Combination Therapy for RA Introduces Treatment Variety and Potential Confusion

Biologics are changing how clinicians make treatment choices.

Treatment options for rheumatoid arthritis (RA) have undergone an explosion in choice over the past 25 years and researchers recently analyzed a new combination therapy.

RA treatment evolved from symptomatic relief to implementation of therapeutic regimens that impact disease activity and ultimately have been shown to slow or arrest structural joint damage. Pharmacologic therapy has gone from salicylates, to non-steroidal anti-inflammatory drugs, to disease-modifying anti-rheumatic agents. Through it all, methotrexate (MTX) has remained the stalwart, and MTX monotherapy is still satisfying for many patients with RA.

However, biologics, including anti-TNF inhibitors, are re-defining how clinicians make treatment choices. Studies have consistently shown that MTX in combination with TNF-α inhibitor therapy leads to better outcomes than with either agent alone. The current state of RA therapy is such that it’s no longer a given that patients will move from symptom onset to significant disability.

A recent research report in Arthritis Care & Research illustrated this point by way of a study looking at the effectiveness of the anti-TNF certolizumab pegol (CZP) in combination with MTX. The review looked at MTX with CZP 200 mg, CZP 400 mg or placebo, every two weeks. Inclusion criteria required methotrexate dose ≥10 mg/week. The study measured responses by logistic regression and van der Heijde modified Total Sharp Score (mTSS) analyzed by ANCOVA. Incidence rates of treatment-emergent adverse events (TEAEs) were categorized by baseline MTX dose.

Medication combinations, of course, introduce potentially confusing variety. How much of one medication, combined with how much of the other? This is an important question for not only efficacy but safety as well, and it is often solved by trial and error in clinical testing.

The review looked at 638, 635, and 325 patients who received CZP 200 mg, CZP 400 mg, and placebo, respectively. At week 24, treatment responses in both CZP groups were uninfluenced by baseline methotrexate dose category, and were superior to placebo group, for all investigated endpoints. TEAE incidence rates were higher in patients receiving methotrexate ≥15 mg/week for most TEAE types, across treatment groups.

The researchers found that CZP efficacy was not affected by background methotrexate dose category.

“It can be hypothesized that to minimize TEAEs, background methotrexate doses could be tailored to individual patient tolerance without affecting CZP efficacy,” the study authors concluded.