Combination of certolizumab with methotrexate in rheumatoid arthritis: does methotrexate dose matter?

The authors analyzed the safety and effectiveness of certolizumab pegol (Cimzia) in combination with methotrexate (Trexall) in the treatment of rheumatoid arthritis (RA). 

In RA, high levels of immune system proteins are generated. This causes inflammation, leading to chronic pain. Disease-modifying antirheumatic drugs (DMARDs) are safe and effective treatments used in patients with RA. DMARDs decrease pain and inflammation, reduce or prevent joint damage and preserve the structure and function of the joints. Methotrexate is one of the most commonly used DMARDs in RA treatment. However, some patients cannot tolerate this drug and many do not respond to methotrexate completely. Combining methotrexate with another DMARD has become an effective treatment option in RA. Certolizumab, a biological DMARD, has been shown to decrease RA signs and symptoms when used in combination with methotrexate.

The effectiveness of treatment can be measured using standard scoring systems. These can include the ACR 20/50/70, DAS28 and mTSS scoring systems. The ACR20/50/70 (American College of Rheumatology) response measures 20%, 50% or 70% improvements in swollen or tender joints after treatment. The DAS28 (Disease Activity Score) is an assessment to measure the progress and improvement of RA by examining 28 joints. The mTSS (Modified Total Sharp Score) measures the degree of erosion and narrowing of space between the bones due to cartilage breakdown. 

It is important to understand if the effectiveness of certolizumab is affected by methotrexate dose when used as a combination treatment.

The authors aimed to assess the safety and effectiveness of certolizumab combined with different doses of methotrexate.

There were 3 groups of patients in this phase III clinical trial. 638 patients in group 1 received 200 mg of certolizumab every two weeks. 635 patients in group 2 received 400 mg of certolizumab every two weeks. 325 patients in group 3 received a placebo (control group). Patients in all three groups received additional doses of methotrexate. The dose of methotrexate was either less than 15 mg per week or more than 15 mg per week.

At week 24, all ACR20/50/70 scores were superior in group 1 and group 2 compared to group 3 regardless of methotrexate dose.

The treatment-related side effects were mostly mild to moderate and increased when the methotrexate dose was increased. The most common side effects were urinary tract infections, upper respiratory tract infections and infections in the throat and nasal passages. The occurrence of side effects were greater in patients receiving more than 15 mg of methotrexate per week compared to those receiving less than 15 mg per week. The most serious side effects reported were pneumonia, tuberculosis and erysipelas (large raised red patches on the skin). 

The authors concluded that the effectiveness of certolizumab was not influenced by methotrexate dose. They further suggested that certolizumab could benefit RA patients who were intolerant to high doses of methotrexate. 

RA patients with similar disease grades received different doses of methotrexate. This was possibly due to the differences in local practice of medicines in different countries. It was not known whether the assigned methotrexate dose was appropriate for the patients to control their disease.