In arithmetic and newly diagnosed rheumatoid arthritis alike, three is greater than one.
Initial triple disease-modifying therapy with either of two glucocorticoid (GC) bridging therapies proved quicker in attaining treatment goals and required fewer treatment intensifications for patients with very early RA than did initial methotrexate monotherapy with oral GC therapy, according to the results of a randomized, comparative trial.
Several previous clinical trials concluded that initial combination therapy had better clinical efficacy than monotherapy. However, most rheumatologists have not incorporated this into daily practice, according to Dr. Pascal Hendrik Pieter de Jong of the University Medical Center, Rotterdam, the Netherlands, and his colleagues.
Previous combination-therapy studies have usually been disregarded, the researchers noted, because the trials were biased by the use of GCs. So, Dr. de Jong and his colleagues compared the benefits of the 1-year clinical efficacy of initial triple disease-modifying antirheumatic drugs to the benefits of initial methotrexate monotherapy unbiased by the use of GC therapy, either oral or intramuscular.
Primary outcomes of the study were the area under the curve of the Health Assessment Questionnaire (to assess functional ability) and Disease Activity Score (to assess disease state), and the proportion of patients with radiographic progression, the investigators reported online May 1 in Annals of the Rheumatic Diseases (Ann. Rheum. Dis. May 1, 2014 [doi: 10.1136/annrheumdis-2013-204788]).
The study population comprised the 281 patients with a high probability of progress to persistent arthritis (greater than 70%) who were in the Rotterdam Early Arthritis Cohort (tReach) trial. All patients were over age 18, with arthritis in one or more joints and symptom duration of less than 1 year; 68% of the patients were women.
Patients were randomized to one of three arms:
1) initial triple disease-modifying therapy (iTDT) of methotrexate plus sulfasalazine and hydroxychloroquine, with GCs administered intramuscularly,
2) iTDT with an oral GC tapering scheme, or
3) initial methotrexate monotherapy (iMM) with oral GCs similar to the second treatment arm.
Concurrent treatment with nonsteroidal anti-inflammatory drugs and intra-articular injections (maximum of two per 3 months) was allowed.
The largest difference in disease activity states between the treatment arms was seen after 3 months, although that effect gradually diminished to nonsignificance by 12 months. Similarly, there were no significant differences in functional ability at 12 months.
After 3 months, 40% fewer biological agents were prescribed in the iTDT group than in the iMM group, and that difference persisted over time. However, disease activity, functional ability, and radiographic progression were not different between the two treatments after 12 months, regardless of GC bridging therapies. Early initiation of biological agents in the iMM group might have prevented or delayed the radiographic progression, the researchers suggested.
There were no differences in serious adverse events seen in the treatment arms, but the proportion of patients with medication adjustments due to adverse events was significantly higher in the iTDT (65%), compared with the iMM group (45%). No differences were seen between the two GC bridging therapies. Gastrointestinal complaints (56%) and fatigue (36%) were the two most commonly reported adverse events.
"We found no differences in disease activity, functional ability, and radiographic progression after 12 months of treatment owing to our treat-to-target approach (intensifying treatment until the target is reached)," the investigators observed. "Therefore, it is not the endpoint, but progress towards the endpoint, which matters most."
In addition, delaying the implementation of biological agents with iTDT treatment resulted in "reducing costs enormously," according to the researchers, although the cost-utility analysis of the tREACH trial has to reconfirm this, they added.
"We think that future research should focus on developing a more personalized treatment approach, in which differentiation between patients who would thrive on iMM and those who need iTDT might be a first step," they said.
"Before choosing the initial treatment strategy, rheumatologists should be aware of the benefits and the risks, but additionally, known prognostic factors and the patient’s wish should be taken into account. One single intramuscular GC injection and a low-dose, oral GC tapering scheme would be sufficient as bridging therapy," the researchers concluded.
The research was supported by an unrestricted grant from Pfizer, which had no involvement in the study design, data collection, analysis, or publication of the results. Data management was sponsored by the Dutch Arthritis Foundation. The authors reported that they had no competing interests.