson, R Pedersen, C Molta and B Freundlich are employees of Wyeth Pharmaceuticals.
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Ethical conduct of research
The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.
