Morbidity and mortality in rheumatoid arthritis patients with prolonged and profound therapy-induced lymphopenia

Objective. Therapies that deplete lymphocytes often improve symptoms in pat ients with otherwise refractory autoimmune disease but may result in long-t erm lymphopenia, the consequences of which are uncertain. To assess the imp act of prolonged lymphopenia on morbidity and mortality, we studied patient s who had previously received lymphocytotoxic monoclonal antibody (mAb) the rapy for rheumatoid arthritis (RA). Methods. Fifty-three patients who received the lymphocytotoxic mAb CAMPATH- 1H between 1991 and 1994 in the United Kingdom were assessed for mortality and infectious and malignant morbidity, by interview and case-note review. In addition, patients were monitored via the National Health Service Centra l Registry, to verify notification of death. Peripheral blood lymphocyte su bsets were analyzed by flow cytometry. A retrospective, matched-cohort stud y of mortality was also performed with 102 control subjects selected from t he European League Against Rheumatism database, which comprises patients wi th rheumatic disorders who have received immunosuppressive drugs. Results. There was profound and persistent peripheral blood lymphopenia in the mAb-treated patients, affecting predominantly the CD4+ subset. Median C D4+, CD8+, and CD19+ peripheral blood lymphocyte counts at 73-84 months aft er therapy were 185 cells/mul, 95 cells/mul, and 115 cells/mul, respectivel y. At a median followup of 71 months (range 14-90), 13 patients had died (2 4.5%), compared with 18% of the matched controls, providing a mortality rat e ratio of 1.45 (95% confidence interval 0.65-3.13). During 283 patient-yea rs of followup, there were 36 infections classified as major (12.7 per 100 patient-years). The causes of death and the spectrum of infections document ed were similar to those expected in a hospital-based RA cohort. Patients w ho received more than 1 course of therapy had more severe lymphopenia than did patients who received a single course, but this did not have an impact on mortality, or morbidity. Conclusion. Despite the occurrence of profound and long-lasting lymphopenia following treatment with antilymphocyte mAb therapy for RA, this therapy i s not associated with a large excess of mortality nor with an unusual spect rum of infections, at least during a medium-term period of followup. These data are also relevant to patients receiving lymphocytotoxic mAb therapy fo r other indications, and to patients receiving other lymphodepleting therap ies such as autologous stem cell transplantation.