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Janus kinase inhibitors (JAK inhibitors) have demonstrated efficacy in several immune mediated inflammatory conditions. Tofacitinib, which inhibits JAK3 and JAK1 greater than JAK2, was the first JAK inhibitor approved by the FDA for ulcerative colitis. In contrast to tofacitinib, filgotinib, preferentially inhibits JAK1. The efficacy of filgotinib during induction and maintenance therapy in ulcerative colitis was studied in a phase 2b/3 randomized control trial, the SELECTION trial. In this trial, 659 biologic-naïve and 689 biologic-experienced patients with moderate to severely active ulcerative colitis were randomized 2:2:1 to receive filgotinib 200mg daily, filgotinib 100mg daily, or placebo for 11 weeks. Responders to treatment with filgotinib at week 10 were rerandomized to their original dose or placebo in a 2:1 manner for a total treatment course of 58 weeks. The primary endpoint of the study was clinical remission which was defined as a Mayo endoscopy subscore of 0 or 1, rectal bleeding subscore of 0, and at least a 1-point decrease in stool frequency from baseline for a subscore of 0 or 1.
In biologic naïve patients, 26.1% of patients treated with filgotinib 200mg (P = .016) and 19.1% treated with filgotinib 100mg (P = 0.34) compared to 15.3% in the placebo groups achieved clinical remission at week 10. In patients previously treated with an anti-TNF agent or vedolizumab, 4.2% of patients receiving placebo compared to 11.5% taking filgotinib 200mg (P = 0.01) and 9.5% taking filgotinib 100 mg (P = .065) achieved clinical remission at week 10. Endoscopic remission was observed after induction therapy in 12.2% of patients receiving filgotinib 200 mg compared with 3.6% placebo in biologic naïve patients (P = .0047) and 3.4% of patients receiving filgotinib 200 mg compared to 2.1% of patients receiving placebo in biologic experienced patients (P = .43). Histologic remission was achieved in both biologic-naïve and biologic-experienced patients at the 200 mg dose significantly more frequently than in patients receiving placebo. At week 58, 37.2% of patients receiving filgotinib 200 mg and 11.2% of patients receiving placebo (P < .0001) were in clinical remission. In addition, 23.8% of patients receiving 100 mg were in clinical remission compared to 13.2% of patients in the placebo arm (P = .04). These results support that filgotinib may be another effective option for treating patients with moderate to severe ulcerative colitis.
Biosimilars to infliximab are increasingly used in clinical practice. Previous studies have demonstrated safety and efficacy of a single switch from originator to biosimilar infliximab. There is limited data, however, on performing multiple successive switches. In a multicenter prospective cohort, Hanzel et al evaluated 176 patients with inflammatory bowel disease (IBD). The investigators compared outcomes in three groups: group 1 (infliximab originator [INX] to CT-P13 to SB2; 2 switches), group 2 (CT-P13 to SB2; 1 switch) and group 3 (INX to CT-P13; 1 switch). After 12 months, there were no differences in the rates of clinical remission, treatment persistence, or fecal calprotectin. There were 3 infusion reactions in patients switched from CT-P13 to SB2 and none in the other 2 groups. In conclusion, 2 switches of biosimilars in this prospective cohort were not associated with a change in effectiveness or safety.
The effectiveness of SARS-CoV2 vaccinations in an IBD population is not well known. In a retrospective cohort study with a median age of 68 years including 7376 unvaccinated and 7321 vaccinated veterans, Khan and Mahmud demonstrated the efficacy of full vaccination with the Pfizer or Moderna vaccine in preventing infection, severe infection, and death. In this cohort, less than half of patients were on a biologic or immunomodulator. Of the 6253 patients who were fully vaccinated, there were 7 infections and 3 serious infections compared to 197 infections, 47 serious infections, and 97 deaths in the 14,697 individuals monitored during an unvaccinated time period. Full vaccination (compared to unvaccinated) was 80.4% effective at preventing infection, 70.1% at preventing serious infection, and 87.3% effective and preventing all-cause mortality, whereas partial vaccination was 25.1% effective at preventing infection, 36.8% at preventing severe infection, and 27.3% at preventing all-cause mortality.
This study demonstrates the efficacy of full vaccination in patients with IBD with limited protection for patients receiving partial vaccination. It is limited by the fact that many patients considered unvaccinated may have been vaccinated outside the VA system, the relatively few numbers of events in vaccinated individuals, and lack of generalizability to other settings of patients with IBD as this study involved older men with relatively low rates of immunosuppression.
Janus kinase inhibitors (JAK inhibitors) have demonstrated efficacy in several immune mediated inflammatory conditions. Tofacitinib, which inhibits JAK3 and JAK1 greater than JAK2, was the first JAK inhibitor approved by the FDA for ulcerative colitis. In contrast to tofacitinib, filgotinib, preferentially inhibits JAK1. The efficacy of filgotinib during induction and maintenance therapy in ulcerative colitis was studied in a phase 2b/3 randomized control trial, the SELECTION trial. In this trial, 659 biologic-naïve and 689 biologic-experienced patients with moderate to severely active ulcerative colitis were randomized 2:2:1 to receive filgotinib 200mg daily, filgotinib 100mg daily, or placebo for 11 weeks. Responders to treatment with filgotinib at week 10 were rerandomized to their original dose or placebo in a 2:1 manner for a total treatment course of 58 weeks. The primary endpoint of the study was clinical remission which was defined as a Mayo endoscopy subscore of 0 or 1, rectal bleeding subscore of 0, and at least a 1-point decrease in stool frequency from baseline for a subscore of 0 or 1.
In biologic naïve patients, 26.1% of patients treated with filgotinib 200mg (P = .016) and 19.1% treated with filgotinib 100mg (P = 0.34) compared to 15.3% in the placebo groups achieved clinical remission at week 10. In patients previously treated with an anti-TNF agent or vedolizumab, 4.2% of patients receiving placebo compared to 11.5% taking filgotinib 200mg (P = 0.01) and 9.5% taking filgotinib 100 mg (P = .065) achieved clinical remission at week 10. Endoscopic remission was observed after induction therapy in 12.2% of patients receiving filgotinib 200 mg compared with 3.6% placebo in biologic naïve patients (P = .0047) and 3.4% of patients receiving filgotinib 200 mg compared to 2.1% of patients receiving placebo in biologic experienced patients (P = .43). Histologic remission was achieved in both biologic-naïve and biologic-experienced patients at the 200 mg dose significantly more frequently than in patients receiving placebo. At week 58, 37.2% of patients receiving filgotinib 200 mg and 11.2% of patients receiving placebo (P < .0001) were in clinical remission. In addition, 23.8% of patients receiving 100 mg were in clinical remission compared to 13.2% of patients in the placebo arm (P = .04). These results support that filgotinib may be another effective option for treating patients with moderate to severe ulcerative colitis.
Biosimilars to infliximab are increasingly used in clinical practice. Previous studies have demonstrated safety and efficacy of a single switch from originator to biosimilar infliximab. There is limited data, however, on performing multiple successive switches. In a multicenter prospective cohort, Hanzel et al evaluated 176 patients with inflammatory bowel disease (IBD). The investigators compared outcomes in three groups: group 1 (infliximab originator [INX] to CT-P13 to SB2; 2 switches), group 2 (CT-P13 to SB2; 1 switch) and group 3 (INX to CT-P13; 1 switch). After 12 months, there were no differences in the rates of clinical remission, treatment persistence, or fecal calprotectin. There were 3 infusion reactions in patients switched from CT-P13 to SB2 and none in the other 2 groups. In conclusion, 2 switches of biosimilars in this prospective cohort were not associated with a change in effectiveness or safety.
The effectiveness of SARS-CoV2 vaccinations in an IBD population is not well known. In a retrospective cohort study with a median age of 68 years including 7376 unvaccinated and 7321 vaccinated veterans, Khan and Mahmud demonstrated the efficacy of full vaccination with the Pfizer or Moderna vaccine in preventing infection, severe infection, and death. In this cohort, less than half of patients were on a biologic or immunomodulator. Of the 6253 patients who were fully vaccinated, there were 7 infections and 3 serious infections compared to 197 infections, 47 serious infections, and 97 deaths in the 14,697 individuals monitored during an unvaccinated time period. Full vaccination (compared to unvaccinated) was 80.4% effective at preventing infection, 70.1% at preventing serious infection, and 87.3% effective and preventing all-cause mortality, whereas partial vaccination was 25.1% effective at preventing infection, 36.8% at preventing severe infection, and 27.3% at preventing all-cause mortality.
This study demonstrates the efficacy of full vaccination in patients with IBD with limited protection for patients receiving partial vaccination. It is limited by the fact that many patients considered unvaccinated may have been vaccinated outside the VA system, the relatively few numbers of events in vaccinated individuals, and lack of generalizability to other settings of patients with IBD as this study involved older men with relatively low rates of immunosuppression.
Janus kinase inhibitors (JAK inhibitors) have demonstrated efficacy in several immune mediated inflammatory conditions. Tofacitinib, which inhibits JAK3 and JAK1 greater than JAK2, was the first JAK inhibitor approved by the FDA for ulcerative colitis. In contrast to tofacitinib, filgotinib, preferentially inhibits JAK1. The efficacy of filgotinib during induction and maintenance therapy in ulcerative colitis was studied in a phase 2b/3 randomized control trial, the SELECTION trial. In this trial, 659 biologic-naïve and 689 biologic-experienced patients with moderate to severely active ulcerative colitis were randomized 2:2:1 to receive filgotinib 200mg daily, filgotinib 100mg daily, or placebo for 11 weeks. Responders to treatment with filgotinib at week 10 were rerandomized to their original dose or placebo in a 2:1 manner for a total treatment course of 58 weeks. The primary endpoint of the study was clinical remission which was defined as a Mayo endoscopy subscore of 0 or 1, rectal bleeding subscore of 0, and at least a 1-point decrease in stool frequency from baseline for a subscore of 0 or 1.
In biologic naïve patients, 26.1% of patients treated with filgotinib 200mg (P = .016) and 19.1% treated with filgotinib 100mg (P = 0.34) compared to 15.3% in the placebo groups achieved clinical remission at week 10. In patients previously treated with an anti-TNF agent or vedolizumab, 4.2% of patients receiving placebo compared to 11.5% taking filgotinib 200mg (P = 0.01) and 9.5% taking filgotinib 100 mg (P = .065) achieved clinical remission at week 10. Endoscopic remission was observed after induction therapy in 12.2% of patients receiving filgotinib 200 mg compared with 3.6% placebo in biologic naïve patients (P = .0047) and 3.4% of patients receiving filgotinib 200 mg compared to 2.1% of patients receiving placebo in biologic experienced patients (P = .43). Histologic remission was achieved in both biologic-naïve and biologic-experienced patients at the 200 mg dose significantly more frequently than in patients receiving placebo. At week 58, 37.2% of patients receiving filgotinib 200 mg and 11.2% of patients receiving placebo (P < .0001) were in clinical remission. In addition, 23.8% of patients receiving 100 mg were in clinical remission compared to 13.2% of patients in the placebo arm (P = .04). These results support that filgotinib may be another effective option for treating patients with moderate to severe ulcerative colitis.
Biosimilars to infliximab are increasingly used in clinical practice. Previous studies have demonstrated safety and efficacy of a single switch from originator to biosimilar infliximab. There is limited data, however, on performing multiple successive switches. In a multicenter prospective cohort, Hanzel et al evaluated 176 patients with inflammatory bowel disease (IBD). The investigators compared outcomes in three groups: group 1 (infliximab originator [INX] to CT-P13 to SB2; 2 switches), group 2 (CT-P13 to SB2; 1 switch) and group 3 (INX to CT-P13; 1 switch). After 12 months, there were no differences in the rates of clinical remission, treatment persistence, or fecal calprotectin. There were 3 infusion reactions in patients switched from CT-P13 to SB2 and none in the other 2 groups. In conclusion, 2 switches of biosimilars in this prospective cohort were not associated with a change in effectiveness or safety.
The effectiveness of SARS-CoV2 vaccinations in an IBD population is not well known. In a retrospective cohort study with a median age of 68 years including 7376 unvaccinated and 7321 vaccinated veterans, Khan and Mahmud demonstrated the efficacy of full vaccination with the Pfizer or Moderna vaccine in preventing infection, severe infection, and death. In this cohort, less than half of patients were on a biologic or immunomodulator. Of the 6253 patients who were fully vaccinated, there were 7 infections and 3 serious infections compared to 197 infections, 47 serious infections, and 97 deaths in the 14,697 individuals monitored during an unvaccinated time period. Full vaccination (compared to unvaccinated) was 80.4% effective at preventing infection, 70.1% at preventing serious infection, and 87.3% effective and preventing all-cause mortality, whereas partial vaccination was 25.1% effective at preventing infection, 36.8% at preventing severe infection, and 27.3% at preventing all-cause mortality.
This study demonstrates the efficacy of full vaccination in patients with IBD with limited protection for patients receiving partial vaccination. It is limited by the fact that many patients considered unvaccinated may have been vaccinated outside the VA system, the relatively few numbers of events in vaccinated individuals, and lack of generalizability to other settings of patients with IBD as this study involved older men with relatively low rates of immunosuppression.