Triple Treatment Effective in Early Rheumatoid Arthritis

Pam Harrison

June 11, 2015

ROME — In the early stages of rheumatoid arthritis, combination therapy with conventional disease-modifying antirheumatic drugs (DMARDs) allows a significant proportion of patients to achieve sustained remission as early as 6 months, according to results from a new study.

"Prior to the millennium, we told every rheumatoid arthritis patient that they had to take their medication for the rest of their life," said Angelique Weel, MD, from Erasmus University in Rotterdam, the Netherlands.

"But now we can say to these patients that it is possible to taper their medications. It is even possible to get them drug-free within 2 years if you hit them hard in the first phase of the disease," she told Medscape Medical News.

The study results were presented here at the European League Against Rheumatism (EULAR) Congress 2015.

The Treatment in the Rotterdam Early Arthritis Cohort (tREACH) study involved 281 patients with rheumatoid arthritis.

At baseline, mean disease activity score was 3.2 and median score on the 3-point Health Assessment Questionnaire — which is a good predictor of future disability — was 1.

All patients received methotrexate with glucocorticoid bridging, and the patients randomized to triple DMARD induction also received sulfasalazine and hydroxychloroquine.

Improvements With Triple Therapy

After 3 months of treatment, improvements in the Health Assessment Questionnaire score were significantly greater in the triple-DMARD group than in the methotrexate group (P < .05). This pattern remained significant during the 2-year follow-up period, irrespective of disease activity.

The onset of rheumatoid arthritis typically occurs in people 30 to 50 years of age, when they are in the prime of their working life and have family needs, so functional ability is paramount, Dr Weel explained.

Remission, defined as a disease activity score below 1.6, was achieved earlier in the triple-DMARD group than in the methotrexate group. However, approximately half of both groups had achieved sustained remission 2 years after initiation of treatment.

tREACH was designed as a step-up study, Dr Weel explained. If patients continued to have active disease, defined as a disease activity score above 2.4, they received a biologic, initially in the form of an anti-tumor necrosis factor (TNF) inhibitor.

At 2 years, fewer patients in the triple-DMARD group than in the methotrexate group had received an anti-TNF inhibitor (21% vs 38%).

When a patient achieved a disease activity score below 1.6 on two consecutive visits, rheumatologists could consider tapering the drug regimen, Dr Weel reported.

Tapering was initiated in 80% of the triple-DMARD group and in 90% of the methotrexate group, she added.

As medications were tapered, 43% of patients in each group experienced a flare. Medications were reintroduced in 65% of patients in the triple-DMARD group and in 78% of those in the methotrexate group.

At the end of 2 years, 19% of patients in each group were in drug-free remission, Dr Weel reported.

Joint damage progression was minimal and similar in the two groups.

"There are studies now in which investigators give anti-TNF induction therapy, but when you compare these with our combination of conventional DMARDs given for the first 3 months, the results are absolutely the same," Dr Weel said, "so you really do not have to start with a biologic in the first few months."

"Our data showed an earlier decrease in disease severity and improvements in functional ability in the combination therapy groups, compared with monotherapy," she reported. And there were "significant numbers of patients achieving drug-free remission using a less expensive biologic during the first 2 years of therapy. These data should alleviate concerns regarding the need for long-term aggressive therapy."

Safety Concerns

Concerns about the safety of the triple-DMARD induction regimen were raised by EULAR President Maurizio Cutolo, MD, from the University of Genoa in Italy.

"Safety is an important issue when we consider using triple drug therapy," he said.

"This is why the official EULAR recommendation is to start with monotherapy plus low-dose glucocorticoid bridging, then you can add in another DMARD and, after 6 months, move on to a biologic," he explained.

Dr Weel countered by citing safety findings from a previous study of the triple induction regimen she was involved in (Ann Rheum Dis. 2014;73:1331-1339).

In that study, "patients who started the combination of conventional DMARDs did get more adjustments in therapy than those in the monotherapy arm, but we did not need to stop the medication," she explained. In addition, "there was no difference in discontinuation rates between the two groups."

Dr Weel and Dr Cutolo have disclosed no relevant financial relationships.

European League Against Rheumatism (EULAR) Congress 2015: Abstract OP0030. Presented June 11, 2015.

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