The findings of the current study are consistent with those of the only epidemiological study conducted in the state of Rio Grande do Sul, which showed a higher prevalence of CD than UC (72.45% vs 27.54%), a predominance of female patients (57.5% vs 42.5%), and a higher incidence in patients aged 20 to 60 years, predominantly between the ages 30 and 40 years [3].

Regarding CD location, perianal involvement was observed in 48% of patients. Regarding UC extent, most patients had distal UC (E2; 41%), followed by ulcerative proctitis (E1; 35%) and extensive UC (E3; 24%). A recent systematic review of a Spanish population found heterogeneous data regarding the location of the CD lesion: ileal involvement (L1) occurred more frequently in the adult and older population than in the pediatric population, whereas ileocolonic involvement (L3) showed the opposite trend. The frequency of perianal disease was higher in the pediatric population than in the adult population. Similar to our findings, in UC, there was a predominance of the E2 extent [4].

One of the first studies to suggest a benefit of early biologic therapy was the TOP-DOWN trial [5]. Combined immunosuppression (immunobiologic agent + immunomodulator) was more effective than conventional management (corticosteroids and immunomodulator alone) for induction of remission and reduction of corticosteroid use in patients who had been recently diagnosed with CD. The authors suggested that initiation of more intensive treatment earlier in the course of the disease could result in better outcomes [5]. In our study, 72.6% of patients used at least one immunobiologic agent, mostly anti-TNFs (80%), with the initiation of treatment between 6 and 12 months after diagnosis. Combination therapy (immunobiologic agent combined with an immunomodulator) was used in 70% of patients.

There is currently a more robust advanced therapeutic arsenal, with agents possessing different mechanisms of action and routes of delivery, including oral use in the case of small molecules. In general, the main consensus guidelines consider anti-TNFs an excellent therapeutic option [6-9]. The choice of the first immunobiologic agent prescription is very important, because, in general, the response is better in patients naive to the first agent than in those in whom other mechanisms of action have failed. Therefore, many variables should be taken into consideration. Since the publication of the VARSITY study, ADA has been the preferred option in CD but not in UC, which may be the reason why, in our study, ADA was used in approximately 60% of patients with CD, but in only 6% with UC [10]. Drugs with novel mechanisms of action, such as anti-integrin (VDZ), anti-interleukin (UST), and oral small molecules (TOFA), have recently been incorporated into the therapeutic arsenal and present certain access restrictions in both private and public sectors, but especially in the public health system, which may have contributed to their lower rates of use in our study.

Endoscopic healing is considered an important treatment goal in clinical trials and in clinical practice for patients with IBD, as it is associated with sustained clinical remission, corticosteroidfree remission, and reduced hospitalization and surgery rates [6-9]. The STRIDE-II consensus stratifies the therapeutic targets in the treatment of patients with IBD into short-, medium-, and long-term targets, and one of the recommended long-term targets is endoscopic remission between 6 and 9 months [11]. In our study, endoscopic remission at 6 months was achieved in 62.3% of cases, with a higher rate in patients with CD than in those with UC. An Asian multicenter study reported that mucosal healing was achieved in less than half of patients with UC within the first year of diagnosis [12].

IBD has a chronic and relapsing clinical course that requires lifelong monitoring and treatment. Furthermore, 13%–46% of patients do not respond or lose response to immunobiologics within 12 weeks of therapy, while approximately 50% of primary responders lose response to maintenance therapy after induction therapy [13]. In our study, more than half of patients responded to treatment within 6 months of initiation, with loss of response in 30%, occurring 12 months after treatment in most cases.

With the increase in therapeutic options, there may be a tendency or desire on the part of the treating physician to rapidly move on to the next therapy and consider the previous therapy a failure. However, this may lead to inadequate optimization of biologic agents and poor disease control. A multicenter study using anti-TNFs reported that the only factor independently associated with primary non-response was low drug concentration at week 14, and combination immunomodulator (thiopurine or methotrexate) therapy reduced the risk of developing anti-drug antibodies [14]. In our study, combination therapy (immunobiologic agent + immunomodulator) was used in 70% of patients; however, optimization was required in less than half of patients.

A Spanish multicenter study concluded that ADA is effective and safe in the management of CD, even in cases refractory to IFX, with no differences between the luminal and perianal phenotypes [15].In our study, there were no statistically significant differences in healing rates between patients with luminal and perianal CD. Furthermore, ADA was the first-line immunobiologic agent in approximately 60% of patients with moderate to severe CD.

Surgical intervention in CD is indicated when conservative treatment is ineffective (refractory) or in the case of complications such as obstructive acute abdomen, ileitis mimicking acute appendicitis, toxic megacolon, bowel perforation, perianal or intra-abdominal abscess (without an adequate window for drainage under imaging guidance), and massive bleeding. In UC, surgery is also indicated for cases refractory to conservative treatment or in the case of complications such as severe acute colitis, toxic megacolon, bleeding with hemodynamic instability, and abdominal sepsis. UC and colonic CD are also associated with an increased risk of colorectal cancer. The 5- and 10- year cumulative risk of colectomy (emergency or elective) is 10%–15% for UC. Due to bowel strictures and/or obstructions, containing varying degrees of inflammation and fibrosis, up to two-thirds of patients with CD will require at least one surgical procedure in their lifetime [16]. In our sample, 10% of patients required surgery, most of them for the treatment of perianal fistulizing disease.

We studied a representative sample of patients with IBD in our state and observed, in line with the literature, the importance of continuous monitoring of the disease from symptomatic relief to endoscopic healing. Furthermore, early personalized therapy, based on the disease phenotype, proved to be an essential element for a favorable outcome, minimizing the risk of complications such as loss of response, change of treatment strategy, and surgical procedures. In our study, endoscopic remission assessed 6 months after initiation of biologic therapy was superior in patients with CD, suggesting that patients with UC have a slower response to treatment.

Institutional review board statement

The study was approved by the Ethics Committee of the Meridional College (Faculdade Meridional, or IMED for short, in Portuguese), Brazil, under protocol number 4.260.203.

Informed consent statement

Written informed consent was obtained from each study participant.

Author contributions

Zabot GP participated in research conduction, statistical analysis, and writing of the text. Feldmann JVM, Bezzi D, and Cassol OS were responsible for data collection and writing of the text. Saad-Hossne R participated in writing and revision of the text.

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3. Cassol OS, Zabot GP, Saad Hossne R, Padoin A. Epidemiology of inflammatory bowel diseases in the state of Rio Grande do Sul, Brazil. World J Gastroenterol. 2022; 28: 4174-4181.

4. Barreiro de Acosta M, Molero A, Artime E, Díaz Cerezo S, Lizán L, de Paz HD, et al. Epidemiological, Clinical, Patient-Reported and Economic Burden of Inflammatory Bowel Disease (Ulcerative colitis and Crohn’s disease) in Spain: A Systematic Review. Adv Ther. 2023; 40: 1975-2014.

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6. Adamina M, Bonovas S, Raine T, Spinelli A, Warusavitarne J, Armuzzi A, et al. ECCO guidelines on therapeutics in crohn’s disease: surgical treatment. J Crohns Colitis. 2020; 14: 155-168.

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Background: Inflammatory bowel diseases, encompassing Crohn’s disease (CD) and ulcerative colitis (UC), are chronic diseases that compromise the gastrointestinal tract due to constant activation of the immune system in response to environmental, genetic, and dietary factors in a genetically susceptible individual. Treatment goals have evolved from simple remission of symptoms to complete mucosal and transmural healing, leading to a change in the choice of treatment strategy from a conventional “step-up” approach to earlier intervention, a rapid step-up approach or even a “top-down” strategy.

Aim: To compare biologic therapy indications and types as well as loss of response rates in patients with UC vs CD.

Methods: We conducted a cross-sectional, observational, open population study by reviewing electronic medical records in a specialized private clinic in Canoas, a city located in Rio Grande do Sul, the southernmost state of Brazil. The sample included all patients aged 18 years or over on follow-up at the clinic since 2016 who agreed to participate in the study by signing an informed consent form. Statistical analysis was performed using Pearson’s chi-square test or Fisher’s exact test. The Z-test was used for multiple comparisons, with Bonferroni correction to compare proportions. Data were analyzed in SPSS, version 25.0. The significance level was set at P<0.05 for all analyses.

Results: A total of 157 patients were investigated, 89 with CD and 68 with UC. Most patients were female, and 68.2% were within the young age range of 20 to 40 years. Regarding CD location, 48% of patients had perianal involvement and 52% had luminal involvement only. Regarding UC extent, 35% had ulcerative proctitis, 41% distal UC, and 24% had extensive UC or pancolitis. Regarding biologic therapy, 72.6% of patients used at least one immunobiologic agent, mostly anti-tumor necrosis factors (80%). In patients using immunobiologics, 62% used only one; 15%, two; 6%, three; and 3%, four. Combination therapy (immunobiologic agent combined with an immunomodulator) was used in 70% of patients. The therapeutic target (endoscopic remission) was achieved in 62.3% of cases, and this rate was significantly higher in patients with CD (72%) than in those with UC (28%). In UC, endoscopic healing was most commonly associated with proctitis (50%), followed by distal UC (36%) and extensive UC (14%). Time to response was <6 months in approximately 58% of patients. Endoscopic healing at 6 months was observed in 70.7% of patients with perianal CD. There were no statistically significant differences in healing rates between patients with perianal and luminal CD. Loss of response was observed in approximately 30% of patients, occurring 12 months after therapy initiation in most cases. Optimization of biologic therapy was required in almost half of patients (49.1%). Approximately 10% of patients required at least one surgical procedure (luminal or perianal).

Conclusion: Early personalized therapy proved essential for favorable outcomes, minimizing loss of response, change of treatment strategy, and surgeries. Endoscopic remission was superior in CD, suggesting a slower response in UC.

• Inflammatory bowel diseases

• Crohn’s disease

• Ulcerative colitis

• Therapeutics

Zabot GP, Feldmann JVM, Bezzi DV, Cassol OS, Saad-Hossne R (2023) Therapeutic Outcomes and Clinical Monitoring in Private Patients with Inflammatory Bowel Disease. JSM Gastroenterol Hepatol 10(3): 1126.

Inflammatory bowel diseases, encompassing Crohn’s disease (CD) and ulcerative colitis (UC), are chronic diseases that compromise the gastrointestinal tract. Early intervention with biologic therapy may prevent progression to irreversible bowel damage. In this study, we analyzed our single-center data of patients with CD and UC between 2016 and 2023, comprising a representative sample of patients with inflammatory bowel diseases in Rio Grande do Sul, the southernmost state of Brazil. Based on these data, early personalized biologic therapy proved essential for favorable outcomes, minimizing the risk of complications such as loss of response, change of treatment strategy, and surgical procedures.

Inflammatory bowel diseases (IBDs), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), are chronic diseases that compromise the gastrointestinal tract due to constant activation of the immune system in response to environmental, genetic, and dietary factors in a genetically susceptible individual [1]. IBDs are more common in Western countries, such as countries in Northern Europe and North America. However, Brazil’s global prevalence has been increasing since 2000, currently affecting 12 to 38 per 100 000 people [2].

Recently, the goals of IBD treatment have evolved from simple remission of symptoms to complete mucosal and transmural healing, leading to a change in the choice of treatment strategy from a conventional “step-up” approach to earlier intervention, a rapid step-up approach or even a “top-down” strategy. This is due to the observation that early treatment with immunobiologics, at the correct stage of the disease, prevents progression to irreversible bowel damage, more commonly observed in patients with CD [1].

This study had the following objectives: 1. To compare indications and types of biologic therapy used in patients with UC vs CD;

2. To detail and characterize secondary loss of response rates, such as dose optimization and medication changes during follow-up;

3. To correlate the use of biologic therapy with disease location and time to mucosal healing by monitoring clinical and endoscopic remission;

4. To evaluate the mean time to dose optimization of biologic agents; 5. To compare time to and characteristics of clinical response between patients with perianal CD and luminal CD only;

6. To analyze the percentage of surgeries performed in this population.

We conducted a cross-sectional, observational, open population study by reviewing electronic medical records in a specialized private clinic in Canoas, a city located in Rio Grande do Sul, the southernmost state of Brazil. The sample included all patients aged 18 years or over on follow-up at the clinic since 2016 who agreed to participate in the study by signing an informed consent form.

The Montreal classification was used for disease phenotyping. The therapeutic target was defined as endoscopic remission, with a Mayo score of 0 for UC and a simple endoscopic score for CD (SES-CD) < 3, assessed 6 months after initiation of biologic therapy. Time to response was defined as the time elapsed between initiation of biologic therapy and remission, assessed through clinical response, biochemistry (C-reactive protein and/ or fecal calprotectin), and ileocolonoscopy combined or not with imaging (computed tomography [CT] enterography or magnetic resonance [MR] enterography). Loss of response was assessed through clinical symptoms and biochemical changes (fecal calprotectin) and confirmed by ileocolonoscopy and/or imaging (CT enterography or MR enterography).

Statistical analysis was performed using Pearson’s chi-square test or Fisher’s exact test. The Z-test was used for multiple comparisons, with Bonferroni correction to compare proportions. Data were analyzed in SPSS, version 25.0. The significance level was set at P < 0.05 for all analyses. The statistical methods of this study were reviewed by Vânia Naomi Hirakata from Hospital de Clínicas de Porto Alegre, Rio Grande do Sul, Brazil.

A total of 157 patients were investigated, 89 with CD and 68 with UC. Most patients were female, and 68.2% were within the young age range of 20 to 40 years (Figure 1). Regarding CD location according to the Montreal classification, 48% of patients with CD had perianal involvement and 52% had luminal involvement only (Montreal L1, L2, and L3). Regarding UC extent according to the Montreal classification, 35% had ulcerative proctitis (E1), 41% had distal UC (E2), and 24% had extensive UC or pancolitis (E3).

Regarding biologic therapy, 72.6% of patients used at least one immunobiologic agent, mostly anti-tumor necrosis factors (anti-TNFs) (80%) (Figure 2). In patients using immunobiologics, 62% used only one; 15%, two; 6%, three; and 3%, four (Figure 3). Regarding time to initiation of biologic therapy after diagnosis, in patients using adalimumab (ADA), 14.0% initiated ADA therapy within 6 months, 17.5% between 6 and 12 months, 17.5% between 12 and 24 months, and 51.0% after 24 months. In patients using infliximab (IFX), 4.7% initiated IFX therapy within 6 months, 20.9% between 6 and 12 months, 14.0% between 12 and 24 months, and 60.4% after 24 months. In patients using ustekinumab (UST), 8.3% initiated UST therapy within 6 months, 20.8% between 6 and 12 months, 37.5% between 12 and 24 months, and 33.4% after 24 months. As for vedolizumab (VDZ), no patient initiated VDZ therapy before 6 months, 25.9% initiated it between 6 and 12 months, 29.6% between 12 and 24 months, and 44.5% after 24 months. Regarding golimumab (GOLI), used only in UC, 11.1% of patients initiated GOLI therapy within 6 months, 66.7% between 6 and 12 months, 22.2% between 12 and 24 months, and no patient initiated it after 24 months. Certolizumab pegol (CTZ) was used in 2 patients with CD: one patient initiated CTZ therapy between 6 and 12 months and the other patient, between 12 and 24 months. Tofacitinib (TOFA), an oral small molecule indicated for UC, was used in only 1 patient, with initiation after 24 months. Combination therapy (immunobiologic agent combined with an immunomodulator) was used in 70% of patients.

Regarding the choice of immunobiologic agent according to disease diagnosis, ADA was used in 59.6% of patients with CD and only 5.9% with UC. IFX was used in 44.9% of patients with CD and 4.4% with UC; UST in 24.7% with CD and 2.9% with UC; and VDZ in 16.9% with CD and 17.6% with UC. GOLI was used in 13.2% of patients with UC. CTZ was used in 2.2% of patients with CD, and TOFA was used in 1.5% of patients with UC. 

The therapeutic target was achieved in 62.3% of cases (Figure 4). The rate of endoscopic remission at 6 months was significantly higher in patients with CD (72%) than in those with UC (28%) (P < 0.001) (Figure 5). In UC, endoscopic healing was most commonly associated with Montreal disease extent E1 (proctitis), accounting for 50% of patients, followed by E2 (distal UC) in 36% and E3 (extensive UC) in 14% (Figure 6).

Time to response was < 6 months in approximately 58% of patients, 6–12 months in 24%, and > 12 months in 11%; 7% were primary non-responders (Figure 7). Endoscopic healing at 6 months was observed in 70.7% of patients with perianal CD (Figure 8). There were no statistically significant differences in healing rates between patients with CD with perianal involvement and luminal involvement only (Figure 9).

Loss of response was observed in approximately 30% of patients, occurring 12 months after therapy initiation in most cases (Figure 10). Optimization of biologic therapy was required in almost half of patients (49.1%), occurring in < 6 months in 18%, between 6 and 12 months in 20%, between 12 and 24 months in 20%, and in > 24 months in 42% (Figure 11).

Approximately 10% of patients required at least one surgical procedure (luminal or perianal), which was performed in < 6 months in 31.3%, between 6 and 12 months in 25.0%, between 12 and 24 months in 6.3%, and in > 24 months in 37.4% (Figure 12).