Pulmonary disease during the treatment of rheumatoid arthritis with low dose pulse methotrexate

doi:10.1016/0049-0172(87)90021-7

Seminars in Arthritis and Rheumatism

Volume 16, Issue 3, February 1987, Pages 186-195

https://doi.org/10.1016/0049-0172(87)90021-7 Get rights and content

Abstract

Methotrexate therapy has been effective in the treatment of RA with short term experience suggesting little serious adverse reactions. Our review of 168 patients receiving methotrexate has identified nine patients with probable or possible methotrexate-induced pulmonary toxicity, giving a prevalence of 5% and an incidence of 3.9 per 100 patients per year. No clinical or laboratory features showed an association that could potentially predict the development of pulmonary disease. All patients experienced complete recovery with supportive care and/or corticosteroid therapy. Clinical monitoring for this complication is warranted in all patients receiving long term methotrexate therapy for RA.

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Cited by (169)

Methotrexate use reduces mortality risk in rheumatoid arthritis: A systematic review and meta-analysis of cohort studies
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Rheumatoid arthritis(RA) sufferers have a higher mortality risk than the healthy population, and methotrexate (MTX) as a base drug for RA treatment is believed to affect patients mortality. Systematic analyses of MTX and RA mortality are lacking and it is still confused about the role of MTX on the long-term prognosis of RA.
We performed a systematic review and meta-analysis to identify any influence of MTX on mortality among RA patients. Hazard ratio(HR) for all-cause mortality were pooled in a meta-analysis, and HR for mortality from RA with cardiovascular diseases (RA-CVD) and mortality from RA associated interstitial lung diseases (RA-ILD) were also pooled and analyzed.
Fifteen studies were eventually included. Meta-analysis of data from 15 studies on overall mortality showed that MTX significantly reduced mortality in patients with RA (HR = 0.59, 95%CI 0.50–0.71, P < 0.001), MTX was independently associated with decreased RA-CVD-induced mortality (HR = 0.72, 95%CI 0.53–0.97, P = 0.031). In the meanwhile, MTX was also significantly reduced mortality in RA-ILD (HR = 0.44, 95%CI 0.20–0.95, P = 0.037).
MTX can significantly decrease the overall mortality for RA patients, specifically, RA-CVD- and RA-ILD-induced mortality were reduced.
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Citation Excerpt :
Because of the prevalence of hepatotoxicity, the American College of Rheumatology published guidelines for monitoring MTX-induced hepatic toxicity in RA patients [184,185]. Around 25% RA patients who applied MTX therapy were reported to show wheezing, coughing, exertional dyspnea or other pulmonary symptoms [29,122,139,186–190]. Patients might experience pulmonary side effects as early as four weeks after initiation of treatment which are suggested to be an idiosyncratic immune reaction instead of a dose-related toxic insult to the lung [128,191–193].
Methotrexate (MTX) is used as an anchor disease-modifying anti-rheumatic drugs (DMARDs) in treating rheumatoid arthritis (RA) because of its potent efficacy and tolerability. MTX benefits a large number of RA patients but partially suffered from side effects. A variety of side effects can be associated with MTX when treating RA patients, from mild to severe or discontinuation of the treatment. In this report, we reviewed the possible side effects that MTX might cause from the most common gastrointestinal toxicity effects to less frequent malignant diseases. In order to achieve regimen with less side effects, the administration of MTX with appropriate dose and a careful pretreatment inspection is necessary. Further investigations are required when combining MTX with other drugs so as to enhance the efficacy and reduce side effects at the same time. The management of MTX treatment is also discussed to provide strategies for occurred side effects. Thus, this review will provide scholars with a comprehensive understanding the side effects of MTX administration by RA patients.
Chemotherapy Agents With Known Pulmonary Side Effects and Their Anesthetic and Critical Care Implications
2017, Journal of Cardiothoracic and Vascular Anesthesia
Traditional DMARDs: Methotrexate, Leflunomide, Sulfasalazine, Hydroxychloroquine, and Combination Therapies
2016, Kelley and Firestein's Textbook of Rheumatology: Volumes 1-2, Tenth Edition
Interstitial lung diseases induced or exacerbated by DMARDS and biologic agents in rheumatoid arthritis: A systematic literature review
2014, Seminars in Arthritis and Rheumatism
To review published cases of induced or exacerbated interstitial lung disease (ILD) in rheumatoid arthritis (RA) associated with non-biologic disease-modifying antirheumatic drugs (nbDMARDs) and biologics and to discuss clinical implications in daily practice.
We performed a systematic literature review from 1975 to July 2013 using Medline, Embase, Cochrane, and abstracts from the ACR 2010–2012 and EULAR 2010–2013 annual meetings. Case reports and series that suggest a causative role of nbDMARDs (methotrexate [MTX], leflunomide [LEF], gold, azathioprine [AZA], sulfasalazine [SSZ], and hydroxychloroquine [HCQ]) and biologic agents (TNF inhibitors [TNFi], rituximab [RTX], tocilizumab [TCZ], abatacept [ABA], and anakinra) in causing ILD or worsening a pre-existing ILD in RA patients were included. Results from observational and postmarketing studies as well as reviews on this topic were excluded from the qualitative analysis but still considered to discuss the implication of such drugs in generating or worsening ILD in RA patients. Comparisons were made between MTX-induced ILD in RA and the cases reported with other agents, in terms of clinical presentation, radiological features, and therapeutic management and outcomes.
The literature search identified 32 articles for MTX, 12 for LEF (resulting in 34 case reports), 3 for gold, 1 for AZA, 4 for SSZ, 27 for TNFi (resulting in 31 case reports), 3 for RTX, 5 for TCZ (resulting in 8 case reports), and 1 for ABA. No case was found for HCQ or anakinra. Common points are noted between LEF- and TNFi-related ILD in RA: ILD is a rare severe adverse event, mostly occurs within the first 20 weeks after initiation of therapy, causes dyspnea mostly in older patients, and can be fatal. Although no definitive causative relationship can be drawn from case reports and observational studies, these data argue for a pulmonary follow-up in RA patients with pre-existing ILD, while receiving biologic therapy or nbDMARDs.
As previously described for MTX, growing evidence highlights that LEF, TNFi, RTX, and TCZ may induce pneumonitis or worsen RA-related pre-existing ILD. Nonetheless, identifying a causal relationship between RA therapy and ILD-induced toxicity clearly appears difficult, partly because it is a rare condition.

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^☆: Supported by a Clinical Research Center grant from the Arthritis Foundation and a grant from Lederle Laboratories.

¹: From the Division of Rheumatology, Department of Internal Medicine and Department of Family and Community Medicine, University of Utah School of Medicine and Veterans Administration Medical Center, Salt Lake City.

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Pulmonary disease during the treatment of rheumatoid arthritis with low dose pulse methotrexate☆

Abstract

Am J Med

Am J Med

J Urol

Am J Med

Comparison of low-dose oral pulse methotrexate and placebo in the treatment of rheumatoid arthritis

Arthritis Rheum

Efficacy of low-dose methotrexate in rheumatoid arthritis

N Engl J Med

Weekly pulse methotrexate in rheumatoid arthritis. Clinical and immunologic effects in a randomized, double-blind study

Ann Intern Med

Low dose pulse methotrexate therapy in rheumatoid arthritis

J Rheumatol

Weekly intravenous methotrexate in the treatment of rheumatoid arthritis

Arthritis Rheum

Acute and chronic effects of methotrexate on hepatic, pulmonary, and skeletal systems

Cancer

Pulmonary and hepatic complications of methotrexate therapy of psoriasis

JAMA

Methotrexate-induced pneumonitis

Medicine

Cooperative Study

Pulmonary disease complicating intermittent therapy with methotrexate

JAMA

Methotrexate pneumonitis induced by intrathecal methotrexate therapy. A case report with pharmacokinetic data

Cancer

Methotrexate-induced sudden fatal pulmonary reaction

Cancer

Methotrexate therapy and pulmonary disease

Radiology

Progressive interstitial lung disease from prolonged methotrexate therapy

Arch Dermatol

Methotrexate-induced diffuse interstitial pulmonary fibrosis

South Med J

Severe pneumonitis occurring during methotrexate therapy

Arch Dermatol

Methotrexate therapy in polymyositis

Ann Rheum Dis

Acute lung disease associated with low-dose pulse methotrexate therapy in patients with rheumatoid arthritis

Arthritis Rheum

Methotrexate pneumonitis after low-dose therapy for rheumatoid arthritis

Arthritis Rheum