Amit Assa1, Manar Matar2, Dan Turner3, Efrat Broide4, Batia Weiss5, Oren Ledder3, Anat Guz-Mark6, Firas Rinawi6, Shlomi Cohen7, Chani Topf-Olivestone8, Ron Shaoul9, Baruch Yerushalmi10, Raanan Shamir6. 1. The Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Hospital, Petach-Tikva, Israel; The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: dr.amit.assa@gmail.com. 2. The Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Hospital, Petach-Tikva, Israel. 3. The Juliet Keidan Institute of Pediatric Gastroenterology, Nutrition, Shaare Zedek Medical Center, The Hebrew University, Jerusalem, Israel. 4. The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Pediatric Gastroenterology Unit, Assaf Harofeh Medical Center, Zerifin, Israel. 5. The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Pediatric Gastroenterology Unit, Sheba Medical Center, Edmond and Lily Safra Childen's Hospital, Ramat-Gan, Tel-Hashomer, Israel. 6. The Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Hospital, Petach-Tikva, Israel; The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 7. The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Pediatric Gastroenterology Unit, "Dana-Dwek" Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. 8. Pediatric Gastroenterology Unit, Kaplan Medical Center, Rehovot, Israel. 9. Pediatric Gastroenterology Unit, Rambam Medical Center, Haifa, Israel. 10. Pediatric Gastroenterology Unit, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Abstract
BACKGROUND & AIMS: Proactive monitoring of drug trough concentrations and antibodies against drugs might help determine whether patients are likely to respond to treatment and increase efficacy. We investigated whether proactive drug monitoring is associated with higher rates of clinical remission in pediatric patients with Crohn's disease (CD). METHODS: We performed a nonblinded, randomized controlled trial of 78 children with CD (6-18 years old; 29% female; mean age, 14.3 ± 2.6 years) who had not received prior treatment with a biologic agent but had responded to adalimumab induction therapy, under scheduled monitoring of clinical and biologic measures (based on clinical factors and levels of C-reactive protein and fecal calprotectin), at pediatric gastroenterology units in Israel from July 2015 through December 2018. The patients were randomly assigned to groups that received proactive monitoring (trough concentrations measured at weeks 4 and 8 and then every 8 weeks until week 72, n = 38) or reactive monitoring (physicians were informed of trough concentrations after loss of response, n = 40). In both groups, doses and intervals of adalimumab were adjusted to achieve trough concentrations of 5 μg/mL. The primary endpoint was sustained corticosteroid-free clinical remission at all visits (week 8 through week 72). RESULTS: The primary endpoint was achieved by 31 children (82%) in the proactive group and 19 children (48%) in the reactive group (P = .002). Sixteen patients in the proactive monitoring group (42%) achieved a composite outcome of sustained corticosteroid-free remission, C-reactive protein ≤0.5 mg/dL, and level of fecal calprotectin ≤150 μg/g compared with 5 patients in the reactive monitoring group (12%) (P = .003). By week 72 of treatment, 33 patients in the proactive monitoring group had received adalimumab intensification (87%) compared with 24 patients in the reactive monitoring group (60%) (P = .001). CONCLUSIONS: In a randomized controlled trial of pediatric patients with CD, we found that proactive monitoring of adalimumab trough concentrations and adjustment of doses and intervals resulted in significantly higher rates corticosteroid-free clinical remission than reactive monitoring (measuring trough concentration after loss of response). Clinicaltrials.gov no.: NCT02256462.
RCT Entities:
BACKGROUND & AIMS: Proactive monitoring of drug trough concentrations and antibodies against drugs might help determine whether patients are likely to respond to treatment and increase efficacy. We investigated whether proactive drug monitoring is associated with higher rates of clinical remission in pediatric patients with Crohn's disease (CD). METHODS: We performed a nonblinded, randomized controlled trial of 78 children with CD (6-18 years old; 29% female; mean age, 14.3 ± 2.6 years) who had not received prior treatment with a biologic agent but had responded to adalimumab induction therapy, under scheduled monitoring of clinical and biologic measures (based on clinical factors and levels of C-reactive protein and fecal calprotectin), at pediatric gastroenterology units in Israel from July 2015 through December 2018. The patients were randomly assigned to groups that received proactive monitoring (trough concentrations measured at weeks 4 and 8 and then every 8 weeks until week 72, n = 38) or reactive monitoring (physicians were informed of trough concentrations after loss of response, n = 40). In both groups, doses and intervals of adalimumab were adjusted to achieve trough concentrations of 5 μg/mL. The primary endpoint was sustained corticosteroid-free clinical remission at all visits (week 8 through week 72). RESULTS: The primary endpoint was achieved by 31 children (82%) in the proactive group and 19 children (48%) in the reactive group (P = .002). Sixteen patients in the proactive monitoring group (42%) achieved a composite outcome of sustained corticosteroid-free remission, C-reactive protein ≤0.5 mg/dL, and level of fecal calprotectin ≤150 μg/g compared with 5 patients in the reactive monitoring group (12%) (P = .003). By week 72 of treatment, 33 patients in the proactive monitoring group had received adalimumab intensification (87%) compared with 24 patients in the reactive monitoring group (60%) (P = .001). CONCLUSIONS: In a randomized controlled trial of pediatric patients with CD, we found that proactive monitoring of adalimumab trough concentrations and adjustment of doses and intervals resulted in significantly higher rates corticosteroid-free clinical remission than reactive monitoring (measuring trough concentration after loss of response). Clinicaltrials.gov no.: NCT02256462.
Authors: John L Lyles; Aditi A Mulgund; Laura E Bauman; Weizhe Su; Lin Fei; Deepika L Chona; Puneet Sharma; Renee K Etter; Jennifer Hellmann; Lee A Denson; Phillip Minar; Dana M Dykes; Michael J Rosen Journal: Inflamm Bowel Dis Date: 2021-03-15 Impact factor: 5.325
Authors: Konstantinos Papamichael; Niels Vande Casteele; Jenny Jeyarajah; Vipul Jairath; Mark T Osterman; Adam S Cheifetz Journal: Am J Gastroenterol Date: 2021-05-01 Impact factor: 12.045