Recommendations for optimizing methotrexate treatment for patients with rheumatoid arthritis

Figures & data

Table 1 Patient characteristics that contraindicate prescription of MTX⁵

Women who are pregnant or breastfeeding

Heavy alcohol users

Patients with

• Alcohol-induced or other chronic liver diseases

• Immunodeficiency

• Renal insufficiency

• Anemia, leukopenia, or thrombocytopenia

• Hypersensitivity to MTX

• Lung disease (eg, pneumonitis or interstitial lung disease of unknown cause)

• Active bacterial or herpes zoster infection, active tuberculosis, or life-threatening fungal infection

Note: © Copyright CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 2004. Reproduced from Rau R, Herborn G. Benefit and risk of methotrexate treatment in rheumatoid arthritis. Clin Exp Rheumatol. 2004;22(5 Suppl 35):S83–S94.⁵

Abbreviation: MTX, methotrexate.

Table 2 MTX dosing in 7 studies included in a meta-analysis of efficacy

No of patients	MTX dose	Duration
12	20–25 mg/wk	27 weeks
33	10 mg/m^2/wk	18 weeks
132	7.5–15 mg/wk	12 weeks
28	15 mg/wk	12 weeks
482	7.5–15 mg/wk	52 weeks
35	15 mg/wk	12 weeks
189	7.5–15 mg/wk	18 weeks

Note: Data from Lopez-Olivo et al.²⁷

Abbreviation: MTX, methotrexate.

Figure 1 Results from the TEMPO trial at 3 years of follow-up: probability plots of changes in total Sharp scores.

Note: Republished with permission of John Wiley and Sons Inc from van der Heijde D, Klareskog L, Landewé R, et al. Disease remission and sustained halting of radiographic progression with combination etanercept and methotrexate in patients with rheumatoid arthritis. Arthritis Rheum. 2007;56(12):3928–3939. © 2007, American College of Rheumatology permission conveyed through Copyright Clearance Center, Inc.³¹

Figure 2 Percentages of patients who achieved a response according to ACR20/50/70 criteria after 2 years of treatment in the TEAR trial.

Notes: Patients received immediate combination therapy, initial MTX therapy with transition to combination therapy, or MTX monotherapy. There were no statistically significant differences among groups. Republished with permission of John Wiley and Sons Inc., from O’Dell JR, Curtis JR, Mikuls TR, et al. Validation of the methotrexate-first strategy in patients with early, poor-prognosis rheumatoid arthritis: results from a two-year randomized, double-blind trial. Arthritis Rheum. 2013;65(8):1985–1994.© 2013, American College of Rheumatology, permission conveyed through Copyright Clearance Center, Inc.³³
Abbreviation: ACR, American College of Rheumatology; MTX, methotrexate.

Figure 3 Results of a retrospective analysis of 103 patients with RA.

Notes: Significant improvement in disease control was observed following transition from oral to subcutaneous MTX (40 patients were switched because of inadequate efficacy; 63 were switched because of gastrointestinal side effects). Republished with permission of John Wiley and Sons Inc., from Hameed B, Jones H. Subcutaneous methotrexate is well tolerated and superior to oral methotrexate in the treatment of rheumatoid arthritis. Int J Rheum Dis. 2010;13(4):e83–e84.© 2010 Asia Pacific League of Associations for Rheumatology and Blackwell Publishing Asia Pty Ltd, permission conveyed through Copyright Clearance Center, Inc.⁵⁶
Abbreviations: RA, rheumatoid arthritis; MTX, methotrexate; DAS28, Disease Activity Score for 28 Joints.

Figure 4 Results from a single-center, open-label, randomized, 2-period, 2-sequence, single-dose, crossover study in 4 dose groups (7.5, 15, 22.5, and 30 mg) with 54 healthy adults treated with oral and subcutaneous MTX.

Note: © 2014 Clinical and Experimental Rheumatology. Reproduced from Pichlmeier U, Heuer KU. Subcutaneous administration of methotrexate with a prefilled autoinjector pen results in a higher relative bioavailability compared with oral administration of methotrexate. Clin Exp Rheumatol. 2014;32(4):563–571.⁵⁹
Abbreviations: MTX, methotrexate; SC, subcutaneous; AUC, area under the curve.

Figure 5 Percentage of patients achieving (A) DAS28 remission and (B) DAS28 low disease activity at baseline and at 6, 12, and 24 months.

Note: DAS28 remission was defined as DAS28 <2.6; low disease activity was defined as DAS28 >2.6 and <3.2. Reproduced from Gallo G, Brock F, Kerkmann U, Kola B, Huizinga TW. Efficacy of etanercept in combination with methotrexate in moderate-to-severe rheumatoid arthritis is not dependent on methotrexate dosage. RMD Open. 2016;2(1):e000186. Copyright © 2016 with permission from BMJ Publishing Group Ltd.¹⁰⁷
Abbreviations: DAS28, Disease Activity Score for 28 Joints; ETN, etanercept; MTX, methotrexate.

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