Managing Crohn’s disease with the Jak-inhibitor, Upadacitinib
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on July 3rd, 2023
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Many immune cells utilize the JAK-STAT pathway to induce a pro-inflammatory reaction; thus, inhibition of these proteins can reduce the severity of Crohn’s disease. Upadacitinib is a Jak inhibitor that had previously been approved to manage atopic dermatitis and rheumatoid arthritis. Thus, a study had been conducted to assess the efficacy of upadacitinib in treating Crohn’s disease
The phase 3 clinical trial included a total of 1021 participants, divided into two study cohorts that were recruited at different times and monitored independently. The patients were diagnosed with moderate-to-severe Crohn’s disease and had experienced 4 or more daily episodes of loose/soft stool accompanied with severe abdominal pain. These patients were randomly assigned to receive either an oral placebo or 45 mg of oral upadacitinib daily. Usage of other immunosuppressants, except for methotrexate and glucocorticoids, was stopped to clearly show the effect of upadacitinib. The Crohn’s Disease Activity Index (CDAI) was utilized for clinical assessment, and endoscopic outcome was determined based on the Simple Endoscopic Score for Crohn’s Disease (SES-CD) standard. After 12 weeks of treatment, clinical remission was reported by approximately half of those who were treated with upadacitinib; whereas, this clinical effect was only reported in less than 30% of those in the placebo group. The benefit is even more significant when comparison was made based on endoscopic observation: improvement to the lower gastrointestinal tract was observed in around 40% of those who were treated with upadacitinib, which is significantly higher than the 10% in the placebo group.
In those who were clinically benefited by upadacitinib in the two original studies, some were invited to join a subsequent study. This maintenance trial included 502 participants and they were given a daily oral regiment of either the placebo or 2 dose levels of upadacitinib (15 mg or 30 mg). After 52 weeks of treatment, the researchers concluded that the higher 30-mg dose was the most effective at inducing clinical remission and improving the lower gastrointestinal mucosa. After the safety results of all three studies were combined, the researchers found that the high 45-mg and 30-mg upadacitinib dose lead to a higher incidence of herpes zoster infection. The 30-mg upadacitinib dose, possibly due to longer treatment time, caused more episodes of neutropenia and hepatic complications. There was little difference between the rate of adverse events reported by those who were treated with 15 mg of upadacitinib and the placebo group. In conclusion, 45 mg of upadacitinib can be effectively used to manage Crohn’s disease, with the maintenance dose can be adjusted if needed. The researchers noted that a 5-year study is being conducted to investigate the long-term effects and if upadacitinib can lead to rare and long-latency adverse events.
The phase 3 clinical trial included a total of 1021 participants, divided into two study cohorts that were recruited at different times and monitored independently. The patients were diagnosed with moderate-to-severe Crohn’s disease and had experienced 4 or more daily episodes of loose/soft stool accompanied with severe abdominal pain. These patients were randomly assigned to receive either an oral placebo or 45 mg of oral upadacitinib daily. Usage of other immunosuppressants, except for methotrexate and glucocorticoids, was stopped to clearly show the effect of upadacitinib. The Crohn’s Disease Activity Index (CDAI) was utilized for clinical assessment, and endoscopic outcome was determined based on the Simple Endoscopic Score for Crohn’s Disease (SES-CD) standard. After 12 weeks of treatment, clinical remission was reported by approximately half of those who were treated with upadacitinib; whereas, this clinical effect was only reported in less than 30% of those in the placebo group. The benefit is even more significant when comparison was made based on endoscopic observation: improvement to the lower gastrointestinal tract was observed in around 40% of those who were treated with upadacitinib, which is significantly higher than the 10% in the placebo group.
In those who were clinically benefited by upadacitinib in the two original studies, some were invited to join a subsequent study. This maintenance trial included 502 participants and they were given a daily oral regiment of either the placebo or 2 dose levels of upadacitinib (15 mg or 30 mg). After 52 weeks of treatment, the researchers concluded that the higher 30-mg dose was the most effective at inducing clinical remission and improving the lower gastrointestinal mucosa. After the safety results of all three studies were combined, the researchers found that the high 45-mg and 30-mg upadacitinib dose lead to a higher incidence of herpes zoster infection. The 30-mg upadacitinib dose, possibly due to longer treatment time, caused more episodes of neutropenia and hepatic complications. There was little difference between the rate of adverse events reported by those who were treated with 15 mg of upadacitinib and the placebo group. In conclusion, 45 mg of upadacitinib can be effectively used to manage Crohn’s disease, with the maintenance dose can be adjusted if needed. The researchers noted that a 5-year study is being conducted to investigate the long-term effects and if upadacitinib can lead to rare and long-latency adverse events.