IBD: Anti-TNF doses often increased without evidence of inflammation

Clinicians frequently increase doses of anti–tumor necrosis factor (anti-TNF) agents for patients with inflammatory bowel disease (IBD) without objective evidence of active inflammation, based on a retrospective study.

This strategy may be ineffective and expensive, according to lead author Evan D. Elias, MD, of the University of Manitoba, Winnipeg, Canada, and colleagues, who noted that worsening symptoms may have noninflammatory causes, such as coexisting functional disorders.

“Objective evidence of active inflammation is a key part of [the dose escalation] process,” the investigators wrote in the Journal of Clinical Gastroenterology, “however, there are no data assessing whether an adequate evaluation of the cause of persistent gastrointestinal symptoms is routinely undertaken in clinical practice.”

To address this knowledge gap, Dr. Elias and colleagues conducted a retrospective study involving 23 physicians in Manitoba who initiated anti-TNF therapy in 838 patients with IBD during 2005-2016. The primary outcome was rate of dose escalation within 1 year. Secondarily, the investigators audited 11 out of 23 prescribers to determine how frequently patients receiving increased doses underwent objective assessment of inflammation, both in general and in the 90 days preceding dose escalation.

Of note, therapeutic drug monitoring, fecal calprotectin testing, and transabdominal ultrasound were not commonly available to prescribers during the study period.

Within 1 year, almost one-third of patients (32.9%) received increased doses of either adalimumab or infliximab, with no significant difference in escalation practices between the two agents. After approximately 2 years, increased doses were prescribed for almost half of the patients (49%), with a median time to dose increase of 17.4 months.

Patients with ulcerative colitis were 83% more likely to receive increased doses than were those with Crohn’s disease (P = .0001), and doses were typically escalated at an earlier date (7.1 vs. 11.1 months). In contrast, dose escalation was not associated with a variety of other patient factors, such as sex, age, or baseline laboratory values.

Comprehensive data from 11 prescribers showed that 70.8% of patients who received increased doses underwent some form of testing to assess inflammation, but only 24.7% of them had objective evidence of inflammatory activity that supported the dose increase.

Raymond K. Cross Jr., MD, MS, AGAF, FACG, director of the IBD program at the University of Maryland, Baltimore County, said that the findings were “not surprising.”

Dr. Cross said that patients with IBD should ideally undergo testing for drug levels and inflammatory activity prior to dose escalation, but this one-size-fits-all approach doesn’t always translate to real-world practice.

“There’s the science, and there’s the practical,” he said, noting that dose escalation may precede testing “in an effort to be efficient and decrease suffering.” This includes cases in which patients receive an earlier or increased dose to bridge the gap between worsening of symptoms and completion of diagnostics.

Dr. Cross also pointed out that patients with ulcerative colitis typically have a strong correlation between symptoms and level of inflammation.

“If [a patient with ulcerative colitis] has bloody diarrhea, it’s 90% or so that they’re going to have active inflammation in their colon, so I feel less obligated to do those checks in an ulcerative colitis patient who has classic symptoms,” he said.

Byron Vaughn, MD, codirector of the IBD program at the University of Minnesota, Minneapolis, suggested that the study by Elias and colleagues “serves as an important reminder to follow the tenets of a treat-to-target strategy, which include regular assessment of objective markers of inflammation specific to IBD before and after a dose adjustment.”

Still, like Dr. Cross, Dr. Vaughn noted that dose escalation without additional testing “may be reasonable” in certain scenarios, such as when patients with ulcerative colitis have bloody diarrhea and tenesmus or for patients with perianal Crohn’s disease.

“A key limitation of this study is the lack of drug concentration monitoring,” Dr. Vaughn said. “Due to the immunogenicity of anti-TNF medications there is a strong rationale for proactive dose adjustments to avoid low or undetectable concentrations and subsequent antibody formation. However, as the authors point out, this is unlikely to be a major factor in this particular study as drug concentration measurement was not routinely available over the study period.”

The investigators disclosed relationships with AbbVie, Ferring, Janssen, and others. Dr. Vaughn disclosed relationships with AbbVie, Celgene, Genentech, Takeda, and others. Dr. Cross disclosed relationships with AbbVie, Janssen, and Samsung Bioepis.

SOURCE: Elias ED et al. J Clin Gastroenterol. 2020 Jul 17. doi: 10.1097/MCG.0000000000001391.

Clinicians frequently increase doses of anti–tumor necrosis factor (anti-TNF) agents for patients with inflammatory bowel disease (IBD) without objective evidence of active inflammation, based on a retrospective study.

This strategy may be ineffective and expensive, according to lead author Evan D. Elias, MD, of the University of Manitoba, Winnipeg, Canada, and colleagues, who noted that worsening symptoms may have noninflammatory causes, such as coexisting functional disorders.

“Objective evidence of active inflammation is a key part of [the dose escalation] process,” the investigators wrote in the Journal of Clinical Gastroenterology, “however, there are no data assessing whether an adequate evaluation of the cause of persistent gastrointestinal symptoms is routinely undertaken in clinical practice.”

To address this knowledge gap, Dr. Elias and colleagues conducted a retrospective study involving 23 physicians in Manitoba who initiated anti-TNF therapy in 838 patients with IBD during 2005-2016. The primary outcome was rate of dose escalation within 1 year. Secondarily, the investigators audited 11 out of 23 prescribers to determine how frequently patients receiving increased doses underwent objective assessment of inflammation, both in general and in the 90 days preceding dose escalation.

Of note, therapeutic drug monitoring, fecal calprotectin testing, and transabdominal ultrasound were not commonly available to prescribers during the study period.

Within 1 year, almost one-third of patients (32.9%) received increased doses of either adalimumab or infliximab, with no significant difference in escalation practices between the two agents. After approximately 2 years, increased doses were prescribed for almost half of the patients (49%), with a median time to dose increase of 17.4 months.

Patients with ulcerative colitis were 83% more likely to receive increased doses than were those with Crohn’s disease (P = .0001), and doses were typically escalated at an earlier date (7.1 vs. 11.1 months). In contrast, dose escalation was not associated with a variety of other patient factors, such as sex, age, or baseline laboratory values.

Comprehensive data from 11 prescribers showed that 70.8% of patients who received increased doses underwent some form of testing to assess inflammation, but only 24.7% of them had objective evidence of inflammatory activity that supported the dose increase.

Raymond K. Cross Jr., MD, MS, AGAF, FACG, director of the IBD program at the University of Maryland, Baltimore County, said that the findings were “not surprising.”

Dr. Cross said that patients with IBD should ideally undergo testing for drug levels and inflammatory activity prior to dose escalation, but this one-size-fits-all approach doesn’t always translate to real-world practice.

“There’s the science, and there’s the practical,” he said, noting that dose escalation may precede testing “in an effort to be efficient and decrease suffering.” This includes cases in which patients receive an earlier or increased dose to bridge the gap between worsening of symptoms and completion of diagnostics.

Dr. Cross also pointed out that patients with ulcerative colitis typically have a strong correlation between symptoms and level of inflammation.

“If [a patient with ulcerative colitis] has bloody diarrhea, it’s 90% or so that they’re going to have active inflammation in their colon, so I feel less obligated to do those checks in an ulcerative colitis patient who has classic symptoms,” he said.

Byron Vaughn, MD, codirector of the IBD program at the University of Minnesota, Minneapolis, suggested that the study by Elias and colleagues “serves as an important reminder to follow the tenets of a treat-to-target strategy, which include regular assessment of objective markers of inflammation specific to IBD before and after a dose adjustment.”

Still, like Dr. Cross, Dr. Vaughn noted that dose escalation without additional testing “may be reasonable” in certain scenarios, such as when patients with ulcerative colitis have bloody diarrhea and tenesmus or for patients with perianal Crohn’s disease.

“A key limitation of this study is the lack of drug concentration monitoring,” Dr. Vaughn said. “Due to the immunogenicity of anti-TNF medications there is a strong rationale for proactive dose adjustments to avoid low or undetectable concentrations and subsequent antibody formation. However, as the authors point out, this is unlikely to be a major factor in this particular study as drug concentration measurement was not routinely available over the study period.”

The investigators disclosed relationships with AbbVie, Ferring, Janssen, and others. Dr. Vaughn disclosed relationships with AbbVie, Celgene, Genentech, Takeda, and others. Dr. Cross disclosed relationships with AbbVie, Janssen, and Samsung Bioepis.

SOURCE: Elias ED et al. J Clin Gastroenterol. 2020 Jul 17. doi: 10.1097/MCG.0000000000001391.

Clinicians frequently increase doses of anti–tumor necrosis factor (anti-TNF) agents for patients with inflammatory bowel disease (IBD) without objective evidence of active inflammation, based on a retrospective study.

This strategy may be ineffective and expensive, according to lead author Evan D. Elias, MD, of the University of Manitoba, Winnipeg, Canada, and colleagues, who noted that worsening symptoms may have noninflammatory causes, such as coexisting functional disorders.

“Objective evidence of active inflammation is a key part of [the dose escalation] process,” the investigators wrote in the Journal of Clinical Gastroenterology, “however, there are no data assessing whether an adequate evaluation of the cause of persistent gastrointestinal symptoms is routinely undertaken in clinical practice.”

To address this knowledge gap, Dr. Elias and colleagues conducted a retrospective study involving 23 physicians in Manitoba who initiated anti-TNF therapy in 838 patients with IBD during 2005-2016. The primary outcome was rate of dose escalation within 1 year. Secondarily, the investigators audited 11 out of 23 prescribers to determine how frequently patients receiving increased doses underwent objective assessment of inflammation, both in general and in the 90 days preceding dose escalation.

Of note, therapeutic drug monitoring, fecal calprotectin testing, and transabdominal ultrasound were not commonly available to prescribers during the study period.

Within 1 year, almost one-third of patients (32.9%) received increased doses of either adalimumab or infliximab, with no significant difference in escalation practices between the two agents. After approximately 2 years, increased doses were prescribed for almost half of the patients (49%), with a median time to dose increase of 17.4 months.

Patients with ulcerative colitis were 83% more likely to receive increased doses than were those with Crohn’s disease (P = .0001), and doses were typically escalated at an earlier date (7.1 vs. 11.1 months). In contrast, dose escalation was not associated with a variety of other patient factors, such as sex, age, or baseline laboratory values.

Comprehensive data from 11 prescribers showed that 70.8% of patients who received increased doses underwent some form of testing to assess inflammation, but only 24.7% of them had objective evidence of inflammatory activity that supported the dose increase.

Raymond K. Cross Jr., MD, MS, AGAF, FACG, director of the IBD program at the University of Maryland, Baltimore County, said that the findings were “not surprising.”

Dr. Cross said that patients with IBD should ideally undergo testing for drug levels and inflammatory activity prior to dose escalation, but this one-size-fits-all approach doesn’t always translate to real-world practice.

“There’s the science, and there’s the practical,” he said, noting that dose escalation may precede testing “in an effort to be efficient and decrease suffering.” This includes cases in which patients receive an earlier or increased dose to bridge the gap between worsening of symptoms and completion of diagnostics.

Dr. Cross also pointed out that patients with ulcerative colitis typically have a strong correlation between symptoms and level of inflammation.

“If [a patient with ulcerative colitis] has bloody diarrhea, it’s 90% or so that they’re going to have active inflammation in their colon, so I feel less obligated to do those checks in an ulcerative colitis patient who has classic symptoms,” he said.

Byron Vaughn, MD, codirector of the IBD program at the University of Minnesota, Minneapolis, suggested that the study by Elias and colleagues “serves as an important reminder to follow the tenets of a treat-to-target strategy, which include regular assessment of objective markers of inflammation specific to IBD before and after a dose adjustment.”

Still, like Dr. Cross, Dr. Vaughn noted that dose escalation without additional testing “may be reasonable” in certain scenarios, such as when patients with ulcerative colitis have bloody diarrhea and tenesmus or for patients with perianal Crohn’s disease.

“A key limitation of this study is the lack of drug concentration monitoring,” Dr. Vaughn said. “Due to the immunogenicity of anti-TNF medications there is a strong rationale for proactive dose adjustments to avoid low or undetectable concentrations and subsequent antibody formation. However, as the authors point out, this is unlikely to be a major factor in this particular study as drug concentration measurement was not routinely available over the study period.”

The investigators disclosed relationships with AbbVie, Ferring, Janssen, and others. Dr. Vaughn disclosed relationships with AbbVie, Celgene, Genentech, Takeda, and others. Dr. Cross disclosed relationships with AbbVie, Janssen, and Samsung Bioepis.

SOURCE: Elias ED et al. J Clin Gastroenterol. 2020 Jul 17. doi: 10.1097/MCG.0000000000001391.