1454 The Journal of Rheumatology 2008; 35:7 Personal non-commercial use only. The Journal of Rheumatology Copyright © 2008. All rights reserved. Drug Use and Toxicity in Psoriatic Disease: Focus on Methotrexate WILLIAMJ.TAYLOR,ELEANORKORENDOWYCH,PETERNASH,PHILIPS.HELLIWELL,ERNESTCHOY, GERALDG.KRUEGER,ENRIQUER.SORIANO,NEILJ.McHUGH,andCHERYLF.ROSEN ABSTRACT. Methotrexate (MTX) toxicity in psoriatic disease was the focus of discussion at the 2007 Annual Meeting of the Group for Research andAssessment of Psoriasis and PsoriaticArthritis (GRAPPA). PlenarypresentationsandresultsofaWeb-basedopinionsurveyofrheumatologistsanddermatolo- gists from GRAPPA, and others from New Zealand,Australia, and Canada, provided topics of dis- cussion for small-group breakout sessions, including hepatotoxicity, alcohol use, fertility and preg- nancy, and combination therapy.As a framework, topics were considered under headings: impor- tance, knowledge deficit, sufficient data for a recommendation, and research agenda. Breakout ses- sion conclusions/consensus were as follows: (1) Data are insufficient to recommend routine serial liver biopsy to prevent MTX-induced liver fibrosis; further research is needed to establish whether serial liver chemistry tests or propeptide of type III collagen can detect hepatotoxicity without the need for liver biopsy. (2) Insufficient data are available to establish a dose-response relationship betweenalcoholuseandMTXhepatotoxicity,sonosafelimitofalcoholintakecanberecommend- ed. (3) Although cessation of MTX 3 months prior to conception is reasonable, inadequate data are availabletospecifydurationortoquantifytheriskofadversefetaloutcome;registriestotrackpreg- nancyoutcomearepotentiallyuseful.(4)Combinationtherapywithanti-TNFagentsorsulfasalazine is safe, but insufficient data are available for combinations with leflunomide or cyclosporine. (J Rheumatol 2008;35:1454–7) Key IndexingTerms: PSORIASIS PSORIATICARTHRITIS METHOTREXATE TOXICITY From the Department of Medicine, University of Otago/Wellington, New Zealand; Royal National Hospital for Rheumatic Diseases, Bath, United Kingdom; Department of Medicine, University of Queensland, Cotton Tree, Australia; Academic Unit of Musculoskeletal Medicine, University of Leeds, Leeds;Academic Department of Rheumatology, King’s College London, United Kingdom; Department of Dermatology, University of Utah, Salt Lake City, Utah, USA; Rheumatology Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; and Division of Dermatology, University ofToronto,TorontoWestern Hospital,Toronto, Ontario, Canada. Supported by an unrestricted financial grant fromAbbott, Centocor, Wyeth, Amgen, and UCB Pharma. W.J.Taylor, PhD, MBChB, FAFRM, FRACP, Department of Medicine, University of Otago/Wellington; E. Korendowych, PhD, MRCP, Royal National Hospital for Rheumatic Diseases; P. Nash, MBBS, FRACP, Department of Medicine, University of Queensland; P.S. Helliwell, MD, PhD, Senior Lecturer in Rheumatology,Academic Unit of Musculoskeletal Medicine, University of Leeds; E. Choy, MD, Reader in Rheumatology, Academic Department of Rheumatology, King’s College London; G.G. Krueger, MD, Department of Dermatology, University of Utah; E.R. Soriano, MD, Rheumatology Unit, Hospital Italiano de Buenos Aires; N.J. McHugh, MBChB, MD, FRCP, FRCPath, Professor in Rheumatology, Royal National Hospital for Rheumatic Diseases; C.F. Rosen, MD, FRCPC, Division of Dermatology, University ofToronto,TorontoWestern Hospital.Address reprint requests to Dr.W.J.Taylor, Department of Medicine, University of Otago/Wellington, PO Box 7343,Wellington, New Zealand; E-mail: will.taylor@otago.ac.nz. MTX. Although many other therapeutic options are now available to patients with psoriasis and PsA, in particular biologic agents such as anti-tumor necrosis factor-α (TNF- α) drugs, MTX remains an important drug. Further, impor- tant differences exist between official recommendations for toxicity monitoring between the dermatology community 2 and the rheumatology community 3 ,whichcanbeconfusing for both practitioners and patients. It was therefore decided that MTX would be an appropriate focus for review by a unique combination of dermatologists and rheumatologists represented at the 2007 Annual Meeting of the Group for ResearchandAssessmentofPsoriasisandPsoriaticArthritis (GRAPPA). One of the intriguing issues with MTX is the difference in toxicities observed between patients with rheumatoid arthritis(RA)comparedtopatientswithpsoriasisorPsA.A recent cross-sectional study confirmed that pulmonary toxi- citywasmorecommoninRApatientscomparedtopatients withPsA,andthathepatotoxicitywasmorecommoninPsA patients 4 . A metaanalysis of longterm MTX treatment stud- iesinRAandpsoriaticdiseaseshoweda3-foldgreaterrisk of hepatic fibrosis in patients with psoriatic disease 5 . The reasons for such differences are unclear, but there may be justification for different toxicity monitoring for patients with psoriatic disease. Priortothemeeting,GRAPPAmembers,aswellasother rheumatologists and dermatologists from Australia, New Despite a weak evidence base, methotrexate (MTX) is one of the most common therapeutic agents for psoriatic arthri- tis (PsA) and has been used in the treatment of severe pso- riasissince1958 1 .Despitereadyavailabilityanddecadesof use in clinical practice, much remains unknown about www.jrheum.org Downloaded on August 1, 2022 from