Methotrexate Dosing Re-Examined with Certolizumab Pegol

Researchers have found that the anti-TNF therapy certolizumab pegol (CZP) reduces the signs and symptoms of rheumatoid arthritis and it protects joints at the same pace regardless of how much methotrexate was prescribed at baseline, which is good news for patients who have difficulty tolerating methotrexate.

Methotrexate is generally administered once weekly at dosages ranging from 7.5 to 30 mg/week. Even though it has one of the best benefit to risk ratios, some rheumatoid arthritis patients cannot tolerate methotrexate and some patients fail to respond completely. In those cases, the dose is increased or combined with other DMARDs which increases the risk of adverse events. When combined with an anti-TNF (tumor necrosis factor) therapy, methotrexate is almost always more effective than it is alone.   [[{"type":"media","view_mode":"media_crop","fid":"46233","attributes":{"alt":"(©LiWa/Shutterstock.com)","class":"media-image media-image-right","id":"media_crop_36233270075","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"5356","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":"(©LiWa/Shutterstock.com)","typeof":"foaf:Image"}}]]

French researchers led by Bernard Combe, M.D., Ph.D., examined the efficacy, safety and tolerability of certolizumab pegol (CZP) in rheumatoid arthritis patients receiving different doses of methotrexate.

The study, which appears in the Feb. 23 online issue of Arthritis Care and Research, is based on data pooled from the phase III clinical trials Rheumatoid Arthritis Prevention of Structural Dam-age 1 (RAPID 1) and RAPID 2 in which patients were assigned to one of three groups:  638 patients received CZP 200 mg; 635 received CZP 400 mg and 325 patients were assigned a placebo.

Combe and his colleagues found that at week 24, the methotrexate dose at baseline did not affect the response to treatment by patients in either certolizumab pegol group, which suggests that patients could theoretically be prescribed less methotrexate. The combined treatment regimen was associated with higher rates of treatment emergent adverse events (TEAEs), primarily of the gastrointestinal tract, but most were mild to moderate.

Methotrexate with Certolizumab Pegol (CZP)

MTX ≤ 10 mg/week

MTX > 10 and ≤ 15 mg/week

MTX > 15 mg/week

CZP 200 mg

ACR20 = 59.9

ACR50 = 30.9

ACR70 = 16.0

CZP 200 mg

ACR20 = 58.3

ACR50 = 40.7

ACR70 = 21.6

CZP 200 mg

ACR20 = 53.6

ACR50 = 39.1

ACR70 = 24.5

MTX ≤ 10 mg/week

MTX > 10 and ≤ 15 mg/week

MTX > 15 mg/week

CZP 400 mg

ACR20 = 59.2

ACR50 = 34.9

ACR70 = 13.2

CZP 400 mg

ACR20 = 63.6

ACR50 = 42.7

ACR70 = 21.4

CZP 400 mg

ACR20 = 52.3

ACR50 = 33.0

ACR70 = 17.4

“This finding should be interpreted with caution, however, as methotrexate dose was not randomly assigned in the present study, and patients on higher methotrexate doses may be more prone to specific TEAEs due to more active disease,” the authors wrote.

Previous studies have evaluated the safety and efficacy of methotrexate as monotherapy or in combination with other DMARDs, but none have examined different methotrexate dosing against the safety and efficacy of anti-TNF therapies.

Similar studies have been conducted usinginfliximab and golimumab. In the Japanese infliximab study, researchers reported a comparable safety and efficacy of infliximab in rheumatoid arthritis patient subgroups receiving concomitant methotrexate at low (≤4 mg/week) or high (≥6 mg/week) doses over 54 weeks. Similar findings were reported for golimumab over a six month period when combined with methotrexate (<10 mg/week, ≥10 and <15 mg/week, or ≥15 mg/week).

Disclosures:

This study was sponsored by UCB Pharma.

References:

 Bernard Combe, Daniel E. Furst, et. al.

"Certolizumab Pegol Efficacy Across MethotrexateRegimens: A Pre-Specified Analysis of TwoPhase III Trials,"

Arthritis Care and Research. Published online Feb. 23, 2016. Vol. 68, No. 3, March 2016, pp 299–307DOI 10.1002/acr.22676