RA ℞: Methotrexate

No difference in efficacy for MTX as monotherapy vs. combination therapy with other csDMARDs for RA

In a systematic literature review informing the 2016…

There are several trials that test the efficacy and safety of combination tumor necrosis factor inhibitor (TNFi) plus methotrexate against triple therapy (methotrexate plus hydroxychloroquine plus sulfasalazine) in patients with rheumatoid arthritis (RA).

A network meta-analysis of the various trials comparing outcomes between “triple therapy” (combination of conventional synthetic DMARDs) and “MTX + targeted DMARD” came to the following conclusions:
1) where clinical response is concerned, the MTX + tDMARD combination yielded deeper response (ACR70);
2) with regards to joint erosions, again the MTX + tDMARD combination was superior, but the rate of progression was not clinically relevant (less than 5 points/year on a scale of 448).

So, start with MTX alone, which is effective enough for most. If response is inadequate, and cost is a concern, you’re not losing anything much by going with combination csDMARDs. Reserve the combination with tDMARD for more severe disease.

Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying antirheumatic drugs for rheumatoid arthritis: abridged Cochrane systematic review and network meta-analysis

Objective  To compare methotrexate based disease modifying antirheumatic drug (DMARD) treatments for rheumatoid arthritis in patients naive to or with an inadequate response to methotrexate. Design  Systematic review and Bayesian random effects network meta-analysis of trials assessing methotrexate…

Objectives Combining disease-modifying antirheumatic drugs (DMARDs) with glucocorticoids (GCs) is an effective treatment strategy for early rheumatoid arthritis (ERA), yet the ideal schedule and feasibility in daily practice are debated. We evaluated different DMARD combinations and GC remission ind…

The key feature of the original COBRA trial is the initial pairing of high dose corticosteroid with combination conventional synthetic DMARDs (csDMARDs eg Methotrexate, Sulfasalazine, Hydroxychloroquine) to achieve rapid control of RA inflammation.

This sequel trial explored various combinations of MTX with other csDMARDs and different doses of Prednisolone, and came to the conclusion that the is no response difference between the groups. As such, pairing MTX as the only csDMARD with the lower steroid dose is the safest and most cost-effective option.

Methotrexate in combination with other DMARDs is not superior to methotrexate alone for remission induction with moderate-to-high-dose glucocorticoid bridging in early rheumatoid arthritis after 16 weeks of treatment: the CareRA trial

Objectives To compare the efficacy and safety of intensive combination strategies with glucocorticoids (GCs) in the first 16 weeks (W) of early rheumatoid arthritis (eRA) treatment, focusing on high-risk patients, in the Care in early RA trial. Methods 400 disease-modifying antirheumatic drugs (DMAR…

Even after TNFi cessation, remission was 34% higher

The case for front-loading targeted therapies: paying forward so you don’t have to pay back. It may have to do with exploiting the initial “window of therapeutic opportunity”.

The February 2017 RheumNow “Live Vote” surveyed US and non-US rheumatologists about their beliefs and practices regarding folic acid and methotrexate (MTX) use. A total of 495 responses were tabulated in 2 weeks. In the first week the survey only went to US rheumatologists from the RheumNow database…

More eminence-based than evidence-based advice, I surmise.

More trials showed folate improving gastrointestinal tolerability to MTX compared to one showing no benefit.
Evidence showed MTX survival superior in folate users than those not on folate.
There is a theoretical cardiovascular protection role for folate, by antagonising MTX-induced hyperhomocysteinemia in some patients.

But, a post-hoc analysis suggested that folate blunts MTX efficacy.
But, most RA patients on MTX do not experience gastrointestinal or mucosal side-effects, or develop liver enzymes elevation.

And, there is absolutely no science involved in the dosing regimen for folate: what dose, weekly or daily, why day-after MTX if weekly, etc.

So, why not NOT ROUTINELY prescribing folate with MTX, unless liver enzymes go up or patients experience nausea? I would entirely stop MTX if mucositis develops.

Does Folic Acid Reduce the Toxicity of Methotrexate?

When used to treat rheumatoid arthritis, low-dose…

Key clinical point: Among patients with recently diagnosed, moderate to severe rheumatoid arthritis,…

Subcutaneous MTX: the poor man’s “biologic”.

Study: Triple conventional therapy was more durable than MTX-etanercept for RA

For patients with rheumatoid arthritis and a suboptimal response to methotrexate, triple conventional…