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Morbidity and mortality in rheumatoid arthritis patients with prolonged therapy-induced lymphopenia: Twelve-year outcomes

Lookup NU author(s): Dr Alice Lorenzi, Professor John IsaacsORCiD



Objective. To assess immunologically relevant outcomes in a cohort of rheumatoid arthritis (RA) patients with prolonged therapy-induced lymphopenia. Methods. Morbidity (infection or malignancy) and mortality were assessed in 53 RA patients who were treated with the lymphocytotoxic monoclonal antibody alemtuzumab between 1991 and 1994. Data were obtained by interview, medical record review, and Office for National Statistics mortality monitoring. Lymphocyte subsets were enumerated by flow cytometry. A retrospective, matched-cohort study of mortality was performed with 102 control subjects selected from the European League Against Rheumatism database of patients with rheumatic disorders. Results. Lymphopenia persisted in the patients: median CD3 + CD4+, CD3+CD8+, CD19+, and CD56+ lymphocyte counts measured at a median fol-lowup of 11.8 years from the first administration of alemtuzumab were 0.50 × 109/liter, 0.26 × 109/liter, 0.11 × 109/liter, and 0.09 × 109/liter, respectively. Twenty-seven of 51 cases and 46 of 101 controls with available data had died, yielding a mortality rate ratio of 1.20 (95% confidence interval 0.72-1.98). Causes of death were similar to those that would be expected in a hospital-based RA cohort. No opportunistic infections were noted, and only 3 infections were documented following 36 elective orthopedic procedures. Conclusion. Despite continued lymphopenia 11.8 years after therapy, our patient cohort did not exhibit excess mortality or unusual infection-related morbidity, and surgery was well tolerated. These data should be reassuring for clinicians and patients who are considering lymphocytotoxic or other immunomodulatory therapy for RA. © 2008, American College of Rheumatology.

Publication metadata

Author(s): Lorenzi A, Clarke A, Wooldridge T, Waldmann H, Hale G, Symmons D, Hazleman B, Isaacs J

Publication type: Article

Publication status: Published

Journal: Arthritis & Rheumatism

Year: 2008

Volume: 58

Issue: 2

Pages: 370-375

ISSN (print): 0004-3591

ISSN (electronic): 1529-0131

Publisher: American College of Rheumatology


DOI: 10.1002/art.23122

PubMed id: 18240243


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Funder referenceFunder name
Arthritis Research UK
G7904009Medical Research Council