GLASGOW, Scotland—Triple therapy with conventional disease-modifying antirheumatic drugs (DMARDs) is equally effective when initiated on an intensive step-up schedule or as effective when all three drugs are started at once, and response rates in early active rheumatoid arthritis (RA) are as high as those seen with biologics, according to new research in Arthritis & Rheumatism.1

"This study confirms that highly effective control of disease activity can be achieved using conventional DMARDs as part of an intensive disease management strategy. Within this setting, step-up therapy is at least as effective as parallel triple therapy."—Sarah Saunders, MB ChB, MRCP
"This study confirms that highly effective control of disease activity can be achieved using conventional DMARDs as part of an intensive disease management strategy. Within this setting, step-up therapy is at least as effective as parallel triple therapy," conclude researchers led by Sarah Saunders, MB ChB, MRCP, at the centre for rheumatic diseases of the Glasgow Royal Infirmary in Scotland.

Step-up versus triple therapy

The Tight Control of RA (TICORA) study previously demonstrated that an intensive step-up DMARD treatment strategy targeting persistent disease activity was superior to routine care in the management of early RA. The researchers set out to determine whether early parallel triple therapy could produce even better outcomes than step-up therapy within an intensive disease management regimen.

The cohort comprised 96 patients with early RA (mean disease duration 11.5 months). Patients were randomized to receive step-up therapy (sulfasalazine [SSZ] monotherapy, then after 3 months, methotrexate [MTX] was added, and when the maximum tolerated dosage of MTX was reached, hydroxychloroquine [HCQ] was added) or parallel triple therapy (SSZ/MTX/HCQ).

All patients were assessed monthly for 12 months. If disease activity score 28 (DAS28) joints was ≥3.2, the dosage of DMARDs was increased according to protocol and swollen joints were injected with triamcinolone acetonide at a maximum dosage of 80 mg/month.

Both groups showed substantial improvements in disease activity and functional outcome. The mean decrease in DAS28 score was -4.0 (step-up therapy group) versus -3.3 (parallel therapy group) at 1 year. There were also no significant differences in the percentages of patients with DAS28 remission (step-up therapy group 45% vs parallel triple therapy group 33%), DAS28 response (60% vs 41%, respectively), ACR20 (77% vs 76%, respectively), ACR50 (60% vs 51%, respectively), or ACR70 (30% vs 20%, respectively). X-ray progression was similar in both groups, the study showed.

Newer is not necessarily better, although it is more expensive

Tumor necrosis factor-alpha (TNF-α) blockers could have been added if patients has failed to respond or did not tolerate maximum doses of triple therapy, but no patients in the 12-month study received a TNF-blocker.

"Despite the use of conventional DMARDs, clinical response rates seen in our patients were similar to those reported in trials of etanercept, infliximab, and adalimumab in early RA," the researchers wrote.

Translating research into practice

Not everyone is convinced that triple therapy with conventional DMARDs is the best approach in early RA. "I don't think that it is a good strategy, and I also do not believe that many rheumatologists practice this strategy," Désirée van der Heijde MD, PhD, professor of rheumatology at the University Hospital of Maastricht, in The Netherlands, told MSKreport.com. "Most rheumatologists start with high dose of MTX."

Reference
1. Saunders SA, Capell HA, Stirling A, et al. Triple therapy in early active rheumatoid arthritis. A randomized, single-blind, trial comparing step-up and parallel treatment strategies. Arthritis Rheum. 2008;58:1310-1317.