An open-label prospective randomized multicenter study of intensive versus weekly granulocyte and monocyte apheresis in active crohn’s disease

Abstract

BackgroundGranulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active Crohn’s disease (CD). However, with routine weekly therapy, it may take several weeks to achieve remission. This study was performed to assess clinical efficacy and safety of intensive GMA in patients with active CD.MethodsIn an open-label, prospective, randomized multicentre setting, 104 patients with CD activity index (CDAI) of 200 to 450 received intensive GMA, at two sessions per week (n = 55) or one session per week (n = 49). Clinical remission was defined as a CDAI score <150. Patients in each arm could receive up to 10 GMA sessions. However, GMA treatment could be discontinued when CDAI decreased to <150 (clinical remission level).ResultsOf the 104 patients, 99 were available for efficacy evaluation as per protocol, 45 in the weekly GMA group, and 54 in the intensive GMA group. Remission was achieved in 16 of 45 patients (35.6 %) in the weekly GMA and in 19 of 54 (35.2 %) in the intensive GMA (NS). Further, the mean time to remission was 35.4 ± 5.3 days in the weekly GMA and 21.7 ± 2.7 days in the intensive GMA (P = 0.0373). Elevated leucocytes and erythrocyte sedimentation rate were significantly improved by intensive GMA, from 8005/μL to 6950/μL (P = 0.0461) and from 54.5 mm/hr to 30.0 mm/hr (P = 0.0059), respectively. In both arms, GMA was well tolerated and was without safety concern.ConclusionsIn this study, with respect to remission rate, intensive GMA was not superior to weekly GMA, but the time to remission was significantly shorter in the former without increasing the incidence of side effects. UMIN registration # 000003666.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-015-0390-3) contains supplementary material, which is available to authorized users.

Combination Therapy With Intensive Granulocyte and Monocyte Adsorptive Apheresis Plus Ustekinumab in Patients With Refractory Crohn's Disease

“…Granulocyte and monocyte absorptive apheresis is available in Europe and Japan for the treatment of patients with active CD that may or may not be refractory to standard pharmacotherapy, including TNF‐α antagonists . GMA depletes activated leukocytes, particularly granulocytes and macrophages, thereby downregulating proinflammatory cytokine (IL‐1β and TNF‐α)‐induced inflammatory responses in peripheral blood mononuclear cells, resulting in amelioration of gut inflammation .…”

“…GMA depletes activated leukocytes, particularly granulocytes and macrophages, thereby downregulating proinflammatory cytokine (IL‐1β and TNF‐α)‐induced inflammatory responses in peripheral blood mononuclear cells, resulting in amelioration of gut inflammation . An open‐label prospective randomized study comparing the efficacy of intensive GMA with that of weekly GMA showed that no significant differences in remission rates between patients with intensive GMA (35.2%) and those with weekly GMA (35.6%), but time to remission was significantly shorter in the intensive GMA group (21.7 days) than in the weekly GMA group (35.4 days) without increasing the incidence of side‐effects . This suggests that GMA, which normalizes imbalances in immune profile in patients with CD, has strong and favorable impacts on the efficacy of UST.…”

“…Regarding endoscopic responses in the present study, 10‐week SES‐CD scores during combination therapy reflected no improvement in all three cases. No data have yet shown endoscopic improvements with intensive GMA monotherapy in active CD patients . However, a prospective cohort investigating the 52‐week efficacy and endoscopic outcomes of intensive GMA combined with thiopurines in corticosteroids‐ and TNF‐α biologic‐naïve patients with early‐diagnosed CD (mean CDAI, 260) showed that the rate of mucosal healing (SES‐CD = 0) at week 6 was 22.7% .…”

“…In Japan and Europe, GMA is another safe and non‐drug therapeutic option for patients with IBD refractory to pharmacological therapy . In addition, intensive GMA involving two sessions a week has recently been shown to be superior to routine weekly GMA in terms of time to remission in patients with refractory CD .…”

Optimizing the Use of Current Treatments and Emerging Therapeutic Approaches to Achieve Therapeutic Success in Patients with Inflammatory Bowel Disease

“…2) Crohn's disease Several reports have shown the efficacy of GMAA in patients with active CD. Based on data demonstrated that intensive GMAA is superior to weekly apheresis in the induction of remission for active UC, Yoshimura et al 38 performed an openlabel, prospective, randomized study to evaluate the clinical efficacy and safety of intensive GMAA in patients with active CD. The results of the study demonstrated that the time to remission was significantly shorter in CD patients treated with intensive GMAA than in those treated with weekly GMAA, despite the absence of a significant difference in remission rates between CD patients treated with intensive GMAA and those treated with weekly GMAA.…”