Adalimumab (Humira) is Safe and Effective When Administered Concomitantly with Standard Anti-Rheumatic Therapy for the Treatment of Rheumatoid Arthritis (RA)
Methods: 636 patients with RA were randomly assigned to receive adalimumab (40 mg subcutaneously every other week) or placebo for 24 weeks. If patients were already receiving treatment with pre-existing DMARDs, low dose prednisone (< 10 mg qd) and nonsteroidal anti-inflammatory drugs (NSAIDs), these drugs were continued. The primary outcome was frequency of adverse events; the secondary outcomes were ACR 20/50/70 responses.
Results: 318 patients received adalimumab and 318 received placebo. 83.5% of all patients enrolled in the study received at least one DMARD in combination with adalimumab. Overall, 56.0% continued treatment with one DMARD, 23.6% with 2 DMARDs, and 3.9% with > 3 DMARDs. At 24 weeks of treatment, there were no significant differences between the adalimumab and placebo groups in the following:
| Events | Adalimumab (%) | Placebo (%) |
| Adverse events | 86.5 | 82.7 |
| Serious adverse events | 5.3 | 6.9 |
| Infections | 52.2 | 49.4 |
| Serious infections | 1.3 | 1.9 |
The incidence and types of adverse events did not vary between the treatment groups as a function of the number of DMARDs they were receiving. Adalimumab-treated patients had superior ACR responses compared to placebo-treated patients, as below:
| Adalimumab (%) | Placebo (%) | |
| ACR20 | 52.8 | 34.9 |
| ACR 50 | 28.9 | 11.3 |
| ACR 70 | 14.8 | 3.5 |
Conclusions: This study attempts to mimic “real life” clinical practice by examining the safety and efficacy of adalimumab in combination with a variety of DMARDs routinely used to treat RA. As such, it is similar in design to a previously reported clinical trial with the IL-1 receptor antagonist, anakinra (Kineret®) (see previous report). It is encouraging to note the low incidence of serious infections and other adverse events in the adalimumab-treated patients despite the fact that some patients were receiving 3 or more DMARDs.
Editorial Comments: In the early clinical trials with adalimumab prior to screening for latent tuberculosis (TB), there was a relatively high incidence of TB. In later clinical trials and in this trial, however, FDA guidelines were followed in that patients had to be pre-screened and treated (if positive) for latent tuberculosis prior to enrollment in the trials. This has resulted in nearly complete elimination of this infectious complication of anti-TNF treatment.
It is also important to note that patients receiving anakinra (Kineret®) were excluded from participation in this study; this is because the combination of another TNF inhibitor (etanercept) with anakinra has been associated with a high incidence of infection (see prior study).
The ACR responses to adalimumab in this trial were statistically significantly better than, but relatively modest compared to, placebo. The placebo rates, especially the ACR20s, were high in this study, perhaps because a significant percentage of the patients enrolled were on more than one DMARD. Nonetheless, adalimumab provided superior efficacy compared to placebo alone.
