Long‐Term Prospective Study of Methotrexate in the Treatment of Rheumatoid Arthritis

Weinblatt, Michael E.; Weissman, Barbara N.; Holdsworth, Donald; Fraser, Patricia A.; Maier, Agnes L.; Falchuk, Kenneth R.; Coblyn, Jonathan S.

doi:10.1002/art.1780350202

Cited by 217 publications

(90 citation statements)

References 20 publications

(14 reference statements)

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“…These studies and those by Weinblatt and colleagues (7,8) have demonstrated that MTX can be continued over periods of as long as 7.5 years while maintaining improvement in the clinical features and functional status compared with baseline. This is noteworthy because enrollees in these investigations, which were begun in 1982, had active RA and, by definition, had failed therapy with several other disease-mo-g antirheumatic drugs (DMARDs).…”

Section: Safety Efficacy and Mortality In A Long-term Cohort Of Patmentioning

confidence: 78%

“…This is noteworthy because enrollees in these investigations, which were begun in 1982, had active RA and, by definition, had failed therapy with several other disease-mo-g antirheumatic drugs (DMARDs). Weinblatt has recently reported that clinical improvement was sustained in his cohort over a period of 11 years, but no mortality or functional status data were reported (9).…”

Section: Safety Efficacy and Mortality In A Long-term Cohort Of Patmentioning

confidence: 95%

“…Pincus (1) and Wolfe et a1 (2) have both shown that "most patients with RA experience a progressive disease over long periods, with early radiographic damage, functional declines, work disability, and premature mortality rates" (1). It is also stated that "apparent improvement over intermediate periods of [5][6][7][8][9][10] years" may be seen in traditional outcome measures, such as the number of tender joints, even while patients experience "substantial declines in functional status" during these same periods (1,3).…”

Section: Safety Efficacy and Mortality In A Long-term Cohort Of Patmentioning

confidence: 99%

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Safty, efficacy, and mortality in a long‐term cohort of patients with rheumatoid arthritis taking methotrexate: Folloup after a mean of 13.3 years

Kremer

1997

Arthritis & Rheumatism

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Section: Safety Efficacy and Mortality In A Long-term Cohort Of Patmentioning

confidence: 78%

Section: Safety Efficacy and Mortality In A Long-term Cohort Of Patmentioning

confidence: 95%

Section: Safety Efficacy and Mortality In A Long-term Cohort Of Patmentioning

confidence: 99%

See 1 more Smart Citation

Safty, efficacy, and mortality in a long‐term cohort of patients with rheumatoid arthritis taking methotrexate: Folloup after a mean of 13.3 years

Kremer

1997

Arthritis & Rheumatism

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“…hFRβ expression is increased in certain leukemias, most consistently seen in chronic myelogenous leukemia and acute myelogenous leukemia (43,45). hFRβ expression is also increased in activated synovial macrophages, cells involved in the pathogenesis of rheumatoid arthritis and other inflammatory conditions including psoriasis and Crohn's disease (37,39,46,47).…”

mentioning

confidence: 99%

Structures of human folate receptors reveal biological trafficking states and diversity in folate and antifolate recognition

Wibowo

Singh

Reeder

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

176

190

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Antifolates, folate analogs that inhibit vitamin B 9 (folic acid)-using cellular enzymes, have been used over several decades for the treatment of cancer and inflammatory diseases. Cellular uptake of the antifolates in clinical use occurs primarily via widely expressed facilitative membrane transporters. More recently, human folate receptors (FRs), high affinity receptors that transport folate via endocytosis, have been proposed as targets for the specific delivery of new classes of antifolates or folate conjugates to tumors or sites of inflammation. The development of specific, FR-targeted antifolates would be accelerated if additional biophysical data, particularly structural models of the receptors, were available. Here we describe six distinct crystallographic models that provide insight into biological trafficking of FRs and distinct binding modes of folate and antifolates to these receptors. From comparison of the structures, we delineate discrete structural conformations representative of key stages in the endocytic trafficking of FRs and propose models for pH-dependent conformational changes. Additionally, we describe the molecular details of human FR in complex with three clinically prevalent antifolates, pemetrexed (also Alimta), aminopterin, and methotrexate. On the whole, our data form the basis for rapid design and implementation of unique, FR-targeted, folate-based drugs for the treatment of cancer and inflammatory diseases.isothermal titration calorimetry | targeted drug delivery

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“…Compared with other, more traditional disease-modifying antirheumatic drugs (DMARDs), methotrexate has a more rapid onset of action, superior long-term effectiveness, and fewer cumulative toxicities (3)(4)(5)(6). Studies show that 80% of patients discontinue other DMARDs after 2 years, while at least 50% continue to take methotrexate for Ͼ5 years (7)(8)(9).…”

mentioning

confidence: 99%

Etanercept added to background methotrexate therapy in patients with rheumatoid arthritis: Continued observations

Kremer¹,

Weinblatt²,

Bankhurst³

et al. 2003

Arthritis & Rheumatism

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Objective. To observe the long-term safety and efficacy of combination therapy with etanercept and methotrexate in patients with rheumatoid arthritis (RA), and to determine whether the addition of etanercept allowed reductions in methotrexate or corticosteroid dosages while maintaining a clinical response.Methods. Patients with RA who received methotrexate plus etanercept in a previous randomized, placebo-controlled trial were offered the opportunity to enroll in an open-label extension study for further evaluation of treatment with etanercept and methotrexate.Results. Seventy-nine of the 89 patients in the original blinded study enrolled in the extension study, and 65 of these patients continue in the study. Patients have received etanercept therapy for up to 47 months (median 44 months). The types and rate of adverse events noted during the extension trial were similar to those observed in the controlled trial. At the 3-year assessment, 77% of the 57 patients available for evaluation met American College of Rheumatology 20% (ACR20) criteria for improvement in RA, 47% met the ACR50 criteria, and 23% met the ACR70 criteria. Of the 36 patients assessed at 3 years in the extension study, 30 (83%) were able to decrease their dosages of corticosteroids, and 20 (56%) were able to discontinue corticosteroid therapy. At 3 years, the dosage of methotrexate was decreased in 41 of 66 patients (62%), and methotrexate therapy was discontinued in 19 patients (29%).Conclusion. In this observational continuation study, the addition of etanercept to background methotrexate provided sustained clinical benefit over a median period of 44 months. With etanercept therapy, there were trends toward dosage reduction or discontinuation of methotrexate and corticosteroids, without apparent worsening of ACR response rates. Compared with the controlled trial, no increases in the rate of adverse events were observed.Over the past several decades, methotrexate has become increasingly recognized among rheumatologists as the gold standard in treating patients with rheumatoid arthritis (RA) (1,2). Compared with other, more traditional disease-modifying antirheumatic drugs (DMARDs), methotrexate has a more rapid onset of action, superior long-term effectiveness, and fewer cumulative toxicities (3-6). Studies show that 80% of patients discontinue other DMARDs after 2 years, while at least 50% continue to take methotrexate for Ͼ5 years (7-9). However, despite its advantages over traditional agents, methotrexate is associated with toxicity, and Supported by Immunex Corporation, Seattle, Washington (study drug and grants to the investigational sites).

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Long‐Term Prospective Study of Methotrexate in the Treatment of Rheumatoid Arthritis

Cited by 217 publications

References 20 publications

Safty, efficacy, and mortality in a long‐term cohort of patients with rheumatoid arthritis taking methotrexate: Folloup after a mean of 13.3 years

Safty, efficacy, and mortality in a long‐term cohort of patients with rheumatoid arthritis taking methotrexate: Folloup after a mean of 13.3 years

Structures of human folate receptors reveal biological trafficking states and diversity in folate and antifolate recognition

Etanercept added to background methotrexate therapy in patients with rheumatoid arthritis: Continued observations

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