P518 Remission induction in corticosteroid naïve children and adolescents with ulcerative colitis by adsorptive leucocytapheresis as monotherapy or in combination with low dose prednisolone after failure of first-line medications
Tanaka T.*1, Goishi H.1, Kajihara T.1, Akagi M.1, Saniabadi A.2, Miura T.1
1Akitsu Hospital, Gastroenterology, Hiroshima, Japan 2JIMRO, Takasaki, Japan
In patients with active ulcerative colitis (UC), myeloid lineage leucocytes are known to be elevated with activation behaviour including the CD14+CD16+ monocyte phenotype, which is a major source of tumour necrosis factor-α (Belge, et al. J Immunol 2002). Therefore, selective depletion of myeloid leucocytes by adsorptive granulocyte/monocyte apheresis (GMA) with an Adacolumn should promote remission, or enhance drug efficacy. Potentially, GMA should be a relevant option in paediatrics and adolescents settings where drug therapy may have limitations.
Between 2010 and 2015, 30 consecutive ulcerative colitis (UC) patients, age 11–19 years, body weight 33–55.5kg were given mesalazine (n=23) or sulphasalazine (n=7) as first-line medication. Twenty patients relapsed or did not respond and received GMA with the Adacolumn, at 2 sessions in the first week, then weekly, up to 11 sessions. Patients who achieved ≥5 decrease in the clinical activity index (CAI) continued with GMA while non-responders received GMA in combination with prednisolone (PSL, 0.5 to 1.0mg/kg bodyweight). At entry and week 12, patients were clinically and endoscopically evaluated with each patient serving as her or his own control.
At entry, all 30 patients were corticosteroid naïve and none had deep colonic UC lesions or extensive loss of the mucosal tissue at the affected sites (GMA non-responder features). Ten patients achieved stable remission with the first-line medications and did not receive GMA. Six patients did not respond well to the first 5 GMA sessions and received PSL together with GMA, while 12 patients responded well to GMA with stable remission and 2 withdrew to receive high dose PSL (up to 2mg/kg). At entry, the average CAI was 14.2±0.4, range 11–17, and the average endoscopic index was 9.2±0.4, range 7–11. The corresponding values at week 12 were 2.1±0.2 range 1–4 (p<0.001) and 2.4±0.2, range 1–4 (p<0.001). PSL was tapered to 0mg within 3 months. Therefore, at week 12, all 30 patients were in clinical remission, majority with mucosal healing.
In this investigation, GMA in young corticosteroid naïve patients with active UC refractory to the first-line medications was associated with clinical remission and mucosal healing, while in non-responders to GMA monotherapy, addition of a low dose PSL enhanced the efficacy of GMA and tapering of PSL was not associated with UC relapse. Therefore, the majority of young steroid naïve UC patients who fail to respond to first-line medications should respond well to GMA and be spared from pharmacological intervention. Additionally, GMA has a good safety profile, which is a very favoured feature in growing patients.