Underestimation of the efficacy, effectiveness, tolerability, and safety of weekly low-dose methotrexate in information presented to physicians and patients.
Ten specific examples of the underestimation of the efficacy, effectiveness and tolerability, and overestimation of adverse events of weekly, low-dose methotrexate, administered with folic acid, in treatment of rheumatic diseases are summarised. These examples include: 1) meta-analyses of clinical trials suggest that methotrexate has an efficacy similar to other disease-modifying anti-rheumatic drugs (DMARDs); 2) information in textbooks and websites may overstate adverse events and drug interactions associated with weekly low-dose methotrexate; 3) information presented to patients when filling a prescription for methotrexate understates 'side effects' of RA and overstates those of methotrexate; 4) an admonition to patients to refrain entirely from consumption of alcohol while taking methotrexate may be unnecessary; 5) frequent blood testing in patients who take methotrexate may be overused; 6) eligibility of only a small minority of patients for clinical trials to compare biologic agents and methotrexate; 7) Step-up design in most comparisons of biologic agents with methotrexate includes only patients who had experienced an incomplete response to methotrexate; 8) in parallel design trials, the efficacy of biologic agents is not substantially greater than that of methotrexate; 9) low, inflexible dosage schedules of methotrexate and requirement for withdrawal with minimal liver function abnormalities in many clinical trials may underestimate efficacy, effectiveness, tolerability and safety; 10) interpretation of clinical trial results may overstate the clinical significance of lower radiographic progression in patients treated with biologic agents versus patients treated with methotrexate. More accurate interpretation of information for physicians and other health professionals, as well as patients, concerning use of weekly low-dose methotrexate in contemporary care could improve care and outcomes for patients with RA and other rheumatic diseases.
Department of Medicine, Division of Rheumatology, New York University School of Medicine and NYU Hospital for Joint Diseases, New York, NY 10003, USA. tedpincus@gmail.com
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D000428:Alcohol Drinking / Q000009:adverse effects; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001688:Biological Products / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003257:Consumer Product Safety; D004334:Drug Administration Schedule; D004347:Drug Interactions; D016903:Drug Monitoring; D019317:Evidence-Based Medicine; D005492:Folic Acid / Q000627:therapeutic use; D007722:Health Knowledge, Attitudes, Practice; D006801:Humans; D015201:Meta-Analysis as Topic; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D010353:Patient Education as Topic; D017410:Practice Guidelines as Topic; D012107:Research Design; D012216:Rheumatic Diseases / Q000188:drug therapy*; D018570:Risk Assessment; D013997:Time Factors; D016896:Treatment Outcome; D014803:Vitamin B Complex / Q000627:therapeutic use
D018501:Antirheumatic Agents; D001688:Biological Products; D014803:Vitamin B Complex; D005492:Folic Acid; D008727:Methotrexate