Does Methotrexate Increase the Risk of Infection or Malignancy?

Kanik, Keith S.; Cash, Joseph M.

doi:10.1016/s0889-857x(05)70368-9

Cited by 62 publications

(30 citation statements)

References 65 publications

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“…Iikuni et al also showed that the use of MTX for patients with connective tissue disease is related to susceptibility to PCP [41]. A search of literature from Western countries revealed that P. jiroveci is the most common opportunistic infection in RA patients treated with low-dose MTX [5,6,42]. As mentioned above, the PMS report on infliximab by JCR indicated a high incidence of PCP in RA patients treated with infliximab (22 cases of PCP out of 5,000 patients) [13].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, patients taking MTX seem to be at risk of opportunistic infections, such as cytomegalovirus pneumonia, disseminated herpes zoster infection, cryptococcosis, widespread nocardiosis, and Pneumocystis jiroveci pneumonia (PCP) [5,6]. However, the exact role of MTX in inducing infections is unclear since patients with RA have a predisposition to pulmonary infections [7], and MTX is sometimes used concomitantly with corticosteroids, a major predisposing factor for PCP development in RA patients [8].…”

Section: Introductionmentioning

confidence: 99%

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Asymptomatic carriage of Pneumocystis jiroveci in elderly patients with rheumatoid arthritis in Japan: a possible association between colonization and development of Pneumocystis jiroveci pneumonia during low-dose MTX therapy

et al. 2008

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Low-dose methotrexate (MTX) has been used effectively for rheumatoid arthritis (RA) because of its favorable risk-benefit ratio. One of the recent concerns arising from this therapy is a possible increase in the rate of opportunistic infections, particularly Pneumocystis jiroveci pneumonia (PCP). In this study, we report two cases of PCP occurring during low-dose methotrexate therapy for RA and review 13 additional cases from the literature on Japanese patients with RA. The average age of these patients was 67.7 years, and most were over the age of 60. MTX-associated PCP appears to occur more frequently in elderly individuals in Japan. To identify individuals with a high risk of PCP, we performed a polymerase chain reaction on specimens from induced sputum or bronchoalveolar lavage fluids from 55 patients with RA. At that point in time, they showed no evidence of PCP development. We found six patients (10.9%) having asymptomatic carriage of P. jiroveci. The mean age of the P. jiroveci-positive patients was 74.7 years, which was significantly older than the P. jiroveci-negative patients (mean age 63.6 years). Of the RA patients over the age of 65, 18.8% (6 cases out of 32) were carriers of P. jiroveci. There were no significant differences in RA duration or counts of white blood cells or lymphocytes between the positive and negative groups. Notably, we encountered a case of PCP occurring in an asymptomatic carrier of P. jiroveci during low-dose MTX therapy for RA. This case appeared to be a reactivation of latent infection. By careful follow-up on the carriers of P. jiroveci, we succeeded in promptly diagnosing PCP, and we employed the appropriate therapeutic strategies for this possibly life-threatening complication.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Asymptomatic carriage of Pneumocystis jiroveci in elderly patients with rheumatoid arthritis in Japan: a possible association between colonization and development of Pneumocystis jiroveci pneumonia during low-dose MTX therapy

et al. 2008

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“…There are case reports of severe colitis complicating the use of methotrexate, although not yet in patients with Crohn's disease 9. There is an increased risk of opportunistic infections, including herpes zoster and pneumocystis carinii pneumonia, but not of neoplasia other than lymphoproliferative disorders 10. The latter are related to previous infection with Epstein-Barr virus, and are sometimes reversible on methotrexate withdrawal.…”

Section: Side Effectsmentioning

confidence: 99%

Methotrexate in Crohn's disease

Rampton

2001

Gut

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“…Disease activity and measures of severity have been associated with higher risk of infection [9], even before the biologics era [4]. Furthermore, common immunosuppresive treatments [3,10–14] have also been associated with infection [15–17]. Therefore, it is unclear whether the observed risk of infection in RA is a product of disease-related activity, pharmacologically-induced immunosuppression, common co-morbid conditions, or a combination of these factors.…”

Section: Introductionmentioning

confidence: 99%

TNF-<i>α</i> Antagonist and Infection in Rheumatoid Arthritis

Mittleman¹,

Shadick²,

Karlson³

2012

OJRA

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Background Anti-TNF treatment may increase infection risk, although this has been difficult to study because the timing of anti-TNF treatment is driven by disease activity, which may influence infection susceptibility leading to confounding that varies over time. We evaluated the association between anti-TNF initiation in rheumatoid arthritis (RA) patients on disease modifying anti-rheumatic drugs (DMARD) and infection using multiple approaches adjusting for time-varying confounding. Methods 383 anti-TNF-naïve RA patients on ≥1 non-biologic-DMARD at enrollment from the Brigham and Women's Rheumatoid Arthritis Sequential Study (BRASS) were followed up to two years. Pooled logistic regressions estimated the association between anti-TNF and infection by including time-varying covariates in the adjusted models and inverse probability treatment weighting (IPTW). Results Adjustment for time-varying disease activity and other suspected confounders yielded non-statistically significant positive associations between anti-TNF start and infection regardless of analytic approach (RRmvar_adj = 2.1, 95% CI: 0.8 – 5.8). Conclusions Incorporating changing clinical status, and treatment indications and consequences, yielded consistently (though not significantly) elevated relative risks of infection associated with anti-TNF initiation. Due to limited statistical power, we cannot draw firm conclusions. However, we have illustrated multiple approaches adjusting for potential time-varying confounding in longitudinal studies and hope to replicate the approaches in larger studies.

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Does Methotrexate Increase the Risk of Infection or Malignancy?

Cited by 62 publications

References 65 publications

Asymptomatic carriage of Pneumocystis jiroveci in elderly patients with rheumatoid arthritis in Japan: a possible association between colonization and development of Pneumocystis jiroveci pneumonia during low-dose MTX therapy

Asymptomatic carriage of Pneumocystis jiroveci in elderly patients with rheumatoid arthritis in Japan: a possible association between colonization and development of Pneumocystis jiroveci pneumonia during low-dose MTX therapy

Methotrexate in Crohn's disease

TNF-<i>α</i> Antagonist and Infection in Rheumatoid Arthritis

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Does Methotrexate Increase the Risk of Infection or Malignancy?

Cited by 62 publications

References 65 publications

Asymptomatic carriage of Pneumocystis jiroveci in elderly patients with rheumatoid arthritis in Japan: a possible association between colonization and development of Pneumocystis jiroveci pneumonia during low-dose MTX therapy

Asymptomatic carriage of Pneumocystis jiroveci in elderly patients with rheumatoid arthritis in Japan: a possible association between colonization and development of Pneumocystis jiroveci pneumonia during low-dose MTX therapy

Methotrexate in Crohn's disease

TNF-&lt;i&gt;α&lt;/i&gt; Antagonist and Infection in Rheumatoid Arthritis

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TNF-<i>α</i> Antagonist and Infection in Rheumatoid Arthritis