RA Treatment Strategies
Clifton Bingham, M.D. - Jon Giles, M.D.
Abstract 1306: Induction of Remission in Patients with Early Rheumatoid Arthritis (RA) Initially Treated with Either Prednisone or Infliximab Combination Therapy
One exciting but unresolved question in RA management is whether aggressive therapy very early in disease can “turn off” the inflammatory disease processes of RA such that the magnitude and trajectory of the disease is permanently altered. This concept of remission induction is explored here by Van der Kooij et al in results from the BeSt trial (Dutch for “Treatment Strategies”).
Methods The design of the BeSt trial has been described previously on this site (link to EULAR 2004 OP0001). For this analysis, subjects in groups 3 (initial COBRA combination therapy) and 4 (initial combination therapy with methotrexate and infliximab) were compared for the proportions of subjects able to taper down therapy at three years due to sustained low disease activity states based on pre-defined criteria.
Results 133 and 123 subjects were originally enrolled in groups 3 and 4, respectively. Baseline demographic and RA disease characteristics were balanced between the two groups. Mean duration from symptom onset in both groups was 23 weeks with a mean baseline DAS28 of 4.4 in both groups. Approximately 65% of subjects were seropositive for rheumatoid factor at baseline and the median amount of radiographic damage at baseline was 4 Sharp-van der Heijde units. At 3 years, 129 and 120 subjects remained in groups 3 and 4, respectively.
| Characteristics at 3 years |
Group 3 |
Group 4 |
p |
| Responders (sustained DAS<2.4) able to taper DMARDs |
46/129 (36%) |
64/120 (53%) |
0.005 |
| Responders with DAS < 1.6 and no DMARDs |
9/129 (7%) |
17/120 (14%) |
0.064 |
| Proportion remaining on initial combination regimen |
20/129 (16%) |
21/120 (18%) |
ns |
| Proportion not achieving low disease activity |
51/129 (40%) |
31/120 (26%) |
0.022 |
There were no significant differences in radiographic progression between subjects in either group subdivided by response. However, radiographic progression was numerically the lowest in group 4 responders. Adverse and serious adverse events were similar between the two groups.
Conclusions Aggressive initial combination therapy with infliximab + methotrexate with the option for step-down was more effective than initial COBRA combination therapy with the option for step-down in maintaining a sustained clinical response at 3 years.
Editorial Comment One of the unique design elements of the BeSt trial was the incorporation of the ability to discontinue infliximab therapy for sustained clinical response, a strategy that is not widely utilized in clinical practice in the U.S. From these data, initial combination therapy with methotrexate and a TNF inhibitor with the plan for discontinuing the TNF inhibitor when low disease activity is attained appears to be a very effective strategy for ensuring a sustained good clinical response, with most subjects able to discontinue the TNF inhibitor. It remains to be answered whether this strategy is superior to “stepping-up” to the TNF inhibitor, since the BeSt trial did not incorporate such an arm for comparison. Whether these data prove that remission induction is better with initial TNF inhibitor combinations vs. the COBRA combination is another matter. Because the subjects were enrolled very early in disease, some proportion will spontaneously remit within the first year or so of disease. Because the subjects were all treated early, it is difficult to parse out those who would have spontaneously remitted from those who had sustained remission due to their treatment regimen. Larger differences than the 7% vs. 14% presented here might be more convincing, particularly if the subjects who were able to discontinue all DMARDs met some criteria at baseline associated with disease progression (such as a high proportion of RF seropositivity or baseline erosive disease). Short of that, it is a concept very difficult to prove.
