High dose chemotherapy followed by autologous peripheral blood stem cell transplantation or conventional pharmacological treatment for refractory rheumatoid arthritis? A Markov decision analysis

Objective. To evaluate the effect of high dose chemotherapy (HDC) followed by autologous hematopoietic stem cell transplantation (ASCT) in comparison to conventional pharmacological therapy in the treatment of patients with r efractory, progressively erosive rheumatoid arthritis (RA). Methods. Decision analysis using a Markov model with a 5.5 year time horizo n. Probabilities of transition towards 5 different health states, ranging f rom 70% improvement to death, were derived from published case reports, pat ient series, and expert panels, Quality of life (QOL) estimates were obtain ed from 2 RA clinical trials. Patients were hypothetical cohorts of 50-year -old female patients with progressively erosive, active RA, who failed trea tment with methotrexate, combination therapy, and tumor necrosis factor blo cking agents. Interventions were HDC + ASCT versus conventional pharmacolog ical treatment with a (combination) therapy of disease modifying antirheuma tic drugs. As main outcome measures, we included the number of quality adju sted life years (QALY) after HDC + ASCT compared to conventional therapy, S ensitivity analysis was performed to investigate the influence of treatment related mortality (TRM) and the influence of QOL during HDC + ASCT, and to assess the minimal desired effectiveness of HDC + ASCT for a given TRM of 1% and 10%, Results. HDC + ASCT and conventional pharmacological treatment were equally effective in the base-case analysis (3.48 vs 3.46 QALY), A TRM of less tha n 3.3% favored HDC + ASCT as the preferred treatment, The analysis showed t hat when TRM was set at 1%, a relatively short period of efficacy was suffi cient to remain the preferred strategy, whereas a TRM of 10% would require a sustained response for several years, Conclusion. This model predicted equally favorable effects of HDC + ASCT an d conventional therapy in the treatment of refractory RA in the base-case, The minor differences in terms of QALY seem to indicate that clinical decis ion making should be guided by patient preferences. However, better clinica l efficacy might be achieved by adaptation of the treatment regimen of HDC + ASCT and patient selection. The model supports the need for randomized cl inical trials and may contribute to an optimal study design.