Randomized trials comparing regimens for rheumatoid arthritis find triple therapy is least costly and more effective than other approaches.
de Jong PH, Hazes JM, Han HK, et al., Randomised comparison of initial triple DMARD therapy with methotrexate monotherapy in combination with low-dose glucocorticoid bridging therapy; 1-year data of the tREACH trial. Ann Rheum Dis. (2014) doi:10.1136/annrheumdis-2013-204788 [E-pub may 1, 2014] open access]
Wailoo A, HernÃ¡ndez MA, Scott IC, et al.Cost-effectiveness of treatment strategies using combination disease-modifying anti-rheumatic drugs and glucocorticoids in early rheumatoid arthritis. Rheumatology (Oxford). (2014) Apr 25. [Epub ahead of print]
Methotrexate (MTX) and glucocorticoids (GCs) are mainstays in the treatment of rheumatoid arthritis, along with combinations of various disease modifying antirheumatic drugs (DMARDs). Two newly-published randomized studies affirm the effectiveness – and cost-effectiveness – of these regimens
One study, from the Netherlands, shows that triple DMARD therapy with MTX and a single intramuscular GC injection helped more patients achieve remission after a year than the same therapy using oral GCs.
A second study from Britain finds that giving MTX along with early GCs in triple DMARD therapy was not only clinically effective over two years, but also saved money compared to regimens lacking triple therapy.
Reaching conclusions in tREACH
Data from the first study come from a single-blinded, randomized trial involving 281 patients judged at high risk for progression to persistent arthritis, recruited from the Rotterdam Early Arthritis Cohort (tREACH) and followed for a year.
The tREACH Patients were assigned to one of three treatment arms:
• A) Initial triple therapy of sulfasalazine and hydroxychloroquine, with oral MTX and a single intramuscular injection of either methylprednisolone or triamcinolone(n=91)
• B) The same MTX-sulfasalazine-hydroxychloroquine triple therapy but using oral GCs, tapering slowly over the course of 10 weeks, as “bridging” therapy (n=93)
• C) MTX monotherapy with oral GCs using the same tapering regimen as in group B (n=97)
Patients were seen every 3 months and X-rays of the hands and feet were taken at baseline and every 6 months.
After a year, 61% of the RA patients in treatment arm A, but only about half of patients in groups B and C, reached remission according to American College of Rheumatology (ACR) criteria, having disease activity scores (DAS) below 1.6.
If a patient had a DAS of 2.4 or above (ACR moderate to severe disease activity), treatment was intensified using biologicals. A DAS below 1.6 on two consecutive visits triggered tapering of the triple therapy.
After 3 months, compared to patients given initial methotrexate monotherapy, 40% fewer in the triple therapy groups needed treatment intensification. After a year, 27% of the injection group and 43% of those on oral CGs were using biologicals.
There were no differences in progression of radiographic damage.
Biological use did not differ between the tapered GC bridging therapy groups, nor were there any differences in adverse events (AEs). The researchers concluded that the GC bridging therapies are equally effective.
Cost Savings in CARDERA
The Combination of Anti-Rheumatic Drugs in Early RA (CARDERA) trial from the UK found that triple therapy -- MTX, cyclosporin, and short-term GCs -- was the least costly and most effective over two years, compared to three other regimens.
The CARDERA trial involved 464 patients with active RA of less than two years’ duration, two-thirds of whom were Caucasian women in their 50s, randomized to receive:
• MTX monotherapy (n=117)
• MTX with a stepped-down regimen of prednisolone or a matching placebo (n=119)
• MTX with cyclosporin started after 3 months or a matching placebo (n=115)
• Triple therapy of MTX plus cyclosporin and the stepped-down prednisolone regimen (n=116)
Two-year cost analysis for each treatment strategy showed that primary care costs were negligible across all four groups, drug costs were lowest with MTX/cyclosporin and triple therapy, and the hospital costs were lowest for MTX/prednisolone and triple therapy.
Triple therapy resulted in the lowest Disease Activity in 28 Joints (DAS28) score (mean of 5.61) and achieved the highest benefits in Quality Adjusted Life Years (QALYs).