JYVÄSKYLÄ, Finland—Treating rheumatoid arthritis (RA) with a combination of disease modifying antirheumatic drugs (DMARDs) plus prednisolone results in sustained remission and blocks the progression of radiographic joint damage in a "remarkable proportion" of patients, according to new results from the Finnish Rheumatoid Arthritis Combination Therapy trial (FIN-RACo). The study appears online in the Journal of Rheumatology.¹

In the study, patients were randomized to receive either a combination of DMARDS (n = 97) or a single DMARD ( n = 98). The researchers defined remission using the modified American College of Rheumatology (ACR) remission criteria (without fatigue) and Disease Activity Score 28 joint count (DAS28) <2.6. They defined sustained remission as the presence of remission at 6, 12, and 24 months. Good treatment response was defined as DAS28 <e;3.2 and decrease of DAS28 >1.2.

Remission as target in both arms

In the combination group, the initial DMARD was sulfasalazine (SSZ) 500 mg twice daily, methotrexate (MTX) at 7.5 mg/week, and hydroxychloroquine (HCQ) at 300 mg/day. Prednisolone 5 mg/day was given with the DMARDs. Doses were adjusted if patients did not achieve at least 50% improvement in two of three prespecified criteria. The criteria included number of swollen joints, number of tender joints, and erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP).

Patients in the single DMARD arm were started on 2 g/day of SSZ. The dose could be increased to 3 g/day. Up to 10 mg/day of prednisolone was permitted but not mandated. SSZ could be replaced by MTX or another single DMARD due to adverse events or lack of efficacy. Discretionary steroid injections were allowed on this arm. Thus, while all patients in the combination DMARD arm received prednisolone, only 61% of patients in the monotherapy arm received it.

In 169 RA patients for whom complete data were available, 14% of patients who received a combination of DMARDs plus prednisolone and 3% who received a single DMARD with or without prednisolone had remissions according to modified ACR criteria (fatigue excluded) at 2 years. (P = .013). The odds ratio for sustained ACR remission was 4.61 favoring combination DMARD/prednisolone therapy.

Sustained remission protects against radiographic joint damage

At 2 years, 50% of patients in the combination group and 16% in the monotherapy group achieved DAS28 remission (P <.001, odds ratio 5.58). As might be expected, over 2 years, the Larsen score of radiographic progression was significantly better in those patients who had sustained remissions.

"Patients in sustained remission had less radiographic progression over 2 years compared to patients who were in remission at 6 months and lost it later; and…sustainability of remission and good treatment response was better in patients who were treated with a combination of DMARDs and low-dose prednisolone compared with monotherapy, with or without prednisolone, although treatment was targeted to remission in both groups," conclude researchers led by Heidi Mäkinen, MD, a rheumatologist at the Jyväskylä Central Hospital in Finland.

The researchers speculate that a greater number of participants in the combination arm may have achieved sustained remission in part due to the mandatory use of prednisolone. However, eight of the 14 patients in the monotherapy arm who achieved sustained remission (DAS28) had not taken prednisolone.

The new findings add "more evidence that earlier and more aggressive treatment is definitely where the field is going, and we can quibble about the details," said Rex McCallum, MD, clinical professor of medicine and associate medical director of the Private Diagnostic Clinic at Duke University Medical Center, in Durham, North Carolina.

Is remission a cure?

"I don't think we can call remission a cure because we don't know what causes RA, so conceptually we can't say we cure it. However, you might be one of those people whose RA stays inactive on therapy or who gets inactive on therapy and stays inactive after discontinuing therapy," Dr. McCallum said. "The trend is toward earlier and more aggressive treatment, and I fully support that we should start with one agent and add something to it if it's not doing everything you want it to."  Dr. McCallum told CIAOMed that he tends to start early RA patients on MTX and to add a biologic if response is inadequate after 4 months.


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Reference

1. Mäkinen H, Kautiainen H, Hannonen P, et al. Sustained remission and reduced radiographic progression with combination disease modifying anti-rheumatic drugs in early rheumatoid arthritis. J Rheumatol. 2006 Dec 15; [Epub ahead of print].