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The safety and efficacy of the use of methotrexate in long‐term therapy for rheumatoid arthritis

Joel M. Kremer MD

Corresponding Author

Division of Rheumatology, Albany Medical College, Albany, New York

Department of Radiology, Albany Medical Center Hospital, Albany, New York

Division of Rheumatology, Albany Medical College, Albany, NY 12208
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Joong Kil Lee MD

Division of Rheumatology, Albany Medical College, Albany, New York

Department of Radiology, Albany Medical Center Hospital, Albany, New York

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First published: July 1986
Cited by: 226

Abstract

Twenty‐nine patients participated in a prospective study of the safety and efficacy of oral methotrexate in the treatment of refractory rheumatoid arthritis. Patients received a mean dosage of 12.4 mg weekly over a mean duration of 29.1 months. All patients had liver biopsies at baseline, 2 years, and annually thereafter. Patients improved significantly by all clinical measures of efficacy after 1 month; maximum improvement tended to occur after approximately 6 months of therapy. Radiographs showed improvement of erosive disease in 7 of 11 patients measured. There was a significant reduction in mean prednisone dosage. Four patients required an increase in the dosage of methotrexate after prolonged therapy, because of declining clinical response. Toxicity was noted at some time in 26 of 29 patients (90%), but reactions universally became mild and tolerable after adjustment of the dosage. No significant hepatotoxicity was found in 60 sequential liver biopsies, although elevated transaminase levels were noted at some time in 20 of 29 patients (70%).

Number of times cited according to CrossRef: 226

  • , Association between cumulative methotrexate dose, non‐invasive scoring system and hepatic fibrosis detected by Fibroscan in rheumatoid arthritis patients receiving methotrexate, International Journal of Rheumatic Diseases, 22, 2, (214-221), (2018).
  • , Strategies toward rheumatoid arthritis therapy; the old and the new, Journal of Cellular Physiology, 234, 7, (10018-10031), (2018).
  • , Emerging nanomaterials with advanced drug delivery functions; focused on methotrexate delivery, Coordination Chemistry Reviews, 10.1016/j.ccr.2018.01.007, 359, (32-51), (2018).
  • , Liquid chromatographic methods for the therapeutic drug monitoring of methotrexate as clinical decision support for personalized medicine: A brief review, Biomedical Chromatography, 32, 5, (2018).
  • , Investigating methotrexate toxicity within a randomized double-blinded, placebo-controlled trial: Rationale and design of the Cardiovascular Inflammation Reduction Trial-Adverse Events (CIRT-AE) Study, Seminars in Arthritis and Rheumatism, 10.1016/j.semarthrit.2017.02.003, 47, 1, (133-142), (2017).
  • , Discoveries of conventional synthetic disease modifying anti-rheumatic drugs – Serendipity or flawless reasoning?, Indian Journal of Rheumatology, 11, 1, (32), (2016).
  • , Liver cirrhosis in selected autoimmune diseases: a nationwide cohort study in Taiwan, Rheumatology International, 36, 2, (199), (2016).
  • , Landmark papers on the discovery of methotrexate for the treatment of rheumatoid arthritis and other systemic inflammatory rheumatic diseases: a fascinating story, International Journal of Rheumatic Diseases, 19, 9, (844-851), (2016).
  • , Skin Signs of Rheumatoid Arthritis and its Therapy-Induced Cutaneous Side Effects, American Journal of Clinical Dermatology, 10.1007/s40257-015-0167-z, 17, 2, (147-162), (2015).
  • , Methotrexate inhibits osteoclastogenesis by decreasing RANKL-induced calcium influx into osteoclast progenitors, Journal of Bone and Mineral Metabolism, 10.1007/s00774-015-0702-2, 34, 5, (526-531), (2015).
  • , The Skin and Disorders of the Musculoskeletal System, Rook's Textbook of Dermatology, Ninth Edition, (1-20), (2016).
  • , Neutropenia in the Elderly: A Rheumatology Perspective, Drugs & Aging, 10.1007/s40266-016-0383-0, 33, 8, (585-601), (2016).
  • , Two Cases of Rheumatoid Nodules Developing on the Fingers in Patients with Rheumatoid Arthritis, Nishi Nihon Hifuka, 78, 4, (362), (2016).
  • , Utilization of Subcutaneous Methotrexate in Rheumatoid Arthritis Patients After Failure or Intolerance to Oral Methotrexate: A Multicenter Cohort Study, Advances in Therapy, 10.1007/s12325-015-0276-3, 33, 1, (46-57), (2016).
  • , Rheumatoid Arthritis, Compendium of Inflammatory Diseases, 10.1007/978-3-7643-8550-7_205, (1159-1168), (2016).
  • , Sex Differences in mRNA Expression of Reduced Folate Carrier‐1, Folypolyformyl Glutamate Synthase, and γ‐Glutamyl Hydrolase in a Healthy Japanese Population, The Journal of Clinical Pharmacology, 56, 12, (1563-1569), (2016).
  • , Expression of anti‐Porphyromonas gingivalis peptidylarginine deiminase immunoglobulin G and peptidylarginine deiminase‐4 in patients with rheumatoid arthritis and periodontitis, Journal of Periodontal Research, 51, 1, (103-111), (2015).
  • , A Study to Evaluate the Safety, Tolerability, and Efficacy of Brodalumab in Subjects with Rheumatoid Arthritis and an Inadequate Response to Methotrexate, The Journal of Rheumatology, 10.3899/jrheum.141271, 42, 6, (912-919), (2015).
  • , Subcutaneous nodules are associated with cardiovascular events in patients with rheumatoid arthritis: results from a large US registry, Clinical Rheumatology, 34, 10, (1697), (2015).
  • , Granulomatous Drug Eruptions, Dermatologic Clinics, 33, 3, (525), (2015).
  • , Efficacy and safety of ascending methotrexate dose in combination with adalimumab: the randomised CONCERTO trial, Annals of the Rheumatic Diseases, 10.1136/annrheumdis-2013-204769, 74, 6, (1037-1044), (2014).
  • , Methotrexate-associated lymphoproliferative disorders of the tongue developing in patients with rheumatoid arthritis: a report of 2 cases and a review, Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 10.1016/j.oooo.2014.04.002, 119, 1, (e1-e5), (2015).
  • , Methotrexate in the treatment of arthritis, Nursing and Residential Care, 16, 9, (492), (2014).
  • , Clinical, Functional, and Radiographic Implications of Time to Treatment Response in Patients With Early Rheumatoid Arthritis: a Posthoc Analysis of the PREMIER Study, The Journal of Rheumatology, 10.3899/jrheum.121468, 41, 2, (235-243), (2013).
  • , Determinants of Erythrocyte Methotrexate Polyglutamate Levels in Rheumatoid Arthritis, The Journal of Rheumatology, 10.3899/jrheum.131290, 41, 11, (2167-2178), (2014).
  • , Clinical disease activity and acute phase reactant levels are discordant among patients with active rheumatoid arthritis: acute phase reactant levels contribute separately to predicting outcome at one year, Arthritis Research & Therapy, 10.1186/ar4469, 16, 1, (R40), (2014).
  • , Methotrexate Induced Pancytopenia, Case Reports in Rheumatology, 10.1155/2014/679580, 2014, (1-4), (2014).
  • , Genetic polymorphisms in low-dose methotrexate transporters: current relevance as methotrexate therapeutic outcome biomarkers, Pharmacogenomics, 10.2217/pgs.14.116, 15, 12, (1611-1635), (2014).
  • , Periodontal Treatment Decreases Levels of Antibodies to Porphyromonas gingivalis and Citrulline in Patients With Rheumatoid Arthritis and Periodontitis, Journal of Periodontology, 84, 12, (e74-e84), (2013).
  • , Rheumatoid Lung Disease, Organizing Pneumonia, and the Pathology of Pulmonary Drug Toxicity, Pathology Case Reviews, 18, 3, (120), (2013).
  • , Multinational evidence-based World Association of Sarcoidosis and Other Granulomatous Disorders recommendations for the use of methotrexate in sarcoidosis, Current Opinion in Pulmonary Medicine, 19, 5, (545), (2013).
  • , Hepatotoxicity Related to Methotrexate, Drug-Induced Liver Disease, 10.1016/B978-0-12-387817-5.00032-7, (593-604), (2013).
  • , Genetic risk factors for drug-induced liver injury in rheumatoid arthritis patients using low-dose methotrexate, Pharmacogenomics, 10.2217/pgs.12.183, 14, 1, (63-73), (2013).
  • , The use of ‘off-the-shelf’ foot orthoses in the reduction of foot symptoms in patients with early rheumatoid arthritis, The Foot, 23, 4, (123), (2013).
  • , Validation of the Methotrexate‐First Strategy in Patients With Early, Poor‐Prognosis Rheumatoid Arthritis: Results From a Two‐Year Randomized, Double‐Blind Trial, Arthritis & Rheumatism, 65, 8, (1985-1994), (2013).
  • , Severity index for rheumatoid arthritis and its association with health care costs and biologic therapy use in Turkey, Health Economics Review, 10.1186/2191-1991-3-5, 3, 1, (5), (2013).
  • , Copper-Catalyzed N- and O-Alkylation of Amines and Phenols using Alkylborane Reagents, Organic Letters, 15, 7, (1544), (2013).
  • , Etanercept, Therapeutic Fc‐Fusion Proteins, (255-282), (2013).
  • , The Skin and Rheumatic Diseases, Kelley's Textbook of Rheumatology, 10.1016/B978-1-4377-1738-9.00043-8, (599-616), (2013).
  • , PARS PLANA AHMED VALVE AND VITRECTOMY IN PATIENTS WITH GLAUCOMA ASSOCIATED WITH POSTERIOR SEGMENT DISEASE, Retina, 33, 10, (2059), (2013).
  • , Determination of erythrocyte methotrexate polyglutamates by liquid chromatography/tandem mass spectrometry after low-dose methotrexate therapy in Chinese patients with rheumatoid arthritis, Journal of Chromatography B, 10.1016/j.jchromb.2012.08.032, 907, (41-48), (2012).
  • , Differential Gene Expression Profiles May Differentiate Responder and Nonresponder Patients with Rheumatoid Arthritis for Methotrexate (MTX) Monotherapy and MTX Tumor Necrosis Factor Inhibitor Combined Therapy, The Journal of Rheumatology, 10.3899/jrheum.120092, 39, 8, (1524-1532), (2012).
  • , Extraartikuläre Manifestationen der rheumatoiden ArthritisExtra-articular manifestations of rheumatoid arthritis, Zeitschrift für Rheumatologie, 10.1007/s00393-011-0928-x, 71, 10, (841-849), (2012).
  • , Evolution of treatment for rheumatoid arthritis, Rheumatology, 10.1093/rheumatology/kes278, 51, suppl 6, (vi28-vi36), (2012).
  • , Current and future role of methotrexate in the therapeutic armamentarium for rheumatoid arthritis, International Journal of Clinical Rheumatology, 10.2217/ijr.12.10, 7, 2, (179-189), (2012).
  • , Cost‐effectiveness of biologic response modifiers compared to disease‐modifying antirheumatic drugs for rheumatoid arthritis: A systematic review, Arthritis Care & Research, 63, 1, (65-78), (2010).
  • , Methotrexate: Optimizing the Efficacy in Rheumatoid Arthritis, Therapeutic Advances in Musculoskeletal Disease, 10.1177/1759720X11408635, 3, 3, (151-158), (2011).
  • , Évaluation de la fibrose hépatique par élastométrie chez les patients atteints de polyarthrite rhumatoïde traités par méthotrexate, Revue du Rhumatisme, 78, 1, (47), (2011).
  • , Extra-articular manifestations of rheumatoid arthritis: An update, Autoimmunity Reviews, 10.1016/j.autrev.2011.09.001, 11, 2, (123-131), (2011).
  • , Skin in rheumatic disease, Rheumatology, 10.1016/B978-0-323-06551-1.00032-4, (285-295), (2011).
  • , Leukoencephalopathy Induced by Low-dose Methotrexate in a Patient with Rheumatoid Arthritis, Internal Medicine, 10.2169/internalmedicine.50.5552, 50, 19, (2219-2222), (2011).
  • , Biologic Foundations for Skeletal Tissue Engineering, Synthesis Lectures on Tissue Engineering, 10.2200/S00329ED1V01Y201101TIS007, 3, 1, (1-220), (2011).
  • , Assessment of liver fibrosis by transient elastography in rheumatoid arthritis patients treated with methotrexate, Joint Bone Spine, 77, 6, (588), (2010).
  • , Assessment of liver fibrosis with transient elastography and FibroTest in patients treated with methotrexate for chronic inflammatory diseases: A case–control study, Journal of Hepatology, 53, 6, (1035), (2010).
  • , Non-Infectious Granulomatous Diseases of the Skin and their Associated Systemic Diseases, American Journal of Clinical Dermatology, 10.2165/11530080-000000000-00000, 11, 3, (171-181), (2010).
  • , Measurement of Erythrocyte Methotrexate Polyglutamate Levels: Ready for Clinical Use in Rheumatoid Arthritis?, Current Rheumatology Reports, 10.1007/s11926-010-0120-3, 12, 5, (342-347), (2010).
  • , A novel treatment for rheumatoid nodules (RN) with intralesional fluorouracil, International Journal of Dermatology, 48, 5, (543-546), (2009).
  • , The Efficacy of Disease Modifying Anti-Rheumatic Drugs in Rheumatoid Arthritis in Local Patients of Karachi, Pakistan Journal of Biological Sciences, 10.3923/pjbs.2009.339.345, 12, 4, (339-345), (2009).
  • , Role and place of methotrexate in vasculitis management, International Journal of Clinical Rheumatology, 10.2217/ijr.09.52, 4, 6, (697-715), (2009).
  • , Prospective study of methotrexate treatment for rheumatoid arthritis treated legitimately according to the government recommended 8 mg/week dose, Modern Rheumatology, 10.3109/s10165-009-0205-x, 19, 6, (637-642), (2014).
  • , Biologic therapy of rheumatoid arthritis, Srpski arhiv za celokupno lekarstvo, 10.2298/SARH0904205D, 137, 3-4, (205-210), (2009).
  • , Prospective study of methotrexate treatment for rheumatoid arthritis treated legitimately according to the government recommended 8 mg/week dose, Modern Rheumatology, 10.1007/s10165-009-0205-x, 19, 6, (637-642), (2009).
  • , Methotrexate treatment of rheumatic diseases: Can we do better?, Arthritis & Rheumatism, 58, 11, (3279-3282), (2008).
  • , Pharmacokinetics of oral methotrexate in patients with rheumatoid arthritis, Arthritis & Rheumatism, 58, 11, (3299-3308), (2008).
  • , Foie et méthotrexate, Gastroentérologie Clinique et Biologique, 32, 2, (134), (2008).
  • , Results of a two‐year followup study of patients with rheumatoid arthritis who received a combination of abatacept and methotrexate, Arthritis & Rheumatism, 58, 4, (953-963), (2008).
  • , Methotrexate in rheumatoid arthritis, Expert Review of Clinical Immunology, 10.1586/1744666X.3.1.27, 3, 1, (27-33), (2014).
  • , Next-generation calcineurin inhibitors for ophthalmic indications, Expert Opinion on Investigational Drugs, 16, 10, (1525), (2007).
  • , Rheumatoid Nodule, Seminars in Cutaneous Medicine and Surgery, 26, 2, (100), (2007).
  • , Exploratory analysis of four polymorphisms in human GGH and FPGS genes and their effect in methotrexate-treated rheumatoid arthritis patients , Pharmacogenomics, 10.2217/14622416.8.2.141, 8, 2, (141-150), (2007).
  • , Diffuse Lung Disease, Evidence‐based Respiratory Medicine, (491-508), (2007).
  • , Durability of treatment with methotrexate in Venezuelan patients with rheumatoid arthritis, Rheumatology International, 10.1007/s00296-006-0261-x, 27, 6, (531-536), (2006).
  • , Massive myelinolytic leukoencephalopathy in a patient medicated with low-dose oral methotrexate for rheumatoid arthritis: an autopsy report, Acta Neuropathologica, 10.1007/s00401-007-0214-9, 114, 4, (425-430), (2007).
  • , Efficacy and safety of bucillamine, ad-penicillamine analogue, in patients with active rheumatoid arthritis, Modern Rheumatology, 16, 2, (85), (2006).
  • , Pancytopenia After Low Dose Methotrexate Therapy in a Hemodialysis Patient: Case Report and Review of Literature, Renal Failure, 28, 1, (95), (2006).
  • , Removal of Methotrexate by Peritoneal Dialysis and Hemodialysis in a Single Patient with End-Stage Renal Disease, The American Journal of the Medical Sciences, 332, 3, (156), (2006).
  • , Noninfectious Granulomatous Diseases: An Update, Advances in Dermatology, 22, (31), (2006).
  • , Risk genotypes in folate‐dependent enzymes and their association with methotrexate‐related side effects in rheumatoid arthritis, Arthritis & Rheumatism, 54, 2, (607-612), (2006).
  • , Rheumatoid nodulosis during methotrexate therapy in a patient with rheumatoid arthritis, Modern Rheumatology, 16, 6, (401), (2006).
  • , Pharmacogenomic and metabolic biomarkers in the folate pathway and their association with methotrexate effects during dosage escalation in rheumatoid arthritis, Arthritis & Rheumatism, 54, 10, (3095-3103), (2006).
  • , Efficacy and safety of bucillamine, a d-penicillamine analogue, in patients with active rheumatoid arthritis, Modern Rheumatology, 10.1007/s10165-005-0466-y, 16, 2, (85-91), (2006).
  • , Rheumatoid nodulosis during methotrexate therapy in a patient with rheumatoid arthritis, Modern Rheumatology, 10.1007/s10165-006-0522-2, 16, 6, (401-403), (2006).
  • , Treatment of rheumatoid arthritis, American Journal of Health-System Pharmacy, 10.2146/ajhp050514, 63, 24, (2451-2465), (2006).
  • , Rheumatoid arthritis: A review of the cutaneous manifestations, Journal of the American Academy of Dermatology, 10.1016/j.jaad.2004.07.023, 53, 2, (191-209), (2005).
  • , Efficacy and Toxicity Profile of Methotrexate Chloroquine Combination in Treatment of Active Rheumatoid Arthritis, Medical Journal Armed Forces India, 61, 1, (29), (2005).
  • , Methotrexate dosage reduction in patients with rheumatoid arthritis beginning therapy with infliximab: the Infliximab Rheumatoid Arthritis Methotrexate Tapering (iRAMT) trial, Current Medical Research and Opinion, 10.1185/030079905X53261, 21, 8, (1181-1190), (2005).
  • , Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase, and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis, Arthritis & Rheumatism, 50, 9, (2766-2774), (2004).
  • , Toward a better understanding of methotrexate, Arthritis & Rheumatism, 50, 5, (1370-1382), (2004).
  • , Dose escalation of parenteral methotrexate in active rheumatoid arthritis that has been unresponsive to conventional doses of methotrexate: A randomized, controlled trial, Arthritis & Rheumatism, 50, 2, (364-371), (2004).
  • , Drug-Induced Respiratory Disease in Connective Tissue Diseases, Pulmonary involvement in systemic autoimmune diseases, 10.1016/S1571-5078(04)02013-6, (245-294), (2004).
  • , Self-resolution of Epstein-Barr virus–associated B-cell lymphoma in a patient with dermatomyositis following withdrawal of mycophenolate mofetil and methotrexate, Journal of the American Academy of Dermatology, 51, 2, (124), (2004).
  • , A giant rheumatoid nodule, Clinical Rheumatology, 10.1007/s10067-004-0926-3, 23, 5, (467-469), (2004).
  • , Tacrolimus in rheumatoid arthritis patients receiving concomitant methotrexate, Arthritis & Rheumatism, 48, 10, (2763-2768), (2003).
  • , Adalimumab, a fully human anti–tumor necrosis factor α monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: The ARMADA trial, Arthritis & Rheumatism, 48, 1, (35-45), (2003).
  • , Efficacy and safety of tacrolimus in patients with rheumatoid arthritis: A double‐blind trial, Arthritis & Rheumatism, 48, 12, (3328-3337), (2003).
  • , Nodulosis acelerada por metotrexato en un paciente con artritis reumatoide y síndrome de Sjögren, Actas Dermo-Sifiliográficas, 94, 7, (470), (2003).
  • , Methotrexate-Induced Pulmonary Injury: Serial CT findings, Journal of Thoracic Imaging, 10.1097/00005382-200310000-00004, 18, 4, (231-236), (2003).
  • , A Review of Methotrexate‐Induced Accelerated Nodulosis, Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 22, 9, (1157-1162), (2012).
  • , Radiographic outcome after three years of patients with early erosive rheumatoid arthritis treated with intramuscular methotrexate or parenteral gold. Extension of a one‐year double‐blind study in 174 patients, Rheumatology, 41, 2, (196), (2002).
  • , The HLA-DRB1*0401 Allele and the Development of Methotrexate-Induced Accelerated Rheumatoid Nodulosis, Medicine, 10.1097/00005792-200107000-00006, 80, 4, (271-278), (2001).
  • , Old and New Drugs Used in Rheumatoid Arthritis: A Historical Perspective, American Journal of Therapeutics, 10.1097/00045391-200103000-00007, 8, 2, (123-143), (2001).
  • , Use of methotrexate in the management of sight-threatening uveitis, Ocular Immunology and Inflammation, 9, 1, (35), (2001).
  • , Comparative Tolerability of Treatments for Inflammatory Bowel Disease, Drug Safety, 23, 5, (429), (2000).
  • , Effect of methotrexate on the temporomandibular joint and facial morphology in juvenile rheumatoid arthritis patients, American Journal of Orthodontics and Dentofacial Orthopedics, 118, 1, (75), (2000).
  • , A Comparison of Etanercept and Methotrexate in Patients with Early Rheumatoid Arthritis, New England Journal of Medicine, 343, 22, (1586), (2000).
  • , Infliximab and Methotrexate in the Treatment of Rheumatoid Arthritis, New England Journal of Medicine, 343, 22, (1594), (2000).
  • , Colchicine Therapy for Low‐Dose‐Methotrexate‐Induced Accelerated Nodulosis in a Rheumatoid Arthritis Patient, The Journal of Dermatology, 26, 10, (691-694), (2015).
  • , Long-term methotrexate (MTX) combination therapy versus MTX alone for active rheumatoid arthritis, Japanese Journal of Rheumatology, 10.3109/BF03041257, 9, 1, (31-44), (2014).
  • , Methotrexate produces delayed emesis in dogs: a potential model of delayed emesis induced by chemotherapy, European Journal of Pharmacology, 372, 3, (261), (1999).
  • , A Trial of Etanercept, a Recombinant Tumor Necrosis Factor Receptor:Fc Fusion Protein, in Patients with Rheumatoid Arthritis Receiving Methotrexate, New England Journal of Medicine, 10.1056/NEJM199901283400401, 340, 4, (253-259), (1999).
  • , Long-term methotrexate (MTX) combination therapy versus MTX alone for active rheumatoid arthritis, Japanese Journal of Rheumatology, 10.1007/BF03041257, 9, 1, (31-44), (1999).
  • , Leukocytoclastic vasculitis induced by low‐dose methotrexate: in vitro evidence for an immunologic mechanism, Journal of the European Academy of Dermatology and Venereology, 10, 1, (81-85), (2006).
  • , Combination therapy with biologic agents in rheumatoid arthritis: Perils and promise, Arthritis & Rheumatism, 41, 9, (1548-1551), (2004).
  • , Long-term exposure to methotrexate induces immunophenotypic changes, decreased methotrexate uptake and increased dihydrofolate gene copy number in jurkat T cells, International Journal of Immunopharmacology, 19, 11-12, (709), (1998).
  • , Accelerated cutaneous nodulosis during methotrexate therapy in a patient with rheumatoid arthritis, Journal of the American Academy of Dermatology, 10.1016/S0190-9622(98)70390-1, 39, 2, (359-362), (1998).
  • , METHOTREXATE AND EMERGING THERAPIES, Rheumatic Disease Clinics of North America, 24, 3, (651), (1998).
  • , The population pharmacokinetics of long‐term methotrexate in rheumatoid arthritis, British Journal of Clinical Pharmacology, 46, 4, (369-376), (2003).
  • , Safty, efficacy, and mortality in a long‐term cohort of patients with rheumatoid arthritis taking methotrexate: Folloup after a mean of 13.3 years, Arthritis & Rheumatism, 40, 5, (984-985), (2005).
  • , THE REMARKABLE SPECTRUM OF METHOTREXATE TOXICITIES, Rheumatic Disease Clinics of North America, 23, 4, (939), (1997).
  • , STEROID-SPARING ALTERNATIVE TREATMENTS FOR SARCOIDOSIS, Clinics in Chest Medicine, 18, 4, (853), (1997).
  • , Lymphoma in patients with rheumatoid arthritis: Association with the disease state or methotrexate treatment with the disease state or methotrexate treatment, Seminars in Arthritis and Rheumatism, 26, 6, (794), (1997).
  • , Clinical, laboratory, radiographic, and histopathologic features of methotrexate‐associated lung injury in patients with rheumatoid arthritis. A multicenter study with literature review, Arthritis & Rheumatism, 40, 10, (1829-1837), (2005).
  • , Measures of activity and damage in rheumatoid arthritis: Depiction of changes and prediction of mortality over five years, Arthritis & Rheumatism, 10, 6, (381-394), (2005).
  • , METHOTREXATE PULMONARY TOXICITY, Rheumatic Disease Clinics of North America, 23, 4, (917), (1997).
  • , Methotrexate, Clinics in Dermatology, 15, 5, (781), (1997).
  • , Liver biopsy findings in patients with juvenile rheumatoid arthritis receiving long-term, weekly methotrexate therapy, The Journal of Pediatrics, 128, 1, (149), (1996).
  • , The cost‐effectiveness of liver biopsy in rheumatoid arthritis patients treated with methotrexate, Arthritis & Rheumatism, 38, 3, (326-333), (2005).
  • , Serious adverse events with low-dose, long-term corticosteroid therapy in rheumatoid arthritis, The American Journal of Medicine, 99, 6, (692), (1995).
  • , Every‐other‐week methotrexate in patients with rheumatoid arthritis, Arthritis & Rheumatism, 38, 5, (601-607), (2005).
  • , Infections during low-dose methotrexate treatmentin rheumatoid arthritis, Seminars in Arthritis and Rheumatism, 24, 6, (411), (1995).
  • , Experience with low-dose methotrexate: Toxicity, tolerability and effect on conventional patterns of drug therapy for inflammatory arthritis, Clinical Rheumatology, 10.1007/BF02208152, 14, 5, (544-550), (1995).
  • , Low-dose methotrexate in rheumatic diseases—Efficacy, side effects, and risk factors for side effects, Seminars in Arthritis and Rheumatism, 23, 5, (310), (1994).
  • , Methotrexate, Clinical Immunotherapeutics, 1, 3, (217), (1994).
  • , Effect of Three Lipophilic Methotrexate Derivatives Upon Mediator Release by Lipopolysaccharide‐stimulated Rat Peritoneal Macrophages, Journal of Pharmacy and Pharmacology, 46, 4, (291-295), (2011).
  • , Methotrexate for Rheumatoid Arthritis, Arthritis & Rheumatism, 37, 3, (316-328), (2005).
  • , Effect of liposomally encapsulated MTX-DMPE conjugates upon TNFα and PGE2 release by lipopolysaccharide stimulated rat peritoneal macrophages, Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1225, 2, (217), (1994).
  • , Serum levels of interleukin‐6 and tumour‐necrosis‐factor‐alpha are not correlated to disease activity in patients with rheumatoid arthritis after treatment with low‐dose methotrexate, European Journal of Clinical Investigation, 24, 1, (73-75), (2008).
  • , Prostaglandin and tumor necrosis factor secretion by peritoneal macrophages isolated from normal and arthritic rats treated with liposomal methotrexate, Journal of Pharmacological and Toxicological Methods, 32, 1, (53), (1994).
  • , Microheterogeneity of alpha 1-acid glycoprotein in patients with rheumatoid arthritis., Annals of the Rheumatic Diseases, 10.1136/ard.53.7.480-a, 53, 7, (480-480), (1994).
  • , Augmented expression of inflammatory cytokines and adhesion molecules in accelerated nodulosis during methotrexate therapy., Annals of the Rheumatic Diseases, 10.1136/ard.53.7.480-b, 53, 7, (480-481), (1994).
  • , Methotrexate-related pulmonary complications in patients with rheumatoid arthritis: cluster of five cases in a period of three months., Annals of the Rheumatic Diseases, 10.1136/ard.53.7.479, 53, 7, (479-480), (1994).
  • , Nonperipheral accelerated nodulosis in a methotrexate‐treated rheumatoid arthritis patient, Arthritis & Rheumatism, 36, 1, (132-133), (2005).
  • , Antirheumatic drug reactions in the lung, Baillière's Clinical Rheumatology, 7, 1, (147), (1993).
  • , The effects of drug therapy on radiographic progression of rheumatoid arthritis. results of a 36‐week randomized trial comparing methotrexate and auranofin, Arthritis & Rheumatism, 36, 5, (613-619), (2005).
  • , Radiographic assessment of disease progression in rheumatoid arthritis patients enrolled in the cooperative systematic studies of the rheumatic diseases program randomized clinical trial of methotrexate, auranofin, or a combination of the two, Arthritis & Rheumatism, 36, 10, (1364-1369), (2005).
  • , Reversible Lymphomas Associated with Epstein-Barr Virus Occurring during Methotrexate Therapy for Rheumatoid Arthritis and Dermatomyositis, New England Journal of Medicine, 328, 18, (1317), (1993).
  • , Effects of administration of an anti‐cd5 immunoconjugate in rheumatoid arthritis. results of two phase ii studies, Arthritis & Rheumatism, 36, 5, (620-630), (2005).
  • , Pneumonitis Complicating Low-dose Methotrexate Therapy for Rheumatoid Arthritis, Chest, 104, 5, (1620), (1993).
  • , Intestinal absorption in patients with rheumatoid arthritis treated with methotrexate, Clinical Rheumatology, 10.1007/BF02231531, 12, 2, (223-225), (1993).
  • , One year treatment with low dose methotrexate in rheumatoid arthritis: Effect on class specific rheumatoid factors, Clinical Rheumatology, 10.1007/BF02231579, 12, 3, (357-360), (1993).
  • , Methotrexate in Resistant Juvenile Rheumatoid Arthritis, New England Journal of Medicine, 326, 16, (1043), (1992).
  • , Timed treatment of the arthritic diseases: a review and hypothesis, Seminars in Arthritis and Rheumatism, 22, 2, (83), (1992).
  • , The effect of food on the absorption of methotrexate sodium tablets in healthy volunteers, Arthritis & Rheumatism, 35, 7, (761-764), (2005).
  • , Benefit of G-CSF for methotrexate-induced neutropenia in rheumatoid arthritis, The American Journal of Medicine, 92, 3, (337), (1992).
  • , The treatment of wegener's granulomatosis with glucocorticoids and methotrexate, Arthritis & Rheumatism, 35, 11, (1322-1329), (2014).
  • , Immunosupressive therapy for primary biliary cirrhosis, Journal of Hepatology, 14, 1, (1), (1992).
  • , Treatment of rheumatoid arthritis, Postgraduate Medicine, 91, 1, (285), (1992).
  • , Morbidity associated with long-term methotrexate therapy in juvenile rheumatoid arthritis, The Journal of Pediatrics, 120, 3, (468), (1992).
  • , Long‐Term Prospective Study of Methotrexate in the Treatment of Rheumatoid Arthritis, Arthritis & Rheumatism, 35, 2, (129-137), (2005).
  • , Synthesis of methotrexate-dimyristoylphosphatidylethanolamine analogs and characterization of methotrexate release in vitro, International Journal of Pharmaceutics, 85, 1-3, (189), (1992).
  • , Long‐Term Prospective Study of the Use of Methotrexate in the Treatment of Rheumatoid Arthritis, Arthritis & Rheumatism, 35, 2, (138-145), (2005).
  • , Molecular mechanism of methotrexate action in inflammation, Inflammation, 10.1007/BF00918968, 16, 5, (411-423), (1992).
  • , Induction of remission in a patient with Takayasu's arteritis by low dose pulses of methotrexate., Annals of the Rheumatic Diseases, 10.1136/ard.51.7.904, 51, 7, (904-905), (1992).
  • , Recombinant human interferon gamma in the treatment of rheumatoid arthritis: double blind placebo controlled study., Annals of the Rheumatic Diseases, 10.1136/ard.51.9.1039, 51, 9, (1039-1043), (1992).
  • , Acute pneumonitis associated with low dose methotrexate treatment for rheumatoid arthritis: report of five cases and review of published reports., Thorax, 10.1136/thx.47.8.628, 47, 8, (628-633), (1992).
  • , Hepatotoxicity in a rat model caused by orally administered methotrexate, Hepatology, 14, 5, (906-910), (2005).
  • , Herpes zoster in patients with rheumatoid arthritis treated with weekly, low-dose methotrexate, The American Journal of Medicine, 90, 3, (295), (1991).
  • , Herpes zoster in patients with rheumatoid arthritis treated with weekly, low-dose methotrexate, The American Journal of Medicine, 90, 1, (295), (1991).
  • , Methotrexate and histologic hepatic abnormalities: A meta-analysis, The American Journal of Medicine, 90, 1, (711), (1991).
  • , Retardation of Radiologic Progression in Rheumatoid Arthritis With Methotrexate Therapy. A Controlled Study, Arthritis & Rheumatism, 34, 10, (1236-1244), (2005).
  • , A double-blind comparison of parenteral methotrexate and parenteral gold in the treatment of early erosive rheumatoid arthritis: An interim report on 102 patients after 12 months, Seminars in Arthritis and Rheumatism, 10.1016/0049-0172(91)90047-4, 21, 2, (13-20), (1991).
  • , Local infectious complications following large joint replacement in rheumatoid arthritis patients treated with methotrexate versus those not treated with methotrexate, Arthritis & Rheumatism, 34, 2, (146-152), (2005).
  • , Methotrexate and histologic hepatic abnormalities: A meta-analysis, The American Journal of Medicine, 90, 6, (711), (1991).
  • , Long-term methotrexate therapy for rheumatoid arthritis, Seminars in Arthritis and Rheumatism, 20, 5, (317), (1991).
  • , Two methods of assessment of methotrexate hepatotoxicity in patients with rheumatoid arthritis., Annals of the Rheumatic Diseases, 10.1136/ard.50.7.471, 50, 7, (471-476), (1991).
  • , Resolve: Methotrexate is the drug of choice after NSAIDs in rheumatoid arthritis, Seminars in Arthritis and Rheumatism, 20, 2, (76), (1990).
  • , THERAPEUTIC PROGRESS–REVIEW XXXVII: METHOTREXATE–AN IMMUNOMODULATOR WITH EXPANDING INDICATIONS, Journal of Clinical Pharmacy and Therapeutics, 15, 2, (89-95), (2008).
  • , Clinical and Laboratory Outcomes during the Treatment of Rheumatoid Arthritis with Methotrexate, Scandinavian Journal of Rheumatology, 19, 4, (285), (1990).
  • , The effect of folic acid supplementation on the toxicity of low‐dose methotrexate in patients with rheumatoid arthritis, Arthritis & Rheumatism, 33, 1, (9-18), (2005).
  • , The risks of antimalarial retinopathy, azathioprine lymphoma and methotrexate hepatotoxicity during the treatment of rheumatoid arthritis, Baillière's Clinical Rheumatology, 4, 2, (193), (1990).
  • , Health status reports in the care of patients with rheumatoid arthritis, Journal of Clinical Epidemiology, 43, 11, (1243), (1990).
  • , Methotrexate—the rapidly acting drug, Baillière's Clinical Rheumatology, 4, 3, (575), (1990).
  • , Toxicité neurologique sous méthotrexate à faible dose, La Revue de Médecine Interne, 11, 2, (184), (1990).
  • , Proposition: Methotrexate should not be the first second-line agent to be used in rheumatoid arthritis if NSAIDs fail, Seminars in Arthritis and Rheumatism, 20, 2, (69), (1990).
  • , Pulmonary complications of antirheumatic drug therapy, Seminars in Arthritis and Rheumatism, 19, 6, (353), (1990).
  • , Aspirin, hydroxychloroquine, and hepatic enzyme abnormalities with methotrexate in rheumatoid arthritis, Arthritis & Rheumatism, 33, 11, (1611-1619), (2005).
  • , Can treatment with methotrexate influence the radiological progression of rheumatoid arthritis ?, Clinical Rheumatology, 10.1007/BF02114394, 9, 3, (342-345), (1990).
  • , Methotrexate therapy in rheumatoid arthritis. A two year prospective follow-up, Clinical Rheumatology, 10.1007/BF02114393, 9, 3, (333-341), (1990).
  • , Inhibition of in vitro vascular endothelial cell proliferation and in vivo neovascularization by low‐dose methotrexate, Arthritis & Rheumatism, 32, 9, (1065-1073), (2005).
  • , Electron microscopic analysis of sequential liver biopsy samples from patients with rheumatoid arthritis. Correlation with light microscopic findings, Arthritis & Rheumatism, 32, 10, (1202-1213), (2005).
  • , Methotrexate in rheumatoid arthritis: Studies with animal models, Advances in Enzyme Regulation, 29, (247), (1989).
  • , Treatment of rheumatoid arthritis, Arthritis & Rheumatism, 2, 3, (A23-A32), (2005).
  • , Correspondence, American Journal of Kidney Diseases, 14, 1, (76), (1989).
  • , Toxicity and serum levels of methotrexate in children with juvenile rheumatoid arthritis, Arthritis & Rheumatism, 32, 6, (677-681), (2005).
  • , Liver histology in rheumatoid arthritis patients receiving long‐term methotrexate therapy. A Prospective Study with Baseline and Sequential Biopsy Samples, Arthritis & Rheumatism, 32, 2, (121-127), (2005).
  • , METHOTREXATE‐ITS CURRENT USE IN RHEUMATOID ARTHRITIS, Journal of Clinical Pharmacy and Therapeutics, 14, 4, (239-242), (2008).
  • , Radiologic assessment as an outcome measure in rheumatoid arthritis, Arthritis & Rheumatism, 32, 2, (221-229), (2005).
  • , Central nervous system toxicity associated with weekly low‐dose methotrexate treatment, Arthritis & Rheumatism, 32, 6, (770-775), (2005).
  • , Pharmacokinetics of low‐dose methotrexate in rheumatoid arthritis patients, Journal of Pharmaceutical Sciences, 78, 2, (165-171), (2006).
  • , Low-dose methotrexate treatment of rheumatoid arthritis; Long-term observation of efficacy and safety, Clinical Rheumatology, 10.1007/BF02030344, 8, 3, (323-330), (1989).
  • , Eruption of nodulosis and vasculitis during methotrexate therapy for rheumatoid arthritis, Clinical Rheumatology, 10.1007/BF02030360, 8, 3, (417-419), (1989).
  • , Rheumatoid Arthritis, Mayo Clinic Proceedings, 63, 8, (837), (1988).
  • , METHOTREXATE IN RHEUMATOID ARTHRITIS, Australian and New Zealand Journal of Medicine, 18, 7, (831-832), (2008).
  • , PANCYTOPENIA INDUCED BY LOW-DOSE METHOTREXATE FOR RHEUMATOID ARTHRITIS, Australian and New Zealand Journal of Medicine, 18, 5, (697), (1988).
  • , The effects of leucovorin (folinic acid) on methotrexate therapy in rheumatoid arthritis patients, Arthritis & Rheumatism, 31, 7, (906-908), (2005).
  • , METHOTREXATE AND RHEUMATOID ARTHRITIS, Journal of Clinical Pharmacy and Therapeutics, 13, 2, (85-89), (2008).
  • , Methotrexate in rheumatoid arthritis, Arthritis & Rheumatism, 31, 3, (305-314), (2005).
  • , Histopathologic findings in the liver of rheumatoid arthritis patients treated with long‐term bolus methotrexate, Arthritis & Rheumatism, 31, 12, (1457-1464), (2005).
  • , Long‐term prospective trial of low‐dose methotrexate in rheumatoid arthritis, Arthritis & Rheumatism, 31, 2, (167-175), (2005).
  • , Accelerated nodulosis and vasculitis during methotrexate therapy for rheumatoid arthritis, Arthritis & Rheumatism, 31, 9, (1182-1185), (2005).
  • , Methotrexate in psoriasis: Revised guidelines, Journal of the American Academy of Dermatology, 19, 1, (145), (1988).
  • , Hepatotoxicity of Methotrexate in Rheumatic Diseases, Medical Toxicology, 3, 3, (197), (1988).
  • , Methotrexate in rheumatoid arthritis, Journal of the American Academy of Dermatology, 19, 1, (126), (1988).
  • , A long‐term prospective study of the use of methotrexate in rheumatoid arthritis, Arthritis & Rheumatism, 31, 5, (577-584), (2005).
  • , Methotrexate-associated hepatotoxicity: retrospective analysis of 210 patients with rheumatoid arthritis, The American Journal of Medicine, 85, 6, (771), (1988).
  • , 7 Diarrhoea and constipation, Baillière's Clinical Gastroenterology, 2, 2, (353), (1988).
  • , Methotrexate in rheumatoid arthritis: a prospective study in Israeli patients with immunogenetic correlations., Annals of the Rheumatic Diseases, 10.1136/ard.47.8.654, 47, 8, (654-659), (1988).
  • , Folate status of rheumatoid arthritis patients receiving long‐term, low‐dose methotrexate therapy, Arthritis & Rheumatism, 30, 12, (1348-1356), (2005).
  • , Increase of dihydrofolate reductase in peripheral blood lymphocytes of rheumatoid arthritis patients treated with low-dose oral methotrexate, Arthritis & Rheumatism, 30, 4, (369), (1987).
  • , Severe flare of rheumatoid arthritis after discontinuation of long-term methotrexate therapy, The American Journal of Medicine, 82, 4, (781), (1987).
  • , Low dose pulse methotrexate in rheumatoid arthritis: an 8-year experience with hepatotoxicity, Clinical Rheumatology, 6, 4, (575), (1987).
  • , Methotrexate metabolism analysis in blood and liver of rheumatoid arthritis patients: Association with hepatic folate deficiency and formation of polyglutamates, Arthritis & Rheumatism, 29, 7, (832-835), (2005).
  • , Safety of non-steroidal anti-inflammatory drugs and/or paracetamol in people receiving methotrexate for inflammatory arthritis, Cochrane Database of Systematic Reviews, 10.1002/14651858.CD008872, (2010).
  • , Safety of non-steroidal anti-inflammatory drugs, including aspirin and paracetamol (acetaminophen) in people receiving methotrexate for inflammatory arthritis (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, other spondyloarthritis), Cochrane Database of Systematic Reviews, 10.1002/14651858.CD008872.pub2, (2011).
  • , Pharmacogenomics of Methotrexate Membrane Transport Pathway: Can Clinical Response to Methotrexate in Rheumatoid Arthritis Be Predicted?, International Journal of Molecular Sciences, 10.3390/ijms160613760, 16, 6, (13760-13780), (2015).
  • , Role of Single-Agent Methotrexate as a Neoadjuvant Chemotherapy in Oral Cavity Cancers, Indian Journal of Surgical Oncology, 10.1007/s13193-018-0846-3, (2018).