TNFα inhibitors represent a class of biological agents that have gained significant attention for their rapid onset of action and disease modifying properties. Studies show that etanercept, a recombinant TNFα receptor fusion protein, is equivalent to methotrexate (MTX) in RA.7
Infliximab, a chimeric monoclonal IgG1 antibody against TNFα is normally used in combination with MTX for those with an insufficient response to MTX alone.1
A third TNFα inhibitor adalimumab, a human monoclonal antibody, is now available for the treatment of RA.8
Little information is available about the clinical benefit of changing from one TNFα inhibitor to another when the first agent has demonstrated a lack of efficacy or caused adverse events.
A French study described the usefulness of switching TNFα inhibitors among 131 patients with RA receiving either etanercept or infliximab.9
Eight patients switched from infliximab to etanercept, with five reporting improvement in RA symptoms, while six switched from etanercept to infliximab with clinical improvement in three. A retrospective study reported that patients with RA who do not respond to etanercept might experience improved disease control with a switch to infliximab. The efficacy of infliximab was clinically and statistically similar in subjects who had never received anti‐TNFα treatment. Indeed, disease activity improved significantly in both groups.10
In a recent study, 25 patients who discontinued infliximab were subsequently treated with etanercept in a prospective, open label, 12 week study. It was shown that etanercept was well tolerated and effective in treating patients with RA, even when infliximab was stopped.11
Another study from Stockholm showed that for patients with insufficient efficacy from etanercept, treatment with infliximab provided better results, suggesting that a trial of infliximab is reasonable in such patients. On the other hand, for patients who discontinued infliximab owing to adverse events, treatment with etanercept gave at least a similar clinical efficacy.12
Thus, in these two clinical situations: when etanercept fails owing to a lack of efficacy, and when infliximab fails owing to adverse events, trying the alternative of these two TNFα blockers does make clinical sense.13
Our study adds to the existing data by comparing the response of patients with RA who switch from infliximab to adalimumab, with that of patients receiving adalimumab with no previous TNFα treatment. After 12 months' adalimumab treatment, the degree of clinical response was similar in both groups. In addition, no significant difference was found in the safety profile of both groups. No specific side effects due to infliximab treatment are predictors for adverse events or response to treatment by switching to adalimumab. As far as we know, no previous studies have described the efficacy of adalimumab in patients with RA who previously discontinued infliximab treatment. However, there are some pilot and case report studies in patients with Crohn's disease who discontinued infliximab and were treated with adalimumab. They showed that adalimumab was well tolerated and appears to be a clinically beneficial option for patients with Crohn's disease who have lost their response to, or cannot tolerate, infliximab.14,15,16
The results of this study reinforce the above and provide strong evidence that adalimumab is a well tolerated and effective treatment option for patients with RA, even when infliximab has been discontinued. It is interesting to note that treatment with adalimumab in our study was started for some patients 4 weeks after the last infliximab infusion. There may have been a carry over effect of infliximab. This may strengthen the conclusion of our study, because patients who switched to adalimumab tolerated the treatment well.
A weakness of this study is the small number of patients in each group, which might result in a lower power, or ability to detect differences in the efficacy of adalimumab between groups. Thus, research is needed with larger numbers of patients to determine which patients' characteristics predict a response to different TNFα inhibitors, such as pharmacokinetics, TNFα polymorphisms, and cytokine profile.