IBD & Intestinal Disorders

Key clinical point: Hyperbaric oxygen therapy (HBOT) was safe and associated with substantial rates of clinical remission in patients with various inflammatory bowel disease (IBD) phenotypes refractory to conventional therapies.

Major finding: HBOT resulted in substantial rates of clinical remission across multiple IBD phenotypes including ulcerative colitis (67%; 95% confidence interval [CI], 39%-86%), luminal Crohn’s disease (CD; 87.5%; 95% CI, 46.3%-98.3%), perianal CD (55%; 95% CI, 44%-65%), inflammatory disorders of the pouch (31%; 95% CI, 16%-50%), pyoderma gangrenosum (91.7%; 95% CI, 37.8%-99.5%), and perianal sinus/metastatic CD (65.2%; 95% CI, 10%-96.9%). Overall, 15% of patients reported minor adverse events.

Study details: Data come from a systematic review and proportional meta-analysis of 19 studies.

Disclosures: No information on funding was available. Some of the authors disclosed receiving consultancy fees and/or honoraria from multiple sources. All other authors had no conflicts of interest to disclose.

Source: McCurdy J et al. Inflamm Bowel Dis. 2021 May 18. doi: 10.1093/ibd/izab098.

Key clinical point: Hyperbaric oxygen therapy (HBOT) was safe and associated with substantial rates of clinical remission in patients with various inflammatory bowel disease (IBD) phenotypes refractory to conventional therapies.

Major finding: HBOT resulted in substantial rates of clinical remission across multiple IBD phenotypes including ulcerative colitis (67%; 95% confidence interval [CI], 39%-86%), luminal Crohn’s disease (CD; 87.5%; 95% CI, 46.3%-98.3%), perianal CD (55%; 95% CI, 44%-65%), inflammatory disorders of the pouch (31%; 95% CI, 16%-50%), pyoderma gangrenosum (91.7%; 95% CI, 37.8%-99.5%), and perianal sinus/metastatic CD (65.2%; 95% CI, 10%-96.9%). Overall, 15% of patients reported minor adverse events.

Study details: Data come from a systematic review and proportional meta-analysis of 19 studies.

Disclosures: No information on funding was available. Some of the authors disclosed receiving consultancy fees and/or honoraria from multiple sources. All other authors had no conflicts of interest to disclose.

Source: McCurdy J et al. Inflamm Bowel Dis. 2021 May 18. doi: 10.1093/ibd/izab098.

Key clinical point: Hyperbaric oxygen therapy (HBOT) was safe and associated with substantial rates of clinical remission in patients with various inflammatory bowel disease (IBD) phenotypes refractory to conventional therapies.

Major finding: HBOT resulted in substantial rates of clinical remission across multiple IBD phenotypes including ulcerative colitis (67%; 95% confidence interval [CI], 39%-86%), luminal Crohn’s disease (CD; 87.5%; 95% CI, 46.3%-98.3%), perianal CD (55%; 95% CI, 44%-65%), inflammatory disorders of the pouch (31%; 95% CI, 16%-50%), pyoderma gangrenosum (91.7%; 95% CI, 37.8%-99.5%), and perianal sinus/metastatic CD (65.2%; 95% CI, 10%-96.9%). Overall, 15% of patients reported minor adverse events.

Study details: Data come from a systematic review and proportional meta-analysis of 19 studies.

Disclosures: No information on funding was available. Some of the authors disclosed receiving consultancy fees and/or honoraria from multiple sources. All other authors had no conflicts of interest to disclose.

Source: McCurdy J et al. Inflamm Bowel Dis. 2021 May 18. doi: 10.1093/ibd/izab098.

Key clinical point: In patients with inflammatory bowel disease (IBD), multiple successive switching from originator infliximab (IFX) to biosimilars (CT-P13 and SB2) was effective and safe, particularly if patients were in remission during the switch.

Major finding: At 12 months after the most recent switch, 76.9%, 65.7%, and 76.9% of patients successively switching from IFX to CT-P13 and then to SB2, from CT-P13 to SB2, and from IFX to CT-P13, respectively, were in clinical remission. Rate of clinical remission (P = .375), C-reactive protein (P = .582), and fecal calprotectin remission (P = .641) was not significantly different between the 3 groups. Overall, infusion reactions occurred in 1.7% of patients.

Study details: Data come from a multicenter prospective cohort study of 176 patients with IBD who switched from originator IFX to CT-P13 and then to SB2 (n=69), from CT-P13 to SB2 (n=80), or from IFX to CT-P13 (n=27).

Disclosures: No information on funding was available. Some of the authors reported serving on advisory boards or as a speaker or consultant for and receiving speaker’s fees, consultancy fees, and/or honoraria from multiple sources.

Source: Hanzel J et al. Inflamm Bowel Dis. 2021 May 20. doi: 10.1093/ibd/izab099.

Key clinical point: In patients with inflammatory bowel disease (IBD), multiple successive switching from originator infliximab (IFX) to biosimilars (CT-P13 and SB2) was effective and safe, particularly if patients were in remission during the switch.

Major finding: At 12 months after the most recent switch, 76.9%, 65.7%, and 76.9% of patients successively switching from IFX to CT-P13 and then to SB2, from CT-P13 to SB2, and from IFX to CT-P13, respectively, were in clinical remission. Rate of clinical remission (P = .375), C-reactive protein (P = .582), and fecal calprotectin remission (P = .641) was not significantly different between the 3 groups. Overall, infusion reactions occurred in 1.7% of patients.

Study details: Data come from a multicenter prospective cohort study of 176 patients with IBD who switched from originator IFX to CT-P13 and then to SB2 (n=69), from CT-P13 to SB2 (n=80), or from IFX to CT-P13 (n=27).

Disclosures: No information on funding was available. Some of the authors reported serving on advisory boards or as a speaker or consultant for and receiving speaker’s fees, consultancy fees, and/or honoraria from multiple sources.

Source: Hanzel J et al. Inflamm Bowel Dis. 2021 May 20. doi: 10.1093/ibd/izab099.

Key clinical point: In patients with inflammatory bowel disease (IBD), multiple successive switching from originator infliximab (IFX) to biosimilars (CT-P13 and SB2) was effective and safe, particularly if patients were in remission during the switch.

Major finding: At 12 months after the most recent switch, 76.9%, 65.7%, and 76.9% of patients successively switching from IFX to CT-P13 and then to SB2, from CT-P13 to SB2, and from IFX to CT-P13, respectively, were in clinical remission. Rate of clinical remission (P = .375), C-reactive protein (P = .582), and fecal calprotectin remission (P = .641) was not significantly different between the 3 groups. Overall, infusion reactions occurred in 1.7% of patients.

Study details: Data come from a multicenter prospective cohort study of 176 patients with IBD who switched from originator IFX to CT-P13 and then to SB2 (n=69), from CT-P13 to SB2 (n=80), or from IFX to CT-P13 (n=27).

Disclosures: No information on funding was available. Some of the authors reported serving on advisory boards or as a speaker or consultant for and receiving speaker’s fees, consultancy fees, and/or honoraria from multiple sources.

Source: Hanzel J et al. Inflamm Bowel Dis. 2021 May 20. doi: 10.1093/ibd/izab099.

Key clinical point: High-dose (HD) adalimumab maintenance regimen was associated with lower risk for treatment failure than standard dose (SD) regimen in patients with Crohn’s disease (CD) who failed antitumor necrosis factor (anti-TNF) therapy.

Major finding: The median time to treatment failure was 6.6 years vs. 3.0 years in the HD vs. SD group (log-rank test P = .006). The risk for treatment failure was lower in the HD vs. SD group (hazard ratio, 0.27; P = .002).

Study details: Findings are from a retrospective study of 117 patients with CD who failed anti-TNF and received adalimumab. Post induction, patients received either HD (40 mg weekly or 80 mg every other week; n=40) or SD (40 mg every other week; n=77) adalimumab maintenance regimen.

Disclosures: No information on funding was available. Some of the authors reported receiving honoraria, research grants/support, and/or consulting fees from various sources.

Source: Narula N et al. J Gastroenterol Hepatol. 2021 May 21. doi: 10.1111/jgh.15551.

Key clinical point: High-dose (HD) adalimumab maintenance regimen was associated with lower risk for treatment failure than standard dose (SD) regimen in patients with Crohn’s disease (CD) who failed antitumor necrosis factor (anti-TNF) therapy.

Major finding: The median time to treatment failure was 6.6 years vs. 3.0 years in the HD vs. SD group (log-rank test P = .006). The risk for treatment failure was lower in the HD vs. SD group (hazard ratio, 0.27; P = .002).

Study details: Findings are from a retrospective study of 117 patients with CD who failed anti-TNF and received adalimumab. Post induction, patients received either HD (40 mg weekly or 80 mg every other week; n=40) or SD (40 mg every other week; n=77) adalimumab maintenance regimen.

Disclosures: No information on funding was available. Some of the authors reported receiving honoraria, research grants/support, and/or consulting fees from various sources.

Source: Narula N et al. J Gastroenterol Hepatol. 2021 May 21. doi: 10.1111/jgh.15551.

Key clinical point: High-dose (HD) adalimumab maintenance regimen was associated with lower risk for treatment failure than standard dose (SD) regimen in patients with Crohn’s disease (CD) who failed antitumor necrosis factor (anti-TNF) therapy.

Major finding: The median time to treatment failure was 6.6 years vs. 3.0 years in the HD vs. SD group (log-rank test P = .006). The risk for treatment failure was lower in the HD vs. SD group (hazard ratio, 0.27; P = .002).

Study details: Findings are from a retrospective study of 117 patients with CD who failed anti-TNF and received adalimumab. Post induction, patients received either HD (40 mg weekly or 80 mg every other week; n=40) or SD (40 mg every other week; n=77) adalimumab maintenance regimen.

Disclosures: No information on funding was available. Some of the authors reported receiving honoraria, research grants/support, and/or consulting fees from various sources.

Source: Narula N et al. J Gastroenterol Hepatol. 2021 May 21. doi: 10.1111/jgh.15551.

Key clinical point: Tofacitinib induced rapid clinical response with sustained efficacy in nearly half of the pediatric and young adults with medically refractory inflammatory bowel disease (IBD) with a safety profile similar to that in adults.

Major finding: By the end of 12-week induction period, 81% of patients remained on tofacitinib therapy with 42.9% showing clinical response and 33.3% in steroid-free remission. By 52 weeks, 58.8% remained on tofacitinib and 41.2% showed clinical response and were in steroid-free remission. There were 11 serious adverse events requiring hospitalization including 1 instance of sterile intra-abdominal abscess. Instances of thrombi, zoster reactivation, or clinically significant hyperlipidemia were not observed.

Study details: Findings are from a retrospective chart review of 21 patients aged 21 years or younger who were initiated on tofacitinib after failing at least 1 previous biologic therapy.

Disclosures: The authors do not disclose funding source.

Source: Moore H et al. J Pediatr Gastroenterol Nutr. 2021 Jun 1. doi: 10.1097/MPG.0000000000003190.

Key clinical point: Tofacitinib induced rapid clinical response with sustained efficacy in nearly half of the pediatric and young adults with medically refractory inflammatory bowel disease (IBD) with a safety profile similar to that in adults.

Major finding: By the end of 12-week induction period, 81% of patients remained on tofacitinib therapy with 42.9% showing clinical response and 33.3% in steroid-free remission. By 52 weeks, 58.8% remained on tofacitinib and 41.2% showed clinical response and were in steroid-free remission. There were 11 serious adverse events requiring hospitalization including 1 instance of sterile intra-abdominal abscess. Instances of thrombi, zoster reactivation, or clinically significant hyperlipidemia were not observed.

Study details: Findings are from a retrospective chart review of 21 patients aged 21 years or younger who were initiated on tofacitinib after failing at least 1 previous biologic therapy.

Disclosures: The authors do not disclose funding source.

Source: Moore H et al. J Pediatr Gastroenterol Nutr. 2021 Jun 1. doi: 10.1097/MPG.0000000000003190.

Key clinical point: Tofacitinib induced rapid clinical response with sustained efficacy in nearly half of the pediatric and young adults with medically refractory inflammatory bowel disease (IBD) with a safety profile similar to that in adults.

Major finding: By the end of 12-week induction period, 81% of patients remained on tofacitinib therapy with 42.9% showing clinical response and 33.3% in steroid-free remission. By 52 weeks, 58.8% remained on tofacitinib and 41.2% showed clinical response and were in steroid-free remission. There were 11 serious adverse events requiring hospitalization including 1 instance of sterile intra-abdominal abscess. Instances of thrombi, zoster reactivation, or clinically significant hyperlipidemia were not observed.

Study details: Findings are from a retrospective chart review of 21 patients aged 21 years or younger who were initiated on tofacitinib after failing at least 1 previous biologic therapy.

Disclosures: The authors do not disclose funding source.

Source: Moore H et al. J Pediatr Gastroenterol Nutr. 2021 Jun 1. doi: 10.1097/MPG.0000000000003190.

Key clinical point: Prior immunogenicity to anti-tumor necrosis factor (TNF) agents did not confer an increased risk for subsequent immunogenicity to ustekinumab (UST) or vedolizumab (VED) in patients with inflammatory bowel disease (IBD).

Major finding: The rates of anti-drug antibody (ADA) development to VDZ and UST were not significantly different among patients with vs. without prior immunogenecity to anti-TNF therapy (2.7% vs. 0.9%; P = .54).

Study details: Findings are from a retrospective study of pediatric and adult patients with IBD who had previous exposure to anti-TNF drugs with ADA levels monitored and were subsequently exposed to VDZ or UST drug and had ADA levels checked during maintenance.

Disclosures: The study did not receive any funding. MC Dubinsky and RC Ungaro declared being consultant and/or advisory board member and/or receiving research support from various sources. The other authors declared no conflicts of interest.

Source: Costable NJ et al. Dig Dis Sci. 2021 May 21. doi: 10.1007/s10620-021-07046-7.

Key clinical point: Prior immunogenicity to anti-tumor necrosis factor (TNF) agents did not confer an increased risk for subsequent immunogenicity to ustekinumab (UST) or vedolizumab (VED) in patients with inflammatory bowel disease (IBD).

Major finding: The rates of anti-drug antibody (ADA) development to VDZ and UST were not significantly different among patients with vs. without prior immunogenecity to anti-TNF therapy (2.7% vs. 0.9%; P = .54).

Study details: Findings are from a retrospective study of pediatric and adult patients with IBD who had previous exposure to anti-TNF drugs with ADA levels monitored and were subsequently exposed to VDZ or UST drug and had ADA levels checked during maintenance.

Disclosures: The study did not receive any funding. MC Dubinsky and RC Ungaro declared being consultant and/or advisory board member and/or receiving research support from various sources. The other authors declared no conflicts of interest.

Source: Costable NJ et al. Dig Dis Sci. 2021 May 21. doi: 10.1007/s10620-021-07046-7.

Key clinical point: Prior immunogenicity to anti-tumor necrosis factor (TNF) agents did not confer an increased risk for subsequent immunogenicity to ustekinumab (UST) or vedolizumab (VED) in patients with inflammatory bowel disease (IBD).

Major finding: The rates of anti-drug antibody (ADA) development to VDZ and UST were not significantly different among patients with vs. without prior immunogenecity to anti-TNF therapy (2.7% vs. 0.9%; P = .54).

Study details: Findings are from a retrospective study of pediatric and adult patients with IBD who had previous exposure to anti-TNF drugs with ADA levels monitored and were subsequently exposed to VDZ or UST drug and had ADA levels checked during maintenance.

Disclosures: The study did not receive any funding. MC Dubinsky and RC Ungaro declared being consultant and/or advisory board member and/or receiving research support from various sources. The other authors declared no conflicts of interest.

Source: Costable NJ et al. Dig Dis Sci. 2021 May 21. doi: 10.1007/s10620-021-07046-7.

Key clinical point: Switching from adalimumab (ADA) originator to the biosimilar SB5 was safe with acceptable drug persistence and no change in biochemical activity over time in a large real-world cohort of patients with inflammatory bowel disease (IBD).

Major finding: At 26 and 52 weeks, 84.6% and 70.8% of patients who switched from ADA to SB5 remained on SB5 treatment, respectively. The proportion of patients in biochemical remission (P = .80), fecal biomarker remission (P = .40), and clinical remission (P = .53) was similar at baseline, week 26, and week 52 following the switch. Injection-site pain was the most commonly reported adverse event.

Study details: Findings are from a retrospective observational study of patients with IBD who underwent an elective switch from the ADA originator to the biosimilar SB5 (n=256).

Disclosures: No funding information was reported. LAAP Derikx, SI Siakavellas, N Plevris, and CW Lees declared serving as speaker, being on advisory boards, and/or receiving grant support from various sources. The other authors had no disclosures.

Source: Derikx LAAP et al. J Crohns Colitis. 2021 Jun 5. doi: 10.1093/ecco-jcc/jjab100.

Key clinical point: Switching from adalimumab (ADA) originator to the biosimilar SB5 was safe with acceptable drug persistence and no change in biochemical activity over time in a large real-world cohort of patients with inflammatory bowel disease (IBD).

Major finding: At 26 and 52 weeks, 84.6% and 70.8% of patients who switched from ADA to SB5 remained on SB5 treatment, respectively. The proportion of patients in biochemical remission (P = .80), fecal biomarker remission (P = .40), and clinical remission (P = .53) was similar at baseline, week 26, and week 52 following the switch. Injection-site pain was the most commonly reported adverse event.

Study details: Findings are from a retrospective observational study of patients with IBD who underwent an elective switch from the ADA originator to the biosimilar SB5 (n=256).

Disclosures: No funding information was reported. LAAP Derikx, SI Siakavellas, N Plevris, and CW Lees declared serving as speaker, being on advisory boards, and/or receiving grant support from various sources. The other authors had no disclosures.

Source: Derikx LAAP et al. J Crohns Colitis. 2021 Jun 5. doi: 10.1093/ecco-jcc/jjab100.

Key clinical point: Switching from adalimumab (ADA) originator to the biosimilar SB5 was safe with acceptable drug persistence and no change in biochemical activity over time in a large real-world cohort of patients with inflammatory bowel disease (IBD).

Major finding: At 26 and 52 weeks, 84.6% and 70.8% of patients who switched from ADA to SB5 remained on SB5 treatment, respectively. The proportion of patients in biochemical remission (P = .80), fecal biomarker remission (P = .40), and clinical remission (P = .53) was similar at baseline, week 26, and week 52 following the switch. Injection-site pain was the most commonly reported adverse event.

Study details: Findings are from a retrospective observational study of patients with IBD who underwent an elective switch from the ADA originator to the biosimilar SB5 (n=256).

Disclosures: No funding information was reported. LAAP Derikx, SI Siakavellas, N Plevris, and CW Lees declared serving as speaker, being on advisory boards, and/or receiving grant support from various sources. The other authors had no disclosures.

Source: Derikx LAAP et al. J Crohns Colitis. 2021 Jun 5. doi: 10.1093/ecco-jcc/jjab100.

Key clinical point: Completion of vaccination series against SARS-CoV-2 effectively reduced subsequent infection in a Veterans Affair cohort of patients with inflammatory bowel disease (IBD) with diverse exposure to immunosuppressive medications.

Major finding: Full vaccination (more than 7 days after the second dose) was associated with a 69% reduced risk for SARS-CoV-2 infection compared with unvaccinated individuals (hazard ratio, 0.31; P less than .001). The corresponding vaccine effectiveness for full and partial vaccination status was 80.4% and 25.1%, respectively.

Study details: This retrospective study used data from Veterans Health Administration to evaluate 14,697 patients with a diagnosis of ulcerative colitis or Crohn’s disease and diverse exposure to immunosuppressive agents. About 45.2% and 54.8% of patients received the Pfizer and Moderna vaccine with 91.2% of Pfizer and 88.7% of Moderna patients receiving both vaccine doses.

Disclosures: The study did not receive any funding. Dr. N Khan declared receiving research grant from Pfizer, Luitpold, Takeda Pharmaceuticals, and Samsung BioEpis. Dr. N Mahmud is supported by an American College of Gastroenterology junior faculty development award and a Leonard Davis Institute COVID-19 rapid response grant.

Source: Khan N et al. Gastroenterology. 2021 May 25. doi: 10.1053/j.gastro.2021.05.044.

Key clinical point: Completion of vaccination series against SARS-CoV-2 effectively reduced subsequent infection in a Veterans Affair cohort of patients with inflammatory bowel disease (IBD) with diverse exposure to immunosuppressive medications.

Major finding: Full vaccination (more than 7 days after the second dose) was associated with a 69% reduced risk for SARS-CoV-2 infection compared with unvaccinated individuals (hazard ratio, 0.31; P less than .001). The corresponding vaccine effectiveness for full and partial vaccination status was 80.4% and 25.1%, respectively.

Study details: This retrospective study used data from Veterans Health Administration to evaluate 14,697 patients with a diagnosis of ulcerative colitis or Crohn’s disease and diverse exposure to immunosuppressive agents. About 45.2% and 54.8% of patients received the Pfizer and Moderna vaccine with 91.2% of Pfizer and 88.7% of Moderna patients receiving both vaccine doses.

Disclosures: The study did not receive any funding. Dr. N Khan declared receiving research grant from Pfizer, Luitpold, Takeda Pharmaceuticals, and Samsung BioEpis. Dr. N Mahmud is supported by an American College of Gastroenterology junior faculty development award and a Leonard Davis Institute COVID-19 rapid response grant.

Source: Khan N et al. Gastroenterology. 2021 May 25. doi: 10.1053/j.gastro.2021.05.044.

Key clinical point: Completion of vaccination series against SARS-CoV-2 effectively reduced subsequent infection in a Veterans Affair cohort of patients with inflammatory bowel disease (IBD) with diverse exposure to immunosuppressive medications.

Major finding: Full vaccination (more than 7 days after the second dose) was associated with a 69% reduced risk for SARS-CoV-2 infection compared with unvaccinated individuals (hazard ratio, 0.31; P less than .001). The corresponding vaccine effectiveness for full and partial vaccination status was 80.4% and 25.1%, respectively.

Study details: This retrospective study used data from Veterans Health Administration to evaluate 14,697 patients with a diagnosis of ulcerative colitis or Crohn’s disease and diverse exposure to immunosuppressive agents. About 45.2% and 54.8% of patients received the Pfizer and Moderna vaccine with 91.2% of Pfizer and 88.7% of Moderna patients receiving both vaccine doses.

Disclosures: The study did not receive any funding. Dr. N Khan declared receiving research grant from Pfizer, Luitpold, Takeda Pharmaceuticals, and Samsung BioEpis. Dr. N Mahmud is supported by an American College of Gastroenterology junior faculty development award and a Leonard Davis Institute COVID-19 rapid response grant.

Source: Khan N et al. Gastroenterology. 2021 May 25. doi: 10.1053/j.gastro.2021.05.044.

Key clinical point: Filgotinib 200 mg once daily for up to 58 weeks effectively induced and maintained clinical remission (CR) and was well tolerated compared with placebo in both biologic-naive and biologic-experienced patients with moderately to severely active ulcerative colitis.

Major finding: CR was achieved by a greater proportion of patients treated with filgotinib 200 mg vs. placebo in both biologic-naïve (absolute difference [AD], 10.8%; P = .0157) and biologic-experienced (AD, 7.2%; P = .0103) patients at weeks 10 and 58 (AD, 26.0%; P less than .0001). Incidence of adverse events of interest and serious adverse events was similar across treatment arms.

Study details: Findings are from phase 2b/3 SELECTION trial involving 659 biologic-naive and 689 biologic-experienced patients with moderately to severely active ulcerative colitis randomly allocated to oral filgotinib 200 mg, filgotinib 100 mg, or placebo once daily.

Disclosures: The study was funded by Gilead Sciences. Some of the authors declared receiving grants, personal/consultancy fees, travel expense and/or non-financial support from; being an employee of; and/or holding stocks of various sources including Gilead Sciences.

Source: Feagan BG et al. Lancet. 2021 Jun 3. doi: 10.1016/S0140-6736(21)00666-8.

Key clinical point: Filgotinib 200 mg once daily for up to 58 weeks effectively induced and maintained clinical remission (CR) and was well tolerated compared with placebo in both biologic-naive and biologic-experienced patients with moderately to severely active ulcerative colitis.

Major finding: CR was achieved by a greater proportion of patients treated with filgotinib 200 mg vs. placebo in both biologic-naïve (absolute difference [AD], 10.8%; P = .0157) and biologic-experienced (AD, 7.2%; P = .0103) patients at weeks 10 and 58 (AD, 26.0%; P less than .0001). Incidence of adverse events of interest and serious adverse events was similar across treatment arms.

Study details: Findings are from phase 2b/3 SELECTION trial involving 659 biologic-naive and 689 biologic-experienced patients with moderately to severely active ulcerative colitis randomly allocated to oral filgotinib 200 mg, filgotinib 100 mg, or placebo once daily.

Disclosures: The study was funded by Gilead Sciences. Some of the authors declared receiving grants, personal/consultancy fees, travel expense and/or non-financial support from; being an employee of; and/or holding stocks of various sources including Gilead Sciences.

Source: Feagan BG et al. Lancet. 2021 Jun 3. doi: 10.1016/S0140-6736(21)00666-8.

Key clinical point: Filgotinib 200 mg once daily for up to 58 weeks effectively induced and maintained clinical remission (CR) and was well tolerated compared with placebo in both biologic-naive and biologic-experienced patients with moderately to severely active ulcerative colitis.

Major finding: CR was achieved by a greater proportion of patients treated with filgotinib 200 mg vs. placebo in both biologic-naïve (absolute difference [AD], 10.8%; P = .0157) and biologic-experienced (AD, 7.2%; P = .0103) patients at weeks 10 and 58 (AD, 26.0%; P less than .0001). Incidence of adverse events of interest and serious adverse events was similar across treatment arms.

Study details: Findings are from phase 2b/3 SELECTION trial involving 659 biologic-naive and 689 biologic-experienced patients with moderately to severely active ulcerative colitis randomly allocated to oral filgotinib 200 mg, filgotinib 100 mg, or placebo once daily.

Disclosures: The study was funded by Gilead Sciences. Some of the authors declared receiving grants, personal/consultancy fees, travel expense and/or non-financial support from; being an employee of; and/or holding stocks of various sources including Gilead Sciences.

Source: Feagan BG et al. Lancet. 2021 Jun 3. doi: 10.1016/S0140-6736(21)00666-8.

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.

The American College of Gastroenterology has issued new guidelines on management of Clostridioides difficile infection that now include roles for fecal microbial transplant (FMT), combination testing, and bezlotoxumab.

The ACG’s previous guidelines on the diagnosis, management, and treatment of what was then still called Clostridium difficile were published in 2013. Since then, the organism’s name changed to Clostridioides difficile, and that’s just the beginning of the changes reflected in the scientific literature, wrote lead author Colleen R. Kelly, MD, of Brown University, Providence, R.I., and colleagues.

“Other developments include the increased recognition of diagnostic challenges in the era of nucleic acid amplification–based testing, new therapeutic options for treatment and prevention of recurrence, and increasing evidence to support fecal microbiota transplantation (FMT) in recurrent and severe infection,” the authors said.

The guidelines, published in the American Journal of Gastroenterology, include 23 graded recommendations addressing issues of prevention, diagnosis, treatment, prevention of recurrence, and guidance for special populations in the management of C. difficile infection (CDI).
 

New faces among familiar ones

In terms of diagnosis, the new guidelines recommend using both a highly sensitive testing modality and a highly specific one to help distinguish colonization from active infection. Specifically, the authors recommend that stool is first tested using a highly sensitive test, either nucleic acid amplification testing or glutamate dehydrogenase, followed by an enzyme immunoassays for its high specificity.

Changes to treatment recommendations include the initial use of oral vancomycin or oral fidaxomicin for cases of nonsevere CDI. Oral metronidazole may be considered for initial nonsevere CDI in low-risk patients, the authors noted. The evidence is strong for the continued recommendations of vancomycin (125 mg four times daily for 10 days) and fidaxomicin (200 mg twice daily for 10 days) for patients with severe CDI. For patients with fulminant CDI, the recommendations call for medical therapy including volume resuscitation and oral vancomycin, although combination therapy with parenteral metronidazole may be considered despite the very low quality of evidence.

A notable update to the guidelines is the recommendation of fecal microbiota transplant (FMT) for both severe and fulminant CDI cases that are resistant to antibiotics and to prevent recurrence in at-risk patients. Although the quality of evidence is ranked as low, the recommendation is strong, the authors wrote. “Beyond improved cure rates, FMT may result in decreased rates of CDI-related colectomy and sepsis and may offer survival benefit in this critically ill patient population.” However, most patients in studies of FMT required multiple treatments in combination with anti-CDI antibiotics.

Other recommendations to prevent recurrence include oral vancomycin prophylaxis during the subsequent use of systemic antibiotics in patients with a history of CDI. The guidelines also recommend bezlotoxumab for prevention of CDI recurrence in high-risk patients, and advise against discontinuing antisecretory therapy in CDI patients if there is an appropriate indication for use.

Based on the lack of quality evidence, the guidelines recommend against the use of probiotics for preventing CDI in patients being treated with antibiotics and for prevention of recurrent infection.
 

Special populations

For patients with inflammatory bowel disease, the guidelines recommend C. difficile testing when these individuals present with acute flares and diarrhea, and the use of vancomycin for treatment. In addition, the authors strongly recommended FMT for recurrent CDI in these patients. For pregnant, postpartum, and breastfeeding patients with CDI, the guidelines recommend vancomycin, and either vancomycin or fidaxomicin may be used for treating CDI in immunocompromised patients, the authors noted.

The updated guidelines are designed to complement those issued by the Infections Disease Society of America and Society of Healthcare Epidemiologists of America, the researchers noted.
 

Reflecting the research

The previous guidelines for C. difficile were issued in 2013, and much has changed since then in terms of epidemiology, diagnosis, treatment, and infection control, Sahil Khanna, MBBS, MS, of the Mayo Clinic, Rochester, Minn., said in an interview.

Notably, diagnostic testing has “made leaps and bounds” and new treatments have become available that were not included in earlier guidelines, said Dr. Khanna. In particular, the new guidelines are recommending a two-step diagnostic assay; “the diagnostic algorithm has changed, and hopefully that will help us change practice” to identify active infection more quickly and efficiently.

Another important update is the recommendation of fidaxomicin as an option for initial nonfulminant CDI as an alternative to vancomycin, Dr. Khanna said, noting that metronidazole remains an option for low-risk patients. An additional change is the advice to use a different treatment for a second recurrent infection rather than repeating the initial treatment.  

The recommendation of bezlotoxumab for prevention of CDI recurrence in patients who are at high risk of recurrence is the first time this drug has appeared in major guidelines, Dr. Khanna observed.

The recommendation in support of fecal microbiota transplant is a key update to the management of CDI, including the guidance that the procedure can be repeated if necessary, he said.

Looking ahead, “Additional research is needed to fully understand the best testing algorithms for CDI,” Dr. Khanna explained. “More studies also are needed to show how FMT fully fits into the picture, and some current studies are looking at its potential earlier in the course of infection.”

The guidelines were developed in collaboration with the Practice Parameters Committee of the American College of Gastroenterology and received no outside funding. Dr. Kelly disclosed serving as a site investigator of a clinical trial for Finch Therapeutics and is an unpaid clinical advisory board member for OpenBiome. Dr. Khanna has coauthored previous guidelines on C. difficile. He disclosed consulting relationships with Finch, GlaxoSmithKline, Jetson, ProbioTech, and Shire/Takeda, as well as research support from Rebiotix, Seres, and Vedanta.

The American College of Gastroenterology has issued new guidelines on management of Clostridioides difficile infection that now include roles for fecal microbial transplant (FMT), combination testing, and bezlotoxumab.

The ACG’s previous guidelines on the diagnosis, management, and treatment of what was then still called Clostridium difficile were published in 2013. Since then, the organism’s name changed to Clostridioides difficile, and that’s just the beginning of the changes reflected in the scientific literature, wrote lead author Colleen R. Kelly, MD, of Brown University, Providence, R.I., and colleagues.

“Other developments include the increased recognition of diagnostic challenges in the era of nucleic acid amplification–based testing, new therapeutic options for treatment and prevention of recurrence, and increasing evidence to support fecal microbiota transplantation (FMT) in recurrent and severe infection,” the authors said.

The guidelines, published in the American Journal of Gastroenterology, include 23 graded recommendations addressing issues of prevention, diagnosis, treatment, prevention of recurrence, and guidance for special populations in the management of C. difficile infection (CDI).
 

New faces among familiar ones

In terms of diagnosis, the new guidelines recommend using both a highly sensitive testing modality and a highly specific one to help distinguish colonization from active infection. Specifically, the authors recommend that stool is first tested using a highly sensitive test, either nucleic acid amplification testing or glutamate dehydrogenase, followed by an enzyme immunoassays for its high specificity.

Changes to treatment recommendations include the initial use of oral vancomycin or oral fidaxomicin for cases of nonsevere CDI. Oral metronidazole may be considered for initial nonsevere CDI in low-risk patients, the authors noted. The evidence is strong for the continued recommendations of vancomycin (125 mg four times daily for 10 days) and fidaxomicin (200 mg twice daily for 10 days) for patients with severe CDI. For patients with fulminant CDI, the recommendations call for medical therapy including volume resuscitation and oral vancomycin, although combination therapy with parenteral metronidazole may be considered despite the very low quality of evidence.

A notable update to the guidelines is the recommendation of fecal microbiota transplant (FMT) for both severe and fulminant CDI cases that are resistant to antibiotics and to prevent recurrence in at-risk patients. Although the quality of evidence is ranked as low, the recommendation is strong, the authors wrote. “Beyond improved cure rates, FMT may result in decreased rates of CDI-related colectomy and sepsis and may offer survival benefit in this critically ill patient population.” However, most patients in studies of FMT required multiple treatments in combination with anti-CDI antibiotics.

Other recommendations to prevent recurrence include oral vancomycin prophylaxis during the subsequent use of systemic antibiotics in patients with a history of CDI. The guidelines also recommend bezlotoxumab for prevention of CDI recurrence in high-risk patients, and advise against discontinuing antisecretory therapy in CDI patients if there is an appropriate indication for use.

Based on the lack of quality evidence, the guidelines recommend against the use of probiotics for preventing CDI in patients being treated with antibiotics and for prevention of recurrent infection.
 

Special populations

For patients with inflammatory bowel disease, the guidelines recommend C. difficile testing when these individuals present with acute flares and diarrhea, and the use of vancomycin for treatment. In addition, the authors strongly recommended FMT for recurrent CDI in these patients. For pregnant, postpartum, and breastfeeding patients with CDI, the guidelines recommend vancomycin, and either vancomycin or fidaxomicin may be used for treating CDI in immunocompromised patients, the authors noted.

The updated guidelines are designed to complement those issued by the Infections Disease Society of America and Society of Healthcare Epidemiologists of America, the researchers noted.
 

Reflecting the research

The previous guidelines for C. difficile were issued in 2013, and much has changed since then in terms of epidemiology, diagnosis, treatment, and infection control, Sahil Khanna, MBBS, MS, of the Mayo Clinic, Rochester, Minn., said in an interview.

Notably, diagnostic testing has “made leaps and bounds” and new treatments have become available that were not included in earlier guidelines, said Dr. Khanna. In particular, the new guidelines are recommending a two-step diagnostic assay; “the diagnostic algorithm has changed, and hopefully that will help us change practice” to identify active infection more quickly and efficiently.

Another important update is the recommendation of fidaxomicin as an option for initial nonfulminant CDI as an alternative to vancomycin, Dr. Khanna said, noting that metronidazole remains an option for low-risk patients. An additional change is the advice to use a different treatment for a second recurrent infection rather than repeating the initial treatment.  

The recommendation of bezlotoxumab for prevention of CDI recurrence in patients who are at high risk of recurrence is the first time this drug has appeared in major guidelines, Dr. Khanna observed.

The recommendation in support of fecal microbiota transplant is a key update to the management of CDI, including the guidance that the procedure can be repeated if necessary, he said.

Looking ahead, “Additional research is needed to fully understand the best testing algorithms for CDI,” Dr. Khanna explained. “More studies also are needed to show how FMT fully fits into the picture, and some current studies are looking at its potential earlier in the course of infection.”

The guidelines were developed in collaboration with the Practice Parameters Committee of the American College of Gastroenterology and received no outside funding. Dr. Kelly disclosed serving as a site investigator of a clinical trial for Finch Therapeutics and is an unpaid clinical advisory board member for OpenBiome. Dr. Khanna has coauthored previous guidelines on C. difficile. He disclosed consulting relationships with Finch, GlaxoSmithKline, Jetson, ProbioTech, and Shire/Takeda, as well as research support from Rebiotix, Seres, and Vedanta.

The American College of Gastroenterology has issued new guidelines on management of Clostridioides difficile infection that now include roles for fecal microbial transplant (FMT), combination testing, and bezlotoxumab.

The ACG’s previous guidelines on the diagnosis, management, and treatment of what was then still called Clostridium difficile were published in 2013. Since then, the organism’s name changed to Clostridioides difficile, and that’s just the beginning of the changes reflected in the scientific literature, wrote lead author Colleen R. Kelly, MD, of Brown University, Providence, R.I., and colleagues.

“Other developments include the increased recognition of diagnostic challenges in the era of nucleic acid amplification–based testing, new therapeutic options for treatment and prevention of recurrence, and increasing evidence to support fecal microbiota transplantation (FMT) in recurrent and severe infection,” the authors said.

The guidelines, published in the American Journal of Gastroenterology, include 23 graded recommendations addressing issues of prevention, diagnosis, treatment, prevention of recurrence, and guidance for special populations in the management of C. difficile infection (CDI).
 

New faces among familiar ones

In terms of diagnosis, the new guidelines recommend using both a highly sensitive testing modality and a highly specific one to help distinguish colonization from active infection. Specifically, the authors recommend that stool is first tested using a highly sensitive test, either nucleic acid amplification testing or glutamate dehydrogenase, followed by an enzyme immunoassays for its high specificity.

Changes to treatment recommendations include the initial use of oral vancomycin or oral fidaxomicin for cases of nonsevere CDI. Oral metronidazole may be considered for initial nonsevere CDI in low-risk patients, the authors noted. The evidence is strong for the continued recommendations of vancomycin (125 mg four times daily for 10 days) and fidaxomicin (200 mg twice daily for 10 days) for patients with severe CDI. For patients with fulminant CDI, the recommendations call for medical therapy including volume resuscitation and oral vancomycin, although combination therapy with parenteral metronidazole may be considered despite the very low quality of evidence.

A notable update to the guidelines is the recommendation of fecal microbiota transplant (FMT) for both severe and fulminant CDI cases that are resistant to antibiotics and to prevent recurrence in at-risk patients. Although the quality of evidence is ranked as low, the recommendation is strong, the authors wrote. “Beyond improved cure rates, FMT may result in decreased rates of CDI-related colectomy and sepsis and may offer survival benefit in this critically ill patient population.” However, most patients in studies of FMT required multiple treatments in combination with anti-CDI antibiotics.

Other recommendations to prevent recurrence include oral vancomycin prophylaxis during the subsequent use of systemic antibiotics in patients with a history of CDI. The guidelines also recommend bezlotoxumab for prevention of CDI recurrence in high-risk patients, and advise against discontinuing antisecretory therapy in CDI patients if there is an appropriate indication for use.

Based on the lack of quality evidence, the guidelines recommend against the use of probiotics for preventing CDI in patients being treated with antibiotics and for prevention of recurrent infection.
 

Special populations

For patients with inflammatory bowel disease, the guidelines recommend C. difficile testing when these individuals present with acute flares and diarrhea, and the use of vancomycin for treatment. In addition, the authors strongly recommended FMT for recurrent CDI in these patients. For pregnant, postpartum, and breastfeeding patients with CDI, the guidelines recommend vancomycin, and either vancomycin or fidaxomicin may be used for treating CDI in immunocompromised patients, the authors noted.

The updated guidelines are designed to complement those issued by the Infections Disease Society of America and Society of Healthcare Epidemiologists of America, the researchers noted.
 

Reflecting the research

The previous guidelines for C. difficile were issued in 2013, and much has changed since then in terms of epidemiology, diagnosis, treatment, and infection control, Sahil Khanna, MBBS, MS, of the Mayo Clinic, Rochester, Minn., said in an interview.

Notably, diagnostic testing has “made leaps and bounds” and new treatments have become available that were not included in earlier guidelines, said Dr. Khanna. In particular, the new guidelines are recommending a two-step diagnostic assay; “the diagnostic algorithm has changed, and hopefully that will help us change practice” to identify active infection more quickly and efficiently.

Another important update is the recommendation of fidaxomicin as an option for initial nonfulminant CDI as an alternative to vancomycin, Dr. Khanna said, noting that metronidazole remains an option for low-risk patients. An additional change is the advice to use a different treatment for a second recurrent infection rather than repeating the initial treatment.  

The recommendation of bezlotoxumab for prevention of CDI recurrence in patients who are at high risk of recurrence is the first time this drug has appeared in major guidelines, Dr. Khanna observed.

The recommendation in support of fecal microbiota transplant is a key update to the management of CDI, including the guidance that the procedure can be repeated if necessary, he said.

Looking ahead, “Additional research is needed to fully understand the best testing algorithms for CDI,” Dr. Khanna explained. “More studies also are needed to show how FMT fully fits into the picture, and some current studies are looking at its potential earlier in the course of infection.”

The guidelines were developed in collaboration with the Practice Parameters Committee of the American College of Gastroenterology and received no outside funding. Dr. Kelly disclosed serving as a site investigator of a clinical trial for Finch Therapeutics and is an unpaid clinical advisory board member for OpenBiome. Dr. Khanna has coauthored previous guidelines on C. difficile. He disclosed consulting relationships with Finch, GlaxoSmithKline, Jetson, ProbioTech, and Shire/Takeda, as well as research support from Rebiotix, Seres, and Vedanta.