Monotherapy for rheumatoid arthritis treatment?

Sirs, I read with interest the paper (1) and the accompanying editorial (2) published in the Lancet regarding the ADACTA trial. However, there are issues with this editorial, which seems to reach conclusions not justified by the data from the trial. Monotherapy in RA may be a possibility for some patients (3) but which agent or agents should be preferred has not been studied in comparative studies adequately enough to be able to make firm recommendations. ADACTA trial was designed as a double blind randomised trial which enrolled rheumatoid arthritis patient who had had an inadequate response to methotrexate (MTX). Patients were randomised to monotherapy tocilizumab or adalimumab. The primary outcome was change in DAS28 score at 24 weeks from baseline; it was significantly better for tocilizumab than adalimumab (1). The author of the editorial (2) suggests that “Previous studies indicate that tocilizumab monotherapy is significantly better than MTX monotherapy, whereas adalimumab therapy is not significantly better than MTX therapy” and gives two references, none of which is a tocilizumab vs. MTX monotherapy trial. If the author meant the AMBITION (4) trial which was reference 2 of the editorial, it was not a well carried out study to reach this conclusion as at least 1/3 of the patients had been on MTX before the trial and were re-randomised to MTX, hence it could not be used to determine if tocilizumab monotherapy would have been better than MTX monotherapy. There are currently no published studies that compare MTX monotherapy vs. tocilizumab monotherapy in MTX naive RA patients to see if there are any differences. In addition, the author concludes at the end of his editorial that “...when a biological DMARD monotherapy is the only choice, tocilizumab is the best option available...”. What is this based on? Maybe if the sentence was limited to “ if the only options are tocilizumab or adalimumab then tocilizumab is the better option” it would have been more acceptable, even though it can be argued that the patients in the ADACTA trial are far from the typical patients seen in routine care with tender and swollen joint counts in the double digits. Furthermore, where are the data to suggest tocilizumab is better than any other biologic, let alone another TNF inhibitor used as monotherapy? As the title of a recent editorial states, I would also suggest “Nullius in verba”. We must stick to conclusions based only on solid data (5).