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Introduction Crohn's disease (CD) is a chronic, progressive inflammatory disease that usually requires long-term treatment to control disease activity.
Many current maintenance treatments for CD have great limitations, including insufficient efficacy and adverse events.
In recent years, with further research on the pathogenesis of CD, it has been discovered that a variety of new biological agents can be used in the treatment of CD.
Ustekinumab is an IgG1 monoclonal antibody that targets the p40 subunit of IL-12/IL-23 and inhibits IL-12/IL-23 and T cells, NK cells and antigen presenting cells Surface receptors bind to reduce inflammation.
Approved in 2016 for the treatment of moderate to severe CD.
The subcutaneous injection (SC) maintenance therapy study (IM-UNITI) and the long-term extension (LTE) study are designed to evaluate the long-term efficacy, safety and immunogenicity of SC ussnumab maintenance therapy in patients with CD.
This article reports the final results of IM-UNITI and LTE research after 5 years.
Study Introduction The research projects of Uselumumab in the treatment of CD include 2 randomized double-blind, placebo-controlled, 8-week, intravenous (IV) induction therapy studies (UNITI-1/UNITI-2), and 1 IM for 44 weeks -UNITI and 1 LTE study lasting 272 weeks.
1.
Patients who responded to the IV induction therapy with Uselnumumab were randomized to receive SC placebo or Uselnumumab (90 mg q8w or q12w) maintenance treatment.
2.
Patients who initially did not respond to Uselnumab or placebo IV induction, received a single dose of Uselnumab SC or IV at the 8th week after induction (IM-UNITI week 0).If these patients respond after 8 weeks, as a non-randomized population, continue to receive SC usnumab (90 mg q8w or q12w, respectively) as maintenance therapy.
3.
Patients who responded to placebo IV induction therapy were also included in the non-randomized population and continued to receive placebo maintenance treatment.
4.
Patients who have completed the safety and efficacy assessment in the 44th week of maintenance treatment and the investigator believes that they may benefit from continued treatment are eligible to participate in the LTE study and continue to receive the treatment they are receiving.
5.
After completing the analysis of the maintenance treatment study (August 2015), at this time, patients still receiving SC placebo discontinue the study, and patients receiving ulinumumab continue to receive the current dose in an open manner .
The dose was not adjusted during LTE.
6.
During LTE, the efficacy evaluation will be conducted once every 12 weeks until the blind is unblinded, and then the efficacy evaluation will be conducted during the dosing visit until the 252th week.
Serum ulinumumab concentration and anti-drug antibody (ADA) were assessed at 252 and 272 weeks, respectively.
The results of the study were 397 patients who responded after 8 weeks of induction therapy with usinumumab and were randomized to receive placebo, usinumumab 90 mg q12w or usinumumab 90 mg q8w SC maintenance treatment.
After reaching the primary endpoint of IM-UNITI Week 44, 298 randomized patients joined the LTE study.
1.
Long-term efficacy The intention-to-treat analysis of all patients who were randomized to receive ulinumumab treatment at the baseline of the maintenance treatment study showed that the proportions of patients in the q8w group and q12w group who achieved clinical remission at week 252 were 34.
4% and 28.
7%, respectively .
Among them, the clinical remission rates of patients who joined the LTE study at week 252 were 54.
9% and 45.
2%, respectively. 2.
Safety Generally speaking, from the 0th week of maintenance treatment to the last visit, all adverse events (440.
3 vs.
327.
6) and serious adverse events (19.
3 vs.
17.
5) in the placebo group and uzumumab combined treatment group The incidence (per 100 patient-years) of infection (99.
8 vs.
93.
8) and severe infection (3.
9 vs.
3.
4) are basically similar.
3.
Immunogenicity Throughout the LTE period, the serum ulinumumab concentration remained unchanged.
ADA occurred in 5.
8% of patients who received induction and maintenance therapy with usnumab and continued to receive treatment during LTE.
Conclusion Patients receiving SC usnisumab can maintain clinical remission within 5 years.
No new safety signals have been observed so far.
References: [1] Sandborn WJ, Rebuck R, Wang Y, et al.
Five-year Efficacy and Safety of Ustekinumab Treatment in Crohn's Disease: the IM-UNITI trial[J].
Clin Gastroenterol Hepatol.
2021 Feb 19;S1542- 3565(21)00203-2.
[2] Zheng Yadan, Li Ling, Pang Zhi.
The latest research progress in biotherapy of inflammatory bowel disease[J].
Journal of Gastroenterology and Hepatology, 2020, 29(02):212 -218.
Many current maintenance treatments for CD have great limitations, including insufficient efficacy and adverse events.
In recent years, with further research on the pathogenesis of CD, it has been discovered that a variety of new biological agents can be used in the treatment of CD.
Ustekinumab is an IgG1 monoclonal antibody that targets the p40 subunit of IL-12/IL-23 and inhibits IL-12/IL-23 and T cells, NK cells and antigen presenting cells Surface receptors bind to reduce inflammation.
Approved in 2016 for the treatment of moderate to severe CD.
The subcutaneous injection (SC) maintenance therapy study (IM-UNITI) and the long-term extension (LTE) study are designed to evaluate the long-term efficacy, safety and immunogenicity of SC ussnumab maintenance therapy in patients with CD.
This article reports the final results of IM-UNITI and LTE research after 5 years.
Study Introduction The research projects of Uselumumab in the treatment of CD include 2 randomized double-blind, placebo-controlled, 8-week, intravenous (IV) induction therapy studies (UNITI-1/UNITI-2), and 1 IM for 44 weeks -UNITI and 1 LTE study lasting 272 weeks.
1.
Patients who responded to the IV induction therapy with Uselnumumab were randomized to receive SC placebo or Uselnumumab (90 mg q8w or q12w) maintenance treatment.
2.
Patients who initially did not respond to Uselnumab or placebo IV induction, received a single dose of Uselnumab SC or IV at the 8th week after induction (IM-UNITI week 0).If these patients respond after 8 weeks, as a non-randomized population, continue to receive SC usnumab (90 mg q8w or q12w, respectively) as maintenance therapy.
3.
Patients who responded to placebo IV induction therapy were also included in the non-randomized population and continued to receive placebo maintenance treatment.
4.
Patients who have completed the safety and efficacy assessment in the 44th week of maintenance treatment and the investigator believes that they may benefit from continued treatment are eligible to participate in the LTE study and continue to receive the treatment they are receiving.
5.
After completing the analysis of the maintenance treatment study (August 2015), at this time, patients still receiving SC placebo discontinue the study, and patients receiving ulinumumab continue to receive the current dose in an open manner .
The dose was not adjusted during LTE.
6.
During LTE, the efficacy evaluation will be conducted once every 12 weeks until the blind is unblinded, and then the efficacy evaluation will be conducted during the dosing visit until the 252th week.
Serum ulinumumab concentration and anti-drug antibody (ADA) were assessed at 252 and 272 weeks, respectively.
The results of the study were 397 patients who responded after 8 weeks of induction therapy with usinumumab and were randomized to receive placebo, usinumumab 90 mg q12w or usinumumab 90 mg q8w SC maintenance treatment.
After reaching the primary endpoint of IM-UNITI Week 44, 298 randomized patients joined the LTE study.
1.
Long-term efficacy The intention-to-treat analysis of all patients who were randomized to receive ulinumumab treatment at the baseline of the maintenance treatment study showed that the proportions of patients in the q8w group and q12w group who achieved clinical remission at week 252 were 34.
4% and 28.
7%, respectively .
Among them, the clinical remission rates of patients who joined the LTE study at week 252 were 54.
9% and 45.
2%, respectively. 2.
Safety Generally speaking, from the 0th week of maintenance treatment to the last visit, all adverse events (440.
3 vs.
327.
6) and serious adverse events (19.
3 vs.
17.
5) in the placebo group and uzumumab combined treatment group The incidence (per 100 patient-years) of infection (99.
8 vs.
93.
8) and severe infection (3.
9 vs.
3.
4) are basically similar.
3.
Immunogenicity Throughout the LTE period, the serum ulinumumab concentration remained unchanged.
ADA occurred in 5.
8% of patients who received induction and maintenance therapy with usnumab and continued to receive treatment during LTE.
Conclusion Patients receiving SC usnisumab can maintain clinical remission within 5 years.
No new safety signals have been observed so far.
References: [1] Sandborn WJ, Rebuck R, Wang Y, et al.
Five-year Efficacy and Safety of Ustekinumab Treatment in Crohn's Disease: the IM-UNITI trial[J].
Clin Gastroenterol Hepatol.
2021 Feb 19;S1542- 3565(21)00203-2.
[2] Zheng Yadan, Li Ling, Pang Zhi.
The latest research progress in biotherapy of inflammatory bowel disease[J].
Journal of Gastroenterology and Hepatology, 2020, 29(02):212 -218.
