Methotrexate—the Relationship Between Dose and Clinical Effect

Seideman, P

doi:10.1093/rheumatology/32.8.751

Cited by 53 publications

(29 citation statements)

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“…At higher doses, the intestinal folate transport system saturates and the parenteral route is required to achieve higher blood levels (19). Although a direct relationship between the MTX dose and clinical response has been well established in RA over the dose range of 7.5-25 mg/week (8,21), the efficacy of dose escalation in patients achieving a partial response to oral MTX has not been formally examined.…”

Section: Discussionmentioning

confidence: 99%

Dose escalation of parenteral methotrexate in active rheumatoid arthritis that has been unresponsive to conventional doses of methotrexate: A randomized, controlled trial

Lambert¹,

Sandhu²,

Lochhead³

et al. 2004

Arthritis & Rheumatism

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Results. Sixty-four patients were eligible for entry and were switched from oral MTX to 15 mg/week IM MTX. At baseline, the mean ؎ SD DAS28 was 5.6 ؎ 0.88; after 6 weeks of IM MTX, the DAS28 had improved by a mean of 0.42 (95% confidence interval [95% CI] 0.15-0.69). At 6 weeks, 54 patients still had a DAS28 of >3.2 and were therefore eligible for randomization. By 22 weeks, 1 patient (3.7%) in each group achieved the primary outcome of a DAS28 <3.2 (95% CI for the difference between the groups ؊15% to ؉15%). Five patients (18.5%) in each group showed an improvement of >1.2 in the DAS28 (95% CI for the difference between the groups ؊18% to ؉18%). One patient (3.7%) in each group achieved an ACR20 response, but none achieved a good response as defined by the EULAR response criteria. One patient in each group had a serious adverse reaction; minor adverse reactions were more frequently reported in the dose escalation group.Conclusion. Switching from oral to parenteral MTX 15 mg/week results in a minor improvement in disease control. For patients with active RA receiving 15

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Section: Discussionmentioning

confidence: 99%

Dose escalation of parenteral methotrexate in active rheumatoid arthritis that has been unresponsive to conventional doses of methotrexate: A randomized, controlled trial

Lambert¹,

Sandhu²,

Lochhead³

et al. 2004

Arthritis & Rheumatism

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“…In patients with RA, both a trend toward a dose-response relationship (16,17) and no association between dose and response have been reported with oral MTX (18). Serum MTX concentrations have been shown to have no correlation with disease activity (19).…”

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confidence: 99%

Pharmacokinetics of oral methotrexate in patients with rheumatoid arthritis

Dalrymple¹,

Stamp²,

O’Donnell³

et al. 2008

Arthritis & Rheumatism

172

136

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Objective. There is evidence supporting a therapeutic range for methotrexate polyglutamate ( Conclusion. There is wide interpatient variability of RBC MTXGlu 1-5 accumulation and elimination in adults with RA. These data also suggest that after a dose change, >6 months are required for RBC MTXGlu 1-5 to reach steady state. Such delays in achieving steady state suggest that more rapid dose escalation or subcutaneous administration from the outset should be considered.

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“…However subject numbers were small and a larger study might reveal the cause of some of this variability. Although a doseresponse relationship has been described for MTX in RA patients [2] it is not currently known how much of the variability in the dose-response relationship is pharmacokinetic in origin. Plot of methotrexate concentrations and Figure 3 Population (-) and posterior (---) fits for subject 1.…”

Section: Discussionmentioning

confidence: 99%

“…Low dose methotrexate (MTX) is now widely used as a second-line treatment for rheumatoid arthritis (RA) [ 11. Clinical effects and side effects have been shown to be dose related and MTX dosage should be individualized [2]. Differences in the pharmacokinetics of MTX between individuals is a potential source of variability in the dose-effect relationship and marked interindividual variability in MTX bioavailability has been noted [3].…”

Section: Introductionmentioning

confidence: 99%

Lack of interaction between flucloxacillin and methotrexate in pa tien t s with rheumatoid arthritis

Herrick

Grennan

Griffen

et al. 1996

Brit J Clinical Pharma

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The aim of the study was to examine the potential pharmacokinetic interaction between methotrexate and flucloxacillin. Ten rheumatoid arthritis patients participated in the interaction study. Subjects were allocated to either methotrexate alone (5-15 mg per week) or methotrexate plus flucloxacillin (500 mg four times a day 48 h prior to sampling) in a random order. There was a statistically, but not clinically, significant decrease in methotrexate AUC (1307 i -389 us 1212 f 394 pg I-' h) in the presence of flucloxacillin. C, , , and t, , , parameters for methotrexate were not significantly altered in the presence of flucloxacillin. Data from an additional 10 rheumatoid arthritis patients, starting on methotrexate, were added to the data from the placebo arm of the interaction study and a model dependent pharmacokinetic analysis was performed. The plasma concentration profiles were best described by a two-compartment model with a mean clearance of 11.9 (& 1.7) 1 h-l and an initial volume of distribution of 31.2 (& 2.6) 1. The pronounced intersubject variability in the pharmacokinetic parameters was not related to any of the available covariate information. Our findings suggest that no important clinical interaction occurs between flucloxacillin and methotrexate in patients with rheumatoid arthritis.

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Methotrexate—the Relationship Between Dose and Clinical Effect

Cited by 53 publications

References 0 publications

Dose escalation of parenteral methotrexate in active rheumatoid arthritis that has been unresponsive to conventional doses of methotrexate: A randomized, controlled trial

Dose escalation of parenteral methotrexate in active rheumatoid arthritis that has been unresponsive to conventional doses of methotrexate: A randomized, controlled trial

Pharmacokinetics of oral methotrexate in patients with rheumatoid arthritis

Lack of interaction between flucloxacillin and methotrexate in pa tien t s with rheumatoid arthritis

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