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Long-term survival after lymphocytotoxic monoclonal antibody therapy for rheumatoid arthritis
Arthritis Research & Therapy volume 7, Article number: P46 (2005)
In the early 1990s, we used the monoclonal antibody alemtuzumab (MabCampath, Schering AG, Berlin, Germany) to treat patients with refractory rheumatoid arthritis. This treatment provided temporary relief of symptoms but was associated with long-term lymphopenia, particularly of T lymphocytes . We continue to follow these patients to exclude any adverse effects of their long-term lymphopenia.
The objective of the current study was to compare 10-year mortality in this patient cohort with mortality in a control patient cohort.
Fifty-three rheumatoid arthritis patients that received alemtuzumab (median dose, 172 mg; range, 1–420 mg) between 1991 and 1994 (cases) were monitored via the Office for National Statistics Central Registry, to ensure notification of death. A retrospective, matched-cohort study of mortality was performed with 102 control subjects selected from the European League Against Rheumatism database. This database comprises patients with rheumatic disorders who have received immunosuppressive drugs, usually cyclophosphamide or azathioprine.
Median (range) duration of follow-up was 10.29 (1.27–12.15) years for cases and 10.35 (1.18–12.14) years for controls. There were 20 deaths among the cases compared with 37 among the controls. This provided a mortality rate of 0.045 deaths per person per year for the cases and 0.041 deaths per person per year for the controls. The mortality rate ratio was 1.10 (95% confidence interval, 0.61–1.95). There was no significant difference in survival between the two groups (P = 0.73, log-rank test). Figure 1 illustrates Kaplan–Meier survival plots for cases and controls. The causes of death in the cases reflected those expected in a hospital-based rheumatoid arthritis cohort. Median time (range) from treatment to death for cases was 5.9 (1.3–11.7) years. Mortality did not differ according to total dose of alemtuzumab or the number of courses received.
Despite long-term lymphopenia, there was no excess mortality in recipients of alemtuzumab at a median follow-up of 10.3 years from treatment.
Isaacs JD, Greer S, Sharma S, Symmons D, Smith M, Johnston J, Waldmann H, Hale G, Hazleman BL: Morbidity and mortality in rheumatoid arthritis patients with prolonged and profound therapy-induced lymphopenia. Arthritis Rheum. 2001, 44: 1998-2008. 10.1002/1529-0131(200109)44:9<1998::AID-ART348>3.0.CO;2-T.
This work was supported by Ilex Oncology, Inc. and the Arthritis Research Campaign
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Isaacs, J., Clarke, A., Hazleman, B. et al. Long-term survival after lymphocytotoxic monoclonal antibody therapy for rheumatoid arthritis. Arthritis Res Ther 7 (Suppl 1), P46 (2005). https://doi.org/10.1186/ar1567
- Rheumatoid Arthritis
- Rheumatoid Arthritis Patient
- Excess Mortality
- Rheumatic Disorder