Systematic review of 2008-2012 literature and update of recommendations for the use of methotrexate in rheumatic diseases, with a focus on rheumatoid arthritis

Todoerti, Monica; Maglione, Wanda; Bernero, E.; Bortoluzzi, Alessandra; Colaci, Michele; Galuppi, E.; Paolino, Sabrina; Talarico, Rosaria; Cutolo, Maurizio; Ferri, Clodoveo; Trotta, Francesco; Bombardieri, Stefano; Montecucco, Carlomaurizio; Sinigaglia, Luigi

doi:10.4081/reumatismo.2013.207

Cited by 15 publications

(25 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Bioavailability data discussed herein are reflected in the latest Italian recommendations and guidelines on the management of RA [ 7 , 22 ]. While guidelines permit a broad therapeutic range (7.5–25.0 mg/week), the optimal treatment strategy requires initial doses higher than those recommended in the past (12.5–15.0 mg/week).…”

Section: Discussionmentioning

confidence: 99%

Methotrexate and Rheumatoid Arthritis: Current Evidence Regarding Subcutaneous Versus Oral Routes of Administration

et al. 2016

View full text Add to dashboard Cite

Methotrexate (MTX) is still considered the drug of choice in rheumatoid arthritis (RA) management. Comparing subcutaneous (MTX SC) and oral (MTX OR) routes of administration is important to optimize the everyday therapeutic strategy in the real-life setting. This review summarizes scientific evidence currently available on this topic. As shown by pharmacokinetic studies, at the same dose level, bioavailability of MTX SC is significantly higher and less variable than that of MTX OR. This difference is even more pronounced for medium-to-high dosages (i.e., >15 mg/week). With regard to clinical response (Disease Activity Score-28, American College of Rheumatology Criteria), randomized, double-blind studies and retrospective or longitudinal analyses in real-life settings showed that MTX SC is more effective than MTX OR. This is true both in MTX-naive patients with early RA, and in patients who switch from MTX OR to MTX SC due to previous treatment failure, lack of efficacy and/or adverse events. Finally, MTX SC has a better tolerability profile than MTX OR, with fewer gastroenterological side effects. Delaying the use of more expensive biological therapies by switching from MTX OR to MTX SC in non-responders might provide cost savings, with relevant implications in the management of patients with RA.FundingAlfa Wassermann.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-016-0295-8) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Methotrexate and Rheumatoid Arthritis: Current Evidence Regarding Subcutaneous Versus Oral Routes of Administration

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Current guidelines recommend initially treating early RA (ie, <6 months) and established RA with DMARDs 2–4. Although MTX is the initial drug of choice for most patients with RA, this medication is contraindicated for some individuals (Table 1).…”

Section: Introductionmentioning

confidence: 99%

Recommendations for optimizing methotrexate treatment for patients with rheumatoid arthritis

Bello

Perkins²,

Jay

et al. 2017

OARRR

View full text Add to dashboard Cite

Methotrexate (MTX) remains the cornerstone therapy for patients with rheumatoid arthritis (RA), with well-established safety and efficacy profiles and support in international guidelines. Clinical and radiologic results indicate benefits of MTX monotherapy and combination with other agents, yet patients may not receive optimal dosing, duration, or route of administration to maximize their response to this drug. This review highlights best practices for MTX use in RA patients. First, to improve the response to oral MTX, a high initial dose should be administered followed by rapid titration. Importantly, this approach does not appear to compromise safety or tolerability for patients. Treatment with oral MTX, with appropriate dose titration, then should be continued for at least 6 months (as long as the patient experiences some response to treatment within 3 months) to achieve an accurate assessment of treatment efficacy. If oral MTX treatment fails due to intolerability or inadequate response, the patient may be “rescued” by switching to subcutaneous delivery of MTX. Consideration should also be given to starting with subcutaneous MTX given its favorable bioavailability and pharmacodynamic profile over oral delivery. Either initiation of subcutaneous MTX therapy or switching from oral to subcutaneous administration improves persistence with treatment. Upon transition from oral to subcutaneous delivery, MTX dosage should be maintained, rather than increased, and titration should be performed as needed. Similarly, if another RA treatment is necessary to control the disease, the MTX dosage and route of administration should be maintained, with titration as needed.

show abstract

“…Therefore, in RA patients refractory to oral MTX, switching to parenteral administration has been recommended as a useful strategy before introducing other therapies. 57 , 58 …”

Section: Discussionmentioning

confidence: 99%

Update on subcutaneous methotrexate for inflammatory arthritis and psoriasis

Veña¹,

Cassano²,

Iannone³

2018

TCRM

View full text Add to dashboard Cite

Methotrexate (MTX) is one of the mainstays of treatment for several immune-mediated inflammatory joint and skin diseases, especially rheumatoid arthritis (RA) and moderate-to-severe psoriasis. Oral MTX has been used for the treatment of such diseases for decades for many reasons. There is, however, a relevant interpatient variability of clinical and safety outcomes that can also be related to differences in patients’ individual pharmacogenomic profile. Orally administered MTX has been found to have a saturable intestinal absorption and nonlinear pharmacokinetics, with significant consequences on drug bioavailability and clinical efficacy. The current evidence shows that parenterally administered MTX results in rapid and complete absorption, higher serum levels, and less variable exposure than oral dosing. The use of parenteral MTX, particularly when administered as a subcutaneous (SC) injection, has recently raised great interest in order to overcome the limitations of oral MTX. The effectiveness and safety of SC MTX have mostly been assessed in rheumatological settings, especially in patients with RA. There are only a limited number of data on SC MTX in juvenile idiopathic arthritis and even fewer in psoriatic disease. Various clinical experiences have suggested that SC MTX is more effective than oral MTX and may provide significant benefit even in patients in whom oral MTX proved to be inadequate. The increased efficacy of SC MTX resulting from higher drug exposure compared with oral MTX has been associated with a similar safety profile and in various reports even with a lower frequency of gastrointestinal complaints. The aim of this article was to review the available literature data on SC MTX treatment of inflammatory arthritis, with special emphasis on RA and psoriasis, examining differences with oral MTX treatment. A brief mention of pharmacokinetics, pharmacodynamic features and pharmacoeconomic considerations is also given.

show abstract

Systematic review of 2008-2012 literature and update of recommendations for the use of methotrexate in rheumatic diseases, with a focus on rheumatoid arthritis

Cited by 15 publications

References 57 publications

Methotrexate and Rheumatoid Arthritis: Current Evidence Regarding Subcutaneous Versus Oral Routes of Administration

Methotrexate and Rheumatoid Arthritis: Current Evidence Regarding Subcutaneous Versus Oral Routes of Administration

Recommendations for optimizing methotrexate treatment for patients with rheumatoid arthritis

Update on subcutaneous methotrexate for inflammatory arthritis and psoriasis

Contact Info

Product

Resources

About