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P368 Ustekinumab in super-refractory Crohn´s disease patients

C. Herrera*, V. Robles, C. Jimenez, E. Navarro, F. Casellas, N. Borruel

Unitat Atenció Crohn-Colitis. Hospital Universitari Vall d'Hebron, Digestive System Research Unit, Barcelona, Spain

Background

Blockage of tumor necrosis factor(TNF) has been a major advancement in the therapy for Crohn's disease(CD). However up to 40% of patients do not achieve a response to induction with anti-TNF(primary non-responders) and of those who achieve a primary response, approximately 40% subsequently lose response. Medical therapy for active CD patient's who have lost response to currently approved medications is an unmet clinical need. Ustekinumab, a monoclonal antibody against the p40 subunit of interleukin-12/23 has demonstrated to be effective in inducing and maintaining remission in CD patients (Sandborn, NEJM2012). In Spain, its application is limited to compassionate use in refractory CD patients.

Methods

Patients with refractory CD previously treated at our institution with at least two anti-TNF agents and treated with Ustekinumab were enrolled. Data regarding activity of the disease prior and post induction therapy were analyzed. Induction dose was 3mg/kg subcutaneously followed by maintenance schedule of 90mg every 8 weeks (4 patients had an extra dose of 90 mg at week 4). Response to therapy was assessed at 8 weeks and at the end of follow-up and defined as a reduction >70 points from baseline CDAI, and clinical remission as CDAI<150 points.

Results

Eight patients received Ustekinumab for refractory CD. Six were female, half of them were non-smokers and median age was 39. Sixty-two percent of patients had ileocolonic involvement and behavior of CD was inflammatory in four, penetrating in three and stricturing in one patient (two patients had perianal involvement). All patients had previously received Infliximab and Adalimumab, and one patient had also received Certolizumab. All had failed Azathioprine and Methotrexate, and one patient also received Tacrolimus and two of them photoapheresis. Six patients had a primary non-response to the second or third antiTNF and two patients who had received IFX and ADA developed paradoxical psoriasis. Patients had a median CDAI score of 301[224-404] before treatment, 167[35-262] at week 8 after induction and 90[0-133] at the end of follow-up. Seven out of the eight patients had a clinical response to induction, and 3 of them(37,5%) were in clinical remission at week 8. Median follow-up on maintenance was 42 weeks and 6 patients are still receiving treatment and in clinical remission(75%). No serious adverse events were reported, the most common side affect was arthralgia referred by two patients.

Conclusion

Although our study included few patients, clinical Results suggest that Ustekinumab is an effective drug in maintaining remission in medium-term in CD patients super-refractory to immunomodulators and anti-TNF's. Efficacy of high induction doses must be confirmed in larger studies.