Cyclophosphamide Pulse Therapy in Severe Refractory Crohn's Disease: A Retrospective Multicenter Case Series

Abstract

Background and Aims: In Crohn's disease (CD) patients still remain refractory to current regimens, including biologicals. Previous data from small single-center studies indicated cyclophosphamide pulse therapy (CPT) to be effective for induction of remission at least in steroid-refractory cases. The aim of the present study was to study the efficacy and safety of CPT in mainly tumor necrosis factor (TNF)-refractory complicated CD patients. Methods: Patients with refractory CD undergoing CPT were identified in 13 centers of the German IBD Study Group and retrospectively registered. In total, 41 patients (12 male, 29 female, median age 36 years, range 18-72 years) were included for analysis. Seventy-eight percent of these had previously been treated with thiopurines and 90% had previously received anti-TNF antibodies. Former steroid treatment was found throughout the cohort. Results: Patients received a median number of 5 (1-13) pulses every 28 (13-54) days in a period of 120 (12-411) days. A median dose of 766 (600-1,200) mg and a median cumulative dose of 4,500 (750-9,750) mg was given. A clinical response (reduction in the Harvey-Bradshaw Index [HBI] ≥2 points) was found in 68% of the patients and clinical remission (HBI <5 points) in 32%. Steroids could be reduced from 31 to 12 mg per day over all patients. Side effects were recorded in 71% (n = 29) of the patients. Three patients terminated CPT due to side effects. No patient died. Conclusion: Our data point to CPT as a therapeutic alternative for induction of remission in patients with severe refractory courses of CD including TNF antagonists. CPT might serve as bridging for maintenance treatment.

HLA -A, -C, -B, -DRB1, -DQB1 and -DPB1 allele and haplotype frequencies in 4514 healthy Norwegians

“…Two female patients in mid-forties experienced menopause during follow-up, possibly a side-effect of cyclophosphamide. These adverse effects, compatible with reports from cyclophosphamide treatment in established AID [245,246] are not negligible, although temporary. Importantly, they should be interpreted in the light of the potential long lasting clinical improvement for many patients.…”

Management of refractory inflammatory bowel disease

“…Numerous other medications have been studied in IBD, mostly with less success compared with traditional agents, either due to safety concerns or a relative lack of efficacy. Cyclophosphamide has been studied in TNF-refractory Crohn's disease with clinical response and remission observed in 68 and 32% of patients, respectively, although its use was limited by a high rate of adverse events [21]. In a meta-analysis that included two RCTs, thalidomide resulted in clinical response and remission in 69.3 and 51.5% of cases, respectively, with endoscopic improvement in 69.7% [22]; however, this agent remains challenging to obtain given its troubled history.…”