Rheumatoid Arthritis Quiz: How well do you know methotrexate?

September 24, 2019

Valerie DeBenedette is managing editor of Drug Topics.

Methotrexate is the trusted standby in drug regimens to treat rheumatoid arthritis. How much do you know about the current research on methotrexate for rheumatoid arthritis? Take our quiz.

Methotrexate is the trusted standby in drug regimens to treat rheumatoid arthritis. How much do you know about the current research on methotrexate for rheumatoid arthritis? Take our quiz.

Parenteral methotrexate vs oral methotrexate: Methotrexate can be administered either parenterally or orally. Bujor et al. conducted a meta-analysis, published in PLOS One, of randomized studies that enrolled 703 patients with RA with a primary endpoint of ACR20 at six months. The dose of methotrexate in the studies started at 15 mg/week and increased up to 25 mg/week.

The researchers generated an odds ratio for the relative treatment effects. What was the odds ratio for parenteral versus oral methotrexate? 0.8? 1.6? 3.02? 4.5?

Source: Bujor et al.: "Comparison of oral versus parenteral methotrexate in the treatment of rheumatoid arthritis: A meta-analysis."PLoS One. 2019 Sep 6;14(9):e0221823. doi: 10.1371/journal.pone.0221823.

ANSWER: 3.02. An odds ratio higher than 1 means that there is a benefit for using parenteral methotrexate over oral methotrexate. “We propose that parenteral methotrexate is more effective than weekly oral methotrexate; its widespread use may lead to better control of disease and a decrease in demand for biologic agents,” the authors wrote.

Methotrexate intolerance and BMI: Many patients who are prescribed methotrexate discontinue the drug because of intolerance or laboratory abnormalities. To find out if there are clinical or genetic markers that can predict adverse effects with methotrexate, Sandhu and colleagues conducted a prospective study that was published in Clinical Rheumatology. They enrolled 110 patients with RA who were treated with methotrexate. Methotrexate intolerance (symptomatic adverse effects) was common and occurred in 37% patients over 6 months.

They found a modest predictive association between methotrexate intolerance and body mass index (BMI), but was the association with low BMI or high BMI?

Source: Sandhu A, et al. "Clinico-genetic model to predict methotrexate intolerance in rheumatoid arthritis." Clinical Rheumatology. 2019 Sep 14. doi: 10.1007/s10067-019-04770-4.

ANSWER: Low BMI. Methotrexate intolerance was associated with lower BMI at baseline (21.5 ± 3.7, 23.8 ± 4.6 kg/m2, p = 0.01). In BMI calculations, 21 is about the midpoint of what is considered the healthy range.

Methotrexate intolerance and your genes: In the same study, Sandhu et al. genotyped seven single nucleotide polymorphisms (SNPs) in each patient. These SNPs are involved in how the body handles methotrexate.

How many SNPs did they find, that when combined with the patient’s BMI, were modestly predictive of methotrexate intolerance? One? Three? Four? All seven?

Source: Sandhu A, et al. "Clinico-genetic model to predict methotrexate intolerance in rheumatoid arthritis." Clinical Rheumatology. 2019 Sep 14. doi: 10.1007/s10067-019-04770-4.

ANSWER: One. Only SNP FPGS 10101 was found to have a modestly prediction ability for methotrexate intolerance in combination with low BMI.

Oral or subcutaneous? In a similar study published in Advances in Therapy, Bianchi et al. compared subcutaneous and oral methotrexate, evaluating evidence published up until 2015.

Which route of administration was found to provide greater efficacy and tolerability, oral or subcutaneous?

Source: Bianchi G, et al.: "Methotrexate and rheumatoid arthritis: Current evidence regarding subcutaneous versus oral routes of administration." Adv Ther. 2016; 33: 369–378. doi: 10.1007/s12325-016-0295-8

ANSWER: Subcutaneous. Greater efficacy was seen with subcutaneous administration in both patients who had not been treated with methotrexate before and in those who were switched from oral to subcutaneous administration because of treatment failure, lack of efficacy and/or adverse events. Subcutaneous methotrexate also had a better tolerability profile than oral methotrexate. “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,” the authors wrote.

Reduced blood cell count: Vanni, Lyu, and Solomon, writing in Rheumatology (Oxford), conducted a meta-analysis to evaluate the incidence of anemia, leucopenia, neutropenia, and thrombocytopenia in patients with rheumatic diseases who were treated with methotrexate and folic acid.

They found 30 studies with a total of more than 3,800 RA patients. Were cytopenias common or uncommon?

Source: Vanni KMM, Lyu H, Solomon DH: "Cytopenias among patients with rheumatic diseases using methotrexate: a meta-analysis of randomized controlled clinical trials." Rheumatology (Oxford). 2019 Aug 23. pii: kez343. doi: 10.1093/rheumatology/kez343.

ANSWER: Cytopenias were found to be uncommon. The incidence for any anemia was 2.55% (95% CI 0.60-5.47%), any leucopoenia 1.17% (95% CI 0.16-2.80%), any neutropenia 1.77% (95% CI 0.33-4.00%), and any thrombocytopenia 0.19% (95% CI 0.00-0.86%).