Swapping Versus Dose Optimization in Patients Losing Response to Adalimumab With Adequate Drug Levels

Archive ouverte

Roblin, Xavier | Genin, Capucine | Nancey, Stéphane | Williet, Nicolas | Veyrard, Pauline | Boschetti, Gilles | Phelip, Jean-Marc | Berger, Anne-Emmanuelle | Killian, Martin | Waeckel, Louis | Flourie, Bernard | Paul, Stéphane

Edité par CCSD ; Lippincott, Williams & Wilkins -

International audience. Abstract Background In cases of loss of response due to mechanistic failure under antitumor necrosis factor agents, it is recommended to switch to another class of biologics. Two different strategies were compared in patients with inflammatory bowel disease (IBD) who were treated with nonoptimized adalimumab (ADA) and experienced a loss of response despite therapeutic trough levels of adalimuma—either ADA dose optimization or switching to vedolizumab or ustekinumab. Methods Patients under maintenance therapy with ADA monotherapy (40 mg every 14 days) and who experienced a secondary loss of response with trough levels > 4.9 μg/mL were included prospectively in this nonrandomized study. The primary end point was the survival rate without therapeutic discontinuation after ADA dose optimization or switching to another class of biologics. Results Adalimumab was optimized (n = 61 patients, 42 Crohn’s disease, 19 ulcerative colitis) or swapped for vedolizumab (n = 40, 20 ulcerative colitis) or ustekinumab (n = 30, 30 Crohn’s disease). At 24 months, 11 out of 70 patients (14.8%) in the swap group discontinued treatment compared with 36 out of 61 (59.6%) patients in the optimization group (P < 0.001). The median time without therapeutic discontinuation was significantly longer in the swap group (>24 months) than in the optimization group (13.3 months, P < 0.001). In the optimization group, treatment discontinuation was positively associated with baseline fecal calprotectin >500 μg/g (HR, 3.53; 95% CI, 1.16–10.72; P = 0.026) and inversely associated with variation of trough levels of adalimumab (>2 µg/mL from baseline to week 8 after optimization; HR, 0.51; 95% CI, 0.13–0.82; P = 0.03). In the swap group, no factor was associated with treatment discontinuation. Conclusion In IBD patients under ADA maintenance therapy who experience a secondary loss of response and in whom trough levels are >4.9µg/mL, swapping to another class is better than optimizing ADA, which is, however, appropriate in a subgroup of patients.

Consulter en ligne

Suggestions

Du même auteur

Serum calprotectin is useful to confirm inflammatory bowel disease activity but not to predict relapse

Archive ouverte | Veyrard, Pauline | CCSD

International audience. Aim: Serum calprotectin (SC), a novel biomarker of inflammatory bowel diseases (IBD), has been recently investigated with conflicting results. The purpose of this study was to assess the abil...

No Difference of Adalimumab Pharmacokinetics When Dosed at 40 mg Every Week or 80 mg Every Other Week in IBD Patients in Clinical Remission After Adalimumab Dose Intensification

Archive ouverte | Paul, Stéphane | CCSD

International audience. IntroductionThe pharmacokinetic equivalence of dose intensification with adalimumab (ADA) 80 mg every other week (EOW) compared to weekly 40 mg has only been supported by modeling systems. Ai...

Addition of azathioprine to the switch of anti-TNF in patients with IBD in clinical relapse with undetectable anti-TNF trough levels and antidrug antibodies: a prospective randomised trial

Archive ouverte | Roblin, Xavier | CCSD

International audience. Objectives In patients with IBD experiencing an immune-mediated loss of response (LOR) to antitumour necrosis factor (anti-TNF), algorithms recommend a switch of anti-TNF without immunosuppre...

Chargement des enrichissements...