The authors endeavor to refute possible misgivings about basic antirheumatic therapies (1). However, the cited literature is presented incorrectly in part.
For the statement that glucocorticoids can be discontinued or at least reduced to the lowest possible dose for the majority of patients with rheumatoid arthritis (RA), the authors cite the SEMIRA study (2). In this study, patients who were already on tocilizumab (68) or had been newly started on tocilizumab (191) and who presented with stable, low disease activity while taking 5 mg/day of prednisone were randomized into two groups: continued drug intake versus tapering off the glucocorticoids. The two groups were followed up for eight weeks after the end of the 16-week tapering phase. There was a significant increase in disease activity in the tapering-out group. Rheumatoid arthritis flares were more frequent in the tapering-out group, especially at the end of the observation period.
For the risk of infection with methotrexate, the authors cite two meta-analyses. Both are based almost exclusively on a randomized double-blind study published in 1999 (3) and state an increased relative risk of 1.3 and 1.25, respectively, as compared to placebo. Observational studies have mainly compared different disease-modifying therapies with each other. A case–control study from 1980 to 2003, for example, showed a significantly increased risk of pneumonia with methotrexate use as compared to other disease-modifying therapies that were common at the time, but overall hospital admissions for infections were not significantly increased (4).
For biologics, Mucke et al. state a rate of serious infectious events of 4 to 5 per 100 patient-years. In view of the long-term therapy required, this seems considerable. It would be interesting to know which infections were rated as severe, and whether this number must be expected even if the recommended precautions are observed. What is the rate in a control group? Are there differences between the biologics?
Footnotes
Conflict of interest statement:
The author declares that no conflict of interest exists.
References
- 1.Mucke J, Simon HU, Burmester GR. The safety of antirheumatic drugs. Dtsch Arztebl Int. 2022;119:81–87. doi: 10.3238/arztebl.m2021.0389. [DOI] [PubMed] [Google Scholar]
- 2.Burmester GR, Buttgereit F, Bernasconi C, et al. Continuing versus tapering glucocorticoids after achievement of low disease activity or remission in rheumatoid arthritis (SEMIRA): a double-blind, multicentre, randomised controlled trial. Lancet. 2020;396:267–276. doi: 10.1016/S0140-6736(20)30636-X. [DOI] [PubMed] [Google Scholar]
- 3.Strand V, Cohen S, Schiff M, et al. Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate. Arch Intern Med. 1999;159:2542–2550. doi: 10.1001/archinte.159.21.2542. [DOI] [PubMed] [Google Scholar]
- 4.Bernatsky S, Hudson M, Suissa S. Anti-rheumatic drug use and risk of serious infections in rheumatoid arthritis. Rheumatology (Oxford) 2007;46:1157–1160. doi: 10.1093/rheumatology/kem076. [DOI] [PubMed] [Google Scholar]