Correspondence

New Drugs for Rheumatoid Arthritis

N Engl J Med 2004; 351:937-938August 26, 2004

Article

To the Editor:

In an examination of the data that support the use of anti–tumor necrosis factor (TNF) drugs for rheumatoid arthritis, as reviewed by O'Dell (June 17 issue)1 and by Olsen and Stein (May 20 issue),2 one critical point is that there has been just a single randomized trial of infliximab and adalimumab (in which the new agent plus methotrexate was compared with methotrexate alone) and there have been only two trials of etanercept (one very recent3 and therefore not mentioned by Olsen and Stein). In addition, the number of patients enrolled in these trials was small (the number of patients receiving the anti-TNF drug plus methotrexate was 82 for infliximab, 67 for adalimumab, and 59 and 231 for etanercept). On the one hand, because the experimental data supporting the use of biologic agents are based on small patient populations, one could question whether the effectiveness of an agent has been established conclusively. On the other hand, these biologic agents are currently prescribed for thousands of patients and so are widely recognized as the standard therapy for such patients.

To increase the statistical power of the efficacy data for anti-TNF agents, we carried out a meta-analysis (Table 1Table 1Meta-Analysis of Data on the Efficacy of Anti-TNF Drugs.). The results show a high significance favoring the anti-TNF agents. The calculations of publication bias, based on the end point of the response criteria of the American College of Rheumatology for an improvement of 20 percent (ACR20), indicate that a null two-group trial with at least 3800 patients per group would be needed to reverse the significance of the results of our meta-analysis to nonsignificance. For ACR50, 7500 patients would be required, and for ACR70 7000 patients. Alternatively, to generate this reversal, 47 null trials (each with a sample size similar to those in the published trials) would be needed on the basis of our ACR20 results; 60 trials and 37 trials would be needed on the basis of our ACR50 and ACR 70 results.

The high significance of our meta-analysis and the results of our calculations of publication bias support the conclusion that treatment with an anti-TNF drug plus methotrexate is more effective than methotrexate alone and might therefore be considered as standard therapy for patients with rheumatoid arthritis. This conclusion implies that in future randomized trials, the control group should no longer include subjects treated with methotrexate alone.

Andrea Messori, Pharm.D.
Benedetta Santarlasci, Pharm.D.
Monica Vaiani, Pharm.D.
Laboratorio SIFO di Farmacoeconomia, 50136 Florence, Italy
andreamessori@interfree.it

Dr. Messori reports having received lecture fees from Johnson & Johnson; fees for running educational programs from Ferring, Eli Lilly, and several nonprofit scientific societies; and funds for research or for members of staff from Eli Lilly, Sigma Tau, and Roche.

4 References

1. 1

   O'Dell JR. Therapeutic strategies for rheumatoid arthritis. N Engl J Med 2004;350:2591-2602
   Full Text | Web of Science | Medline

2. 2

   Olsen NJ, Stein CM. New drugs for rheumatoid arthritis. N Engl J Med 2004;350:2167-2179
   Full Text | Web of Science | Medline

3. 3

   Klareskog L, van der Heijde D, de Jager JP, et al. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet 2004;363:675-681
   CrossRef | Web of Science | Medline

4. 4

   Messori A, Trippoli S, Vaiani M, Gorini M, Corrado A. Bleeding and pneumonia in intensive care patients given ranitidine and sucralfate for prevention of stress ulcer: meta-analysis of randomised controlled trials. BMJ 2000;32:1103-1106
   CrossRef | Web of Science

Citing Articles (7)

Citing Articles

1. 1

   Ronald Moskovich. 2012. Rheumatoid arthritis. , 473-479.
   CrossRef

2. 2

   Stephen M Roth, E Jeffrey Metter, Shari Ling, Luigi Ferrucci. (2006) Inflammatory factors in age-related muscle wasting. Current Opinion in Rheumatology 18:6, 625-630
   CrossRef

3. 3

   R. S. Gaston, G. M. Danovitch, R. A. Epstein, J. P. Kahn, A. J. Matas, M. A. Schnitzler. (2006) Limiting Financial Disincentives in Live Organ Donation: A Rational Solution to the Kidney Shortage. American Journal of Transplantation 6:11, 2548-2555
   CrossRef

4. 4

   Laura Coleman. 2005. Rheumatoid Cachexia. , 165-179.
   CrossRef

5. 5

   Jan S??rensen, Lis S Andersen. (2005) The Case of Tumour Necrosis Factor-?? Inhibitors in the Treatment of Rheumatoid Arthritis. PharmacoEconomics 23:3, 289-298
   CrossRef

6. 6

   (2004) New Drugs for Rheumatoid Arthritis. New England Journal of Medicine 351:25, 2659-2661
   Full Text

7. 7

   (2004) Rheumatoid Arthritis. New England Journal of Medicine 351:13, 1360-1361
   Full Text

Letters