ABSTRACT
Introduction: Guselkumab (GUS), an IL-23p19 antagonist, had greater efficacy than placebo (PBO) in achieving clinical response and clinical remission atWeek (Wk) 12 in the randomized, controlled Phase 2b QUASAR Induction Study 1 (NCT04033445) in patients with moderately to severely active ulcerative colitis (UC).1 Patients who were not in clinical response at Wk 12 received GUS treatment through Wk 24. Here, we report GUS cumulative efficacy and safety results for Induction Study 1. Method(s): Eligible patients had moderately to severely active UC (modified Mayo score of 5 to 9 with a Mayo endoscopy subscore >=2) at baseline. Patients were randomized 1:1:1 to IV GUS 200mg, 400mg, or PBO at Wks 0, 4, and 8. Patients who were not in clinical response to IV induction at Wk 12 received GUS treatment (PBO IV->GUS 200mg IV;GUS 200mg IV->GUS 200mg SC;GUS 400mg IV->GUS 200mg SC) at Wks 12, 16, and 20 and were evaluated at Wk 24 (Figure). Matching IV or SC PBO was administered to maintain the blind. Result(s): Three hundred thirteen patients were randomized and treated at baseline. Demographic and disease characteristics at baseline were similar among the treatment groups, and approximately 50% had a prior inadequate response or intolerance to advanced UC therapy. AtWk 12, clinical response was achieved by 61.4% (62/101) and 60.7% (65/107) of patients randomized to GUS 200mg and GUS 400mg IV vs 27.6 % (29/105) of patients randomized to PBO IV (both p< 0.001). Of the patients in the GUS groups who were not in clinical response at Wk 12, 54.3% (19/35) in the GUS 200mg IV->200mg SC group and 50.0% (19/38) in the GUS 400mg IV->200mg SC group achieved clinical response at Wk 24. Clinical response atWk 12 or 24 was achieved by 80.2% of patients who were randomized to GUS 200mg IV and 78.5% of patients who were randomized to GUS 400mg IV. For patients who received PBO IV->GUS 200mg IV, clinical response at Wk 24 (65.2%) was similar toWk 12 clinical response following GUS 200mg IV induction (61.4%). The most frequent adverse events among all GUS-treated pts (n=274) were anemia (7.7%), headache (5.1%), worsening UC (4.4%), COVID-19 (3.6%), arthralgia (2.9%) and abdominal pain (2.6%) which are consistent with Wk 12 results. Conclusion(s): Overall, approximately 80% of patients randomized to receive GUS achieved clinical response at Wk 12 or 24. Continued treatment with SC GUS allowed 50-54.3% of IV GUS Wk 12 clinical nonresponders to achieve clinical response at Wk 24. No new safety concerns for GUS were identified. (Figure Presented).
ABSTRACT
Background: Guselkumab (GUS), an IL-23p19 antagonist, had greater efficacy than placebo (PBO) in achieving clinical response and clinical remission at Week (Wk) 12 in the randomized, controlled Phase 2b QUASAR Induction Study 1 (NCT04033445) in patients with moderately to severely active ulcerative colitis (UC).1 Patients who were not in clinical response at Wk 12 received GUS treatment through Wk 24. Here, we report GUS cumulative efficacy and safety results for Induction Study 1. Method(s): Eligible patients had moderately to severely active UC (modified Mayo score of 5 to 9 with a Mayo endoscopy subscore >=2) at baseline. Patients were randomized 1:1:1 to IV GUS 200mg, 400mg, or PBO at Wks 0, 4, and 8. Patients who were not in clinical response to IV induction at Wk 12 received GUS treatment (PBO IVGUS 200mg IV;GUS 200mg IV->GUS 200mg SC;GUS 400mg IV->GUS 200mg SC) at Wks 12, 16, and 20 and were evaluated at Wk 24 (Figure 1). Matching IV or SC PBO was administered to maintain the blind. Result(s): Three hundred thirteen patients were randomized and treated at baseline. Demographic and disease characteristics at baseline were similar among the treatment groups, and approximately 50% had a prior inadequate response or intolerance to advanced UC therapy. At Wk 12, clinical response was achieved by 61.4% (62/101) and 60.7% (65/107) of patients randomized to GUS 200mg and GUS 400mg IV vs 27.6% (29/105) of patients randomized to PBO IV (both p<0.001). Of the patients in the GUS groups who were not in clinical response at Wk 12, 54.3% (19/35) in the GUS 200mg IV->200mg SC group and 50.0% (19/38) in the GUS 400mg IV->200mg SC group achieved clinical response at Wk 24. Clinical response at Wk 12 or 24 was achieved by 80.2% of patients who were randomized to GUS 200mg IV and 78.5% of patients who were randomized to GUS 400mg IV. For patients who received PBO IV->GUS 200mg IV, clinical response at Wk 24 (65.2%) was similar to Wk 12 clinical response following GUS 200mg IV induction (61.4%). The most frequent adverse events among all GUS-treated pts (n=274) were anemia (7.7%), headache (5.1%), worsening UC (4.4%), COVID-19 (3.6%), arthralgia (2.9%) and abdominal pain (2.6%) which are consistent with Wk 12 results. Conclusion(s): Overall, approximately 80% of patients randomized to receive GUS achieved clinical response at Wk 12 or 24. Continued treatment with SC GUS allowed 50-54.3% of IV GUS Wk 12 clinical nonresponders to achieve clinical response at Wk 24. No new safety concerns for GUS were identified.
ABSTRACT
Background Immune responses to the SARS-CoV-2 vaccination may be influenced by immunomodulatory drugs (IMDs). We investigated the immune responses and safety in fully vaccinated Japanese patients with IBD. Methods IBD patients and control subjects at 39 institutes were invited to participate in the study from March to October 2021. Blood sample collections to measure anti-SARS-CoV-2 spike IgG antibody titers were planned pre-1st vaccination, pre-2nd vaccination, and at 4 weeks, 3 months and 6 months post-2nd vaccination. Immune responses were compared between groups, considering baseline characteristics and IMD treatments. (UMIN000043545) The interim analyses presented here include mainly data from the 4-weeks post-2nd vaccination time-point. Results In total, 679 IBD patients and 203 controls were enrolled (Table 1). The IBD group received the BNT162b2 vaccine (86.2%) and the mRNA-1273 vaccine (12.5%), and the control group received the BNT162b2 vaccine (86.9%) and the mRNA-1273 vaccine (12.1%). Only 4 cases (0.7%) in the IBD group and 2 (1.0%) in the control group were infected with COVID-19. Adverse events of 2nd vaccination occurred in 48.4% of the IBD group and 35.1% of the control group. Comparison between administrated and non-administrated IBD patients for each IMD revealed an attenuated genomic mean titer (GMT [U/mL]) in those taking systemic steroids (18.85 vs 31.24), anti-TNF monotherapy (28.31 vs 42.99), anti-TNF therapy+ immunomodulator (IM) (12.86 vs 35.26), vedolizumab+IM (19.49 vs 30.39), ustekinumab+IM (20.44 vs 30.79), and tofacitinib (9.54 vs 32.08), but not in those taking oral 5-ASA (29.50 vs 32.40), or vedolizumab (41.85 vs 40.20) and ustekinumab (55.56 vs 39.26) monotherapies. Estimated least square means of the GMT by a multiple linear regression model are shown in Table 2. GMTs were significantly influenced by increasing age and allergy (51.2, 95%CI 42.1–62.3;p=0.0293), and tended to be influenced by COVID-19 infection (139.1, 41.0–472.2;p=0.0572). Sex, smoking, drinking, IBD, and adverse events of 2nd vaccination did not affect the GMT. The GMT was significantly higher for mRNA-1273 (90.3 [60.8–134.1]) than for BNT162b2 (39.6 [35.2–44.6], p= 0.0001). Systemic steroids (22.9 [13.9–37.7], p=0.0119), IM (24.2 [18.7–31.4], p<0.0001), anti-TNF agents (20.8 [15.3–28.3], p<0.0001), vedolizumab (25.2 [15.0–42.2], p=0.0409), ustekinumab (28.9 [18.5–45.0], p=0.0754), and tofacitinib (5.5 [2.8–10.9], p<0.0001), but not oral 5-ASA (39.1 [31.9–47.9], p=0.3225), attenuated GMTs at 4 weeks post-2nd vaccination (Table 2). Conclusion Aging and most IMD options attenuated immunogenicity in fully vaccinated IBD patients. Prioritization of a booster vaccination should be considered for IBD patients treated with IMDs.
ABSTRACT
Background: Inflammatory bowel disease (IBD) is a disease with repeated relapses and remissions, and it is considered that IBD patients had more than a little conflict between the threat of COVID-19 infection by visiting the doctor and the anxiety about their own disease by postponing the visit. We investigated the impact of the COVID-19 pandemic on the anxiety and behavioral changes of Japanese IBD patients. Methods: We collected questionnaires from 3032 IBD patients aged 16 years or older attending 31 facilities in Japan between March 2020 and June 2021. The primary endpoint was anxiety felt by IBD patients during the COVID-19 pandemic. Results: The median age was 44 years;43.3% of the participants were female. 60.6% of the participants was diagnosed with ulcerative colitis and 39.4% with Crohn’s disease (CD), and the median disease duration was 10 years. Regarding IBD medications, about 80% of the patients were taking 5-ASA, followed by thiopurine (31.4%), biological agents (47.4%), and less than 10% of the patients were taking steroids or budesonide. 37.7% of participants reported that they were in clinical remission, whereas 35.6% were in mild and 19.3% were in moderate activity. The questionnaires were collected throughout the middle of the second wave to the end of four waves of COVID19 in Japan. The mean VAS score is 5.1±2.5 during this pandemic, which indicated moderate anxiety. The most frequent causes of anxiety were the risk of SARS-CoV-2 infection by visiting hospital, the risk of infection by IBD itself, and the risk of infection by IBD medication. Factors associated with anxiety are women, housewives, time to visit hospital, transportation by train, use of immunosuppressive drugs, and nutritional therapy. The results of the questionnaire survey on medical visits showed that about 90% of the patients went to the hospital and received treatment as scheduled. During this pandemic, 97.5% of the patients continued oral medication and injections as physicians indicated. Most of participants felt the need for a family doctor and primarily sought guidance, and information regarding SARS-COV-2 from television or internet news. 35.6% of the patients were given information about prevention of SARS-COV-2 by their physicians. 42.6% of the patients received an explanation about the continuation of medication from their physicians. Conclusion: Japanese IBD patients had moderate disease-related anxiety. The percentage of patients with a behavioral change was small. Based on the content of anxiety obtained in this study, we should continue to proactively inform patients about infectious diseases such as SARS-COV2 and the accompanying accurate information related to IBD management, thereby relieving their anxiety. (Figure Presented)
ABSTRACT
Background: The spread of COVID-19 has had a major impact on the health of people worldwide. The clinical background and clinical course of Japanese inflammatory bowel disease (IBD) patients with COVID-19 remains unclear. Patients with IBD are often on immunosuppressive therapy, and there has been concern about the severity of COVID-19. We conducted the multicenter registry study of Japanese patients with inflammatory bowel disease with COVID-19. Methods: This study is an observational cohort of Japanese IBD patients diagnosed with COVID-19, and was registered in the UMIN Clinical Trials Registry (ID UMIN000040656). Data on age, gender, IBD (classification, treatment, and activity), COVID-19 symptoms and severity, and treatment of COVID-19 were analyzed. Results: From 72 facilities in Japan, one hundred eighty-seven patients were registered from June 2020 to October 2021 (Table1). The estimated incidence ratio of COVID19 in Japanese IBD patients was 0.61%. The median age (±SD) was 42.0±15.6, 4.8% of patients were obese with BMI >30, 7.0% were current smokers, and 31.0% had some complications. Of the patients enrolled, 104 had ulcerative colitis, 74 had Crohn's disease, 3 had IBD-Unclassified, and 6 had intestinal Behcet's disease. The majority of IBD patients with COVID-19 (73%) were in clinical remission. COVID-19 cases were most common in the 20-50 age group, but the COVID-19 severity rate according to WHO classification tended to be higher in the elderly than in middle-aged persons (Figure1). In Japan, the second SARS-CoV-2 vaccination rate jumped from 0% to 90% in just four months from May to September 2021 because the elderly received vaccination preferentially. Therefore, during the fifth wave of the epidemic (July-September 2021), infections among elderly IBD patients were particularly low compared with the younger. According to WHO classification regarding COVID-19 severity, 172 patients (92%) had non-severe, 12 (6%) were severe including serious conditions. Most IBD patients (UC and CD) with COVID-19 had no change in disease activity. A logistic regression analysis stepwise method revealed that older age, higher BMI, and steroid use were risk factors for COVID-19 severity. Six of eight patients who had COVID-19 after vaccination were receiving anti-TNF-alpha antibodies. Conclusion: The estimated incidence ratio of COVID19 in Japanese IBD patients was 0.61%. Age, BMI, and steroid use were associated with COVID-19 severity in Japanese IBD patients. (Table Presented) Table1. Case profile of the registered patients (Figure Presented) Figure1. The Age distribution of patients with COVID-19 and the COVID-19 severity rate
ABSTRACT
Background: Immune responses to the SARS-CoV-2 vaccination may be influenced by immunomodulatory drugs (IMDs). We investigated the immune responses and safety in fully vaccinated Japanese patients with IBD. Subjects and Methods: IBD patients and control subjects at 39 institutes were invited to participate in the study from March to October 2021. Blood sample collections to measure anti-SARS-CoV-2 spike IgG antibody titers were planned pre-1st vaccination, pre-2nd vaccination, and at 4 weeks, 3 months and 6 months post-2nd vaccination. Immune responses were compared between groups, considering baseline characteristics and IMD treatments. (UMIN000043545) The interim analyses presented here include mainly data from the 4-weeks post-2nd vaccination time-point. Results: In total, 679 IBD patients and 203 controls were enrolled (Table 1). The IBD group received the BNT162b2 vaccine (86.2%) and the mRNA-1273 vaccine (12.5%), and the control group received the BNT162b2 vaccine (86.9%) and the mRNA-1273 vaccine (12.1%). Only 4 cases (0.7%) in the IBD group and 2 (1.0%) in the control group were infected with COVID-19. Adverse events of 2nd vaccination occurred in 48.4% of the IBD group and 35.1% of the control group. Comparison between administrated and non-administrated IBD patients for each IMD revealed an attenuated genomic mean titer (GMT [U/mL]) in those taking systemic steroids (18.85 vs 31.24), anti-TNF monotherapy (28.31 vs 42.99), anti- TNF therapy+ immunomodulator (IM) (12.86 vs 35.26), vedolizumab+IM (19.49 vs 30.39), ustekinumab+IM (20.44 vs 30.79), and tofacitinib (9.54 vs 32.08), but not in those taking oral 5-ASA (29.50 vs 32.40), or vedolizumab (41.85 vs 40.20) and ustekinumab (55.56 vs 39.26) monotherapies. Estimated least square means of the GMT by a multiple linear regression model are shown in Table 2. GMTs were significantly influenced by increasing age and allergy (51.2, 95%CI 42.1-62.3;p=0.0293), and tended to be influenced by COVID- 19 infection (139.1, 41.0-472.2;p=0.0572). Sex, smoking, drinking, IBD, and adverse events of 2nd vaccination did not affect the GMT. The GMT was significantly higher for mRNA- 1273 (90.3 [60.8-134.1]) than for BNT162b2 (39.6 [35.2-44.6], p= 0.0001). Systemic steroids (22.9 [13.9-37.7], p=0.0119), IM (24.2 [18.7-31.4], p<0.0001), anti-TNF agents (20.8 [15.3-28.3], p<0.0001), vedolizumab (25.2 [15.0-42.2], p=0.0409), ustekinumab (28.9 [18.5-45.0], p=0.0754), and tofacitinib (5.5 [2.8-10.9], p<0.0001), but not oral 5- ASA (39.1 [31.9-47.9], p=0.3225), attenuated GMTs at 4 weeks post-2nd vaccination (Table 2). Conclusion: Aging and most IMD options attenuated immunogenicity in fully vaccinated IBD patients. Prioritization of a booster vaccination should be considered for IBD patients treated with IMDs. (Table Presented) (Table Presented)
ABSTRACT
Background: Immune responses to the SARS-CoV-2 vaccination may be influenced by immunomodulatory drugs (IMDs). We investigated the immune responses and safety in fully vaccinated Japanese patients with IBD. Methods: IBD patients and control subjects at 39 institutes were invited to participate in the study from March to October 2021. Blood sample collections to measure anti-SARS-CoV-2 spike IgG antibody titers were planned pre-1st vaccination, pre-2nd vaccination, and at 4 weeks, 3 months and 6 months post-2nd vaccination. Immune responses were compared between groups, considering baseline characteristics and IMD treatments. (UMIN000043545) The interim analyses presented here include mainly data from the 4-weeks post-2nd vaccination time-point. Results: In total, 679 IBD patients and 203 controls were enrolled (Table 1). The IBD group received the BNT162b2 vaccine (86.2%) and the mRNA-1273 vaccine (12.5%), and the control group received the BNT162b2 vaccine (86.9%) and the mRNA-1273 vaccine (12.1%). Only 4 cases (0.7%) in the IBD group and 2 (1.0%) in the control group were infected with COVID-19. Adverse events of 2nd vaccination occurred in 48.4% of the IBD group and 35.1% of the control group. Comparison between administrated and nonadministrated IBD patients for each IMD revealed an attenuated genomic mean titer (GMT [U/mL]) in those taking systemic steroids (18.85 vs 31.24), anti-TNF monotherapy (28.31 vs 42.99), anti-TNF therapy+ immunomodulator (IM) (12.86 vs 35.26), vedolizumab+IM (19.49 vs 30.39), ustekinumab+IM (20.44 vs 30.79), and tofacitinib (9.54 vs 32.08), but not in those taking oral 5-ASA (29.50 vs 32.40), or vedolizumab (41.85 vs 40.20) and ustekinumab (55.56 vs 39.26) monotherapies. Estimated least square means of the GMT by a multiple linear regression model are shown in Table 2. GMTs were significantly influenced by increasing age and allergy (51.2, 95%CI 42.1-62.3;p=0.0293), and tended to be influenced by COVID-19 infection (139.1, 41.0-472.2;p=0.0572). Sex, smoking, drinking, IBD, and adverse events of 2nd vaccination did not affect the GMT. The GMT was significantly higher for mRNA-1273 (90.3 [60.8-134.1]) than for BNT162b2 (39.6 [35.2-44.6], p= 0.0001). Systemic steroids (22.9 [13.9-37.7], p=0.0119), IM (24.2 [18.7-31.4], p<0.0001), anti-TNF agents (20.8 [15.3-28.3], p<0.0001), vedolizumab (25.2 [15.0-42.2], p=0.0409), ustekinumab (28.9 [18.5-45.0], p=0.0754), and tofacitinib (5.5 [2.8-10.9], p<0.0001), but not oral 5-ASA (39.1 [31.9-47.9], p=0.3225), attenuated GMTs at 4 weeks post-2nd vaccination (Table 2). Conclusion: Aging and most IMD options attenuated immunogenicity in fully vaccinated IBD patients. Prioritization of a booster vaccination should be considered for IBD patients treated with IMDs.