High dose chemotherapy and hematopoietic stem cell transplantation: a study of treatment preference in patients with rheumatoid arthritis and rheumatologists.

OBJECTIVE: Patients with intractable rheumatoid arthritis (RA) may benefit from treatment with high dose chemotherapy followed by rescue with autologous hematopoietic peripheral blood stem cell transplant (HSCT). We investigated whether the risks of this approach are acceptable to patients with RA and rheumatologists and whether risk taking by patients was associated with disease characteristics, socioeconomic variables, and/or personality traits.

METHODS: A survey in the outpatient clinic was conducted among 2 cohorts of 45 (cohort A) and 51 (cohort B) RA patients with active disease. Patients received information about the potential benefit of HSCT (2/3 chance of a good clinical response, 1/3 no response) and treatment related morbidity and mortality. Cure was assumed not to be a realistic perspective. Cohort A was asked to choose between their own disease state for an indefinite time or HSCT. Nonparametric tests were performed to evaluate putative predictive factors that led patients to accept transplant related mortality (TRM): swollen joint count, tender joint count, visual analog scale (VAS) measures of disease activity and pain, erythrocyte sedimentation rate, Health Assessment Questionnaire (HAQ), socioeconomic variables, RA Quality of Life Questionnaire (RAQoL), and the Life Orientation Test. Cohort B was asked to consider a worst case scenario with respect to their disease activity. The minimal duration of benefit was assessed, given a TRM of 0.01% and 2%. To evaluate treatment preference of physicians, 96 Dutch rheumatologists responded to a hypothetical clinical case analogous to the interviews with RA patients. The minimum duration of benefit was assessed, given a TRM of 2% and the maximal TRM acceptable to rheumatologists if duration of benefit was 2 years in 2/3 patients.

RESULTS: In cohort A, 5 of 45 patients were willing to accept risk of death. VAS disease activity (p = 0.006), VAS pain (p = 0.021), and HAQ (p = 0.05) were significantly higher in patients willing to accept risk of death. Religiosity (p = 0.093), a higher Ritchie Articular Index (p = 0.096), and low quality of life (by RAQoL) (p = 0.133) showed trends toward risk taking. In cohort B, 22 of 50 patients (44%) were willing to accept a risk of TRM related to HSCT. For the 22 patients the median required duration of benefit given a TRM of 2% was 5 years (range 1-15). Physicians also required a median duration of benefit of 5 years.

CONCLUSION: We evaluated risk taking in patients with RA and physicians based on a realistic perspective in which the tradeoff between short term risks and possible longterm benefit of HSCT was investigated. Based on current efficacy data for HSCT (2 years improvement in 2/3 patients), half the patients would accept the current TRM of 2%, based on registry results. Patients willing to accept TRM had higher VAS disease activity, VAS pain, and HAQ. Doctors were more willing to accept mortality in the treatment of RA.