 |
|
|
 |
Is Once a Week Enough? To the Editor: Etanercept, infliximab, and adalimumab, are the 3 anti-tumor necrosis factor-a (TNF-a) agents widely used for the treatment of aggressive rheumatoid arthritis (RA). Etanercept (Enbrel) is a fully humanized soluble recombinant TNF receptor p75 Fc fusion protein1, which until recently was routinely given by subcutaneous injection 25 mg twice weekly. Etanercept 50 mg once weekly was licensed in the UK for the treatment of RA on April 28, 2005. The use of etanercept 50 mg once weekly in patients with RA2 and ankylosing spondylitis3 has been shown to have similar clinical outcomes, safety, efficacy, and pharmacokinetic profiles as compared to etanercept 25 mg twice weekly2,3. This preparation is becoming more popular, as patients only need injections once weekly. We conducted an observational study during the summer of 2006 at the Rheumatology Department, Stoke Mandeville Hospital, Aylesbury, UK. We retrospectively audited the clinical notes of patients diagnosed with RA who had been treated successfully with etanercept 25 mg twice weekly and subsequently switched to 50 mg once weekly. We set out to prove the null hypothesis that there was no difference in clinical outcome regardless of the etanercept dosing regime used in our cohort of patients. The cohort consisted of 15 patients, all female. The mean age was 50.3 years (range 36–60). These patients had been successfully treated with etanercept 25 mg twice weekly in accord with British Society for Rheumatology guidelines4. Disease Activity Score-28 (DAS-28)4-scores were analyzed before and 3 months after switching to etanercept 50 mg once weekly. All patients in the cohort had been switched to the once-weekly regimen due to personal choice. Five patients (31.3%) were found to deteriorate when switched to etanercept 50 mg once weekly. The mean DAS-28 was 3.19 (SD ± 1.20) while taking 25 mg twice weekly, and 5.48 (SD ± 1.16) while taking 50 mg once weekly. The increase in DAS-28 score was statistically significant (p = 0.019). Statistically significant increases were seen in both the swollen joint score (p < 0.009) and visual analog scale (VAS) pain score (p < 0.041), but not the erythrocyte sedimentation rate (ESR; p < 0.067) or tender joint count (p < 0.065). In 11 patients (68.7%), disease activity remained stable when switched to the once-weekly regimen. Mean DAS-28 scores were 3.57 (SD ± 1.21) and 3.07 (SD ± 1.59) while taking 25 mg twice weekly and 50 mg once weekly, respectively. The reduction in DAS-28 score was not statistically significant (p = 0.181). The 5 patients who deteriorated switched successfully back to their original dosing regime. Our results show that one-third of patients treated with etanercept 25 mg twice weekly for RA deteriorated when switched to etanercept 50 mg once weekly. One argument would be that the patients' deterioration could be due to the patients' perception of having only one injection a week, when previously they were having 2. However, studies have shown that the maximum influence that the VAS score can have on the DAS-28 is 1.2, and that there was no change in the overall management when the VAS was excluded from the DAS-28 calculation5. Despite both etanercept dosing regimes satisfying the primary requirements for bioequivalence testing6, comparable clinical outcomes were not seen in our small cohort of patients. The study group used by van der Heijde, et al3 and Keystone, et al2 was interestingly etanercept treatment-naive, in contrast to our cohort of patients. This may be the reason for the disparity in the results of our study. A larger study group may also have shown statistically significant changes in the ESR and tender joint count. Further, we can postulate from our results that patients who fail to respond adequately to etanercept 50 mg once weekly may respond to etanercept 25 mg twice weekly. Our experience rejects the null hypothesis. This small observational study suggests that patients well controlled on etanercept 25 mg twice weekly may experience loss of disease control if they considered switching to etanercept 50 mg once weekly. Larger studies are needed in this area, but clinicians should be aware of our interesting and relevant findings, and proceed with caution if considering switching a patient with RA controlled taking etanercept 25 mg twice weekly to 50 mg weekly. SANDEEP BAWA, MBChB, MRCP, Specialist Registrar, Rheumatology, Department of Rheumatology, Nuffield Orthopaedic Centre, Oxford; JACKIE HALL, RGN, Specialist Nurse Rheumatology; SALLY EDMONDS, MD, FRCP, Consultant Rheumatologist; MIKE WEBLEY,MB, FRCP, Consultant Rheumatologist, Department of Rheumatology, Stoke Mandeville Hospital, Aylesbury, Buckinghamshire, United Kingdom. Address reprint requests to Dr. Bawa; e-mail: sandeep.bawa@noc.anglox.nhs.uk 2. Keystone EC, Schiff MH, Kremer JM, et al. Once-weekly administration of 50 mg etanercept in patients with active rheumatoid arthritis: Results of a multicentre, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2004;50:353-63. [MEDLINE] 3. Van der Heijde, Da Silva JC, Dougados M, et al. Etanercept 50 mg once weekly is as effective as 25 mg twice weekly in patients with ankylosing spondylitis. Ann Rheum Dis 2006;65:1572-7. [MEDLINE] 4. Ledingham J, Deighton C. Update on the British Society for Rheumatology guidelines for prescribing TNF alpha blockers in adults with rheumatoid arthritis (update of previous guidelines of April 2001). Rheumatology Oxford 2005;44:157-63. Erratum in: Rheumatology Oxford 2006;45:1170. [MEDLINE] 5. Bawa S, Fowler L, Bradlow A. Comparison between DAS 28 4-score and 3-score -- would it influence patient eligibility for, or evaluation of response to anti-TNF X. Rheumatology Oxford 2005;44:i99. 6. Nestorov I, Lescale-Matys L, Salfi M, et al. Pharmacokinetics of a single 50 mg etanercept dose in healthy volunteers [abstract]. Arthritis Rheum 2003;48 Suppl:S141. |