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P343 Maintenance of deep remission in Crohn’s disease after switching from anti–TNF to ustekinumab.

Mantzaris, G.(1);Vraka, M.(1);Beka, H.(1);Georgiadi, T.(1);Albani, F.(1);Veretanos, C.(1);Mountaki, K.(1);Trikola, A.(1);Archavlis, E.(1);Christidou, A.(1);Manolakis, A.(1);Viazis, N.(1);Karampekos, G.(1);Philippidis, G.(1);Hatzievangelinou, C.(1);Tsatsa, A.(1);Georgiadou, A.(1);Panagopoulou, S.(1);

(1)Evaggelismos GHA, Gastroenterology, Athens, Greece

Background

Anti-TNF agents, infliximab (IFX) and adalimumab (ADL) are first line treatment for moderate-to-severe Crohn’s disease (CD) and for preventing post-operative recurrence of CD (CD-POR) following right hemicolectomy (RH). However, a considerable proportion of patients develop allergic reactions and/or paradoxical inflammation to anti-TNFs necessitating switching to out of class biologic despite deep remission. We aimed to assess whether ustekinumab (UST), an IL12/IL23 inhibitor, can maintain deep remission in these patients.

Methods

This prospective, single centre study enrolled CD patients with B1 phenotype or on POR preventive therapy who were in prolonged deep remission when became intolerable of anti-TNFs. Deep remission was defined as clinical (HBI<4), biomarker (normal CRP and faecal calprotectin [FC<150μg/dl]), and endoscopic remission (SES-CD≤2 or Rutgeerts’ score [RS]≤1). Patients received UST (6mg/kg iv followed by 90mg sc q8 weeks) and were followed every 2 months with HBI score calculation and routine laboratory tests. Ileocolonoscopy was performed at 1y after UST initiation and the SES-CD or the RS were calculated. Absence of deep remission was defined as clinical (HBI>5), or biomarker relapse or endoscopic recurrence (SES-CD>2 or RS≥2, respectively).    

Results

Twenty five patients (15 males), median age(range) 42(20-65)y were included. Seven patients had undergone RH, 6 had colitis and 12 had ileitis or ileocolitis; 13 patients had received ADL, 8 IFX and 4 both. Patients were in deep remission for 3.8 (2-10)y [median (range)]. Reasons for switching were severe psoriasis/proriasiform lesions (11), persistent arthralgias (10), infusion/injection reactions (2), anti-TNF-induced lupus erythematosus (2), sweet syndrome (1), and vasculitis (1). Two patients had more than one paradoxical inflammation. At baseline the median (range) CRP was 0.21mg/dl (0.10-0.40), FC 52μg/g (20-114). Trough levels for anti-TNFs in 15/25 patients were normal without antibodies. At 1-year post-switching endoscopic CD-POR was seen in 3/7 patients (RS≥2b) associated with biomarker relapse in 2 and clinical relapse in 1 patient. Of 18 patients with B1 phenotype deep remission was maintained in 15: two patients with infusion reactions to IFX relapsed and 1 patient developed endoscopic lesions in view of normal CRP but abnormal FC (SES-CD 6, 5 and 3, respectively). Paradoxical inflammation resolved in all 23 patients but de novo arthralgias developed in 2 patients. Thus, one year after switching to UST, 19/25 CD patients maintained deep remission.

Conclusion

UST seems to be a reliable therapeutic alternative for anti-TNF-dependent patients who have who cannot tolerate anti-TNFs.     

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