OP01 Withdrawal of infliximab or anti-metabolite therapy in Crohn’s Disease patients in sustained remission on combination therapy: A randomized unblinded controlled trial (SPARE)
LouisJ, E.(1);Resche-Rigon, M.(2);Laharie, D.(3);Satsangi, J.(4);Ding, N.(5);Preiss, J.(6);d'haens, G.(7);picon, L.(8);bossuyt, P.(9);vuitton, L.(10);irving, P.(11);bouhnik, Y.(12);viennot, S.(13);lamb, C.(14);pollock, R.(15);baert, F.(16);nachury, M.(17);mathurin, F.(18);Gilletta, C.(19);colombel, J.F.(20);hertervig, E.(21);
(1)CHU Liège- Sart Tilman, Department of Gastroenterology, Liège, Belgium;(2)Inserm U1077, Biostatistics, Paris, France;(3)CHU Bordeaux, Gastroenterology, Bordeaux, France;(4)John Radcliffe hospital, Gastroenterology, Oxford, United Kingdom;(5)St Vincent Hospital Melbourne, Gastrtoenterology, Melbourne, Australia;(6)Charite Berlin, Gastroenterology, Berlin, Germany;(7)AMC Amsterdam, Gastroenterology, Amsterdam, The Netherlands;(8)CHU Tours, Gastroenterology, Tours, France;(9)Imelda Hospital, Gastroenterology, Bonheiden, Belgium;(10)CHU Besancon, Gastroenterology, Besancon, France;(11)London-Guy's and Thomas, Gastroenterology, London, United Kingdom;(12)Hôpital Beaujon, Gastroenterology, Paris, France;(13)CHU Caen, Gastroenterology, Caen, France;(14)Royal Victoria Infirmary, Gastroenterology, Newcastle, United Kingdom;(15)St Georges' University Hospital, Gastroenterology, London, United Kingdom;(16)AZ Delta, Gastroenterology, Roeselare, Belgium;(17)CHU Lille, Gastroenterology, Lille, France;(18)CHU Amiens, Gastroenterology, Amiens, France;(19)CHU Toulouse, Gastroenterology, Toulouse, France;(20)Mount Sinai Hopsital, Gastroenterolgy, New York, United States;(21)skane university hospital, gastroenterology, Lund, Sweden;
Background
Combination therapy with infliximab and anti-metabolites is a standard option for patients with Crohn’s disease (CD). The implications of long term use of combination therapy may lead patients and clinicians to contemplate treatment de-escalation once steroid-free remission has been achieved. The aim of our study was to assess the relapse rates and time spent in remission over 2 years, after withdrawal of infliximab or anti-metabolite compared to continuation of combination therapy.
Methods
CD patients treated with a combination therapy of infliximab (IFX) and anti-metabolite > 8 months and in sustained steroid-free remission > 6 months were recruited in 64 centers in France, United Kingdom, Belgium, Sweden, Australia, Germany and The Netherlands. Patients were randomized into 3 arms - continuing combination therapy (arm A); stopping IFX (arm B); or stopping anti-metabolite (arm C). In case of a relapse [defined by CDAI and an objective marker of inflammation (CRP or fecal calprotectin)], patients were retreated by resuming infliximab in arm B or the anti-metabolite in arm C, according to a pre-defined scheme, including optimization of IFX up to 10 mg/Kg if necessary in all arms. The two co-primary endpoints were the relapse rate and mean survival time spent in remission over 2 years. A major secondary endpoint was treatment failure (complications or not recapturing remission).
Results
254 patients were screened, 211 randomized, 5 withdrew consent and 1 was lost to follow-up, leaving 205 patients for the analysis - 67 randomized to arm A, 71 to arm B and 67 to arm C. Demographic and clinical characteristics are shown in Table 1. The two-year relapse rates were 14% (IC95%: 4-23%) in arm A, 40% (IC95%: 28-51%) in arm B, and 10% (IC95%: 2-18%) in arm C (p=0.0003 arm B vs arm A and <0.0001 arm B vs arm C) (figure 1). The time spent in remission was 1.91 yrs (IC95%: 1.83-1.99), 1.89 yrs (IC95%: 1.82-1.96) and 1.93 yrs (IC95%: 1.86-2.00) in arm A, B and C, respectively. Out of the 39 relapsers, 28 were retreated/optimized. Remission was achieved in 1/2 retreated patients in arm A, 22/23 in arm B and 2/3 in arm C. Treatment failure was observed in 4/67, 4/71 and 3/67 patients, in these three arms, respectively. No malignancy was observed, one tuberculosis in arm C and two severe infections (pneumonia and viral pericarditis) in arm B.
Conclusion
Infliximab withdrawal, but not antimetabolite withdrawal, was associated with a significantly higher risk of relapse than continuation of combination therapy. Almost all patients who stopped IFX achieved rapid remission when resuming treatment. The time spent in remission over 2 years was similar across groups.