Abstract
There exists a significant care gap in the diagnosis, treatment, and management of inflammatory bowel diseases (IBD) in Latin America compared to the United States and Europe. This review aims to assess the clinical effectiveness of advanced therapies for patients with moderate to severe ulcerative colitis (UC) and Crohn’s disease (CD) in Latin America. We conducted a targeted literature review of studies reporting clinical outcomes of advanced IBD therapies in Latin American countries. After applying pre-defined inclusion and exclusion criteria, 14 articles were included. Data were extracted regarding patient populations, therapeutic agents, clinical outcomes, and geographic distribution. The majority of studies focused on biologic therapies, including adalimumab, infliximab, ustekinumab, and vedolizumab. These therapies demonstrated favorable clinical remission and response rates in Brazil, Argentina, Mexico, and Colombia for both UC and CD. Reported outcomes were largely consistent with observational data from North America and Europe, supporting the generalizability of therapeutic efficacy across regions. Advanced therapies for IBD appear to be effective in Latin American populations, with clinical outcomes comparable to those reported globally. Increasing access to these treatments may improve patient outcomes, reduce disease burden, and potentially decrease long-term healthcare costs in the region.
Background
Inflammatory bowel disease (IBD) is the designation provided to two diseases caused by inflammation of the colon and/or the small intestine: Crohn’s disease (CD) and ulcerative colitis (UC). CD most commonly affects the ileum and colon, but it can sporadically involve any part of the intestine. UC involves the rectum and may affect additional portions of the colon in a continuous pattern. In CD, inflammation is frequently transmural. However, in UC, inflammation is typically limited to the mucosa. 1 The Latin American Clinical Guidelines state that patients with UC and CD should initiate treatment with conventional therapies such as 5-aminosalicylates (5-ASA) and corticosteroids. 2
Patients not responding to these conventional therapies and displaying signs of moderate to severe disease should initiate treatment with advanced therapies. These include biologics and small molecules, such as Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators. 3 The introduction of advanced therapies (biologics and small molecules) has drastically changed how IBD is managed, offering patients who are unresponsive to corticosteroids and 5-ASAs effective alternatives. These include adalimumab (ADA), certolizumab, etrasimod, golimumab, infliximab (IFX), ozanimod, risankizumab, tofacitinib, upadacitinib, ustekinumab (UST), and vedolizumab (VEDO). Newly approved therapies such as ozanimod, risankizumab, mirikizumab, and upadacitinib will be available in Latin America in the near future. 4
The incidence of IBD in Latin America has increased over recent years. A Brazilian study identified an increase in combined IBD prevalence from 1.2 to 21 per 100,000 inhabitants over 24 years (1988–2012). 5 Another literature review reported that the incidence (reported per 100,000 person-years) of CD in Brazil increased from 0.68 in 1991–1995 to 3.50 in 2001–2005, reaching an incidence of 5.48 in 2015. Also, from 1991–1995 to 2001–2005, UC incidence rose from 3.86 to 5.3, with a highest rate of 8.00 in 2015. 6 The prevalence of IBD also steadily rose in Latin America. For example, the prevalence of CD in Brazil rose from 0.24 per 100,000 persons (1986–1990) to 24.1 (2014). The prevalence of UC rose from 0.99 to 14.1 in the same period. The prevalence of IBD per 100,000 people was also high in Argentina (97.2), Colombia (57.62 in 2012), and Puerto Rico (38.22 in 2005). 6 The use of biologics in Latin America is lower compared to other regions, due to gaps in knowledge regarding their use and monitoring, as well as barriers to access. 2 The vast majority of patients are diagnosed late due to a combination of factors, such as self-medication or the lack of training of some primary care physicians, which delays referral to a specialist for diagnosis. 2
A recent survey of IBD physicians in Latin America documented that access to advanced IBD therapies was “very difficult” in Argentina, Bolivia, Paraguay, and Venezuela. Access was “somewhat difficult” in Mexico, Chile, and Ecuador. 4 Physicians from the south of Brazil also reported difficulty obtaining biologics. 7 Due to limited access to advanced therapies in Latin America, patient outcomes are worse compared to higher-income nations. The complication rate (defined as UC-related hospitalization, rectum or intestinal surgeries, and/or malignant neoplasia of colon, stenosis, hemorrhage, megacolon, functional diarrhea volvulus, intussusception, and erythema nodosum) among patients with UC undergoing therapy available in the Brazil National Health System from 2011 to 2020 was higher among those receiving only conventional therapy, 8 and availability of advanced therapies was extremely limited, especially within the public health system. 7
Based on the disparities observed with respect to clinical outcomes, we conducted a targeted literature review evaluating the use of advanced therapies in Latin America and their clinical impact. This information may provide more insights into the value of increasing advanced IBD therapy access and utilization in the region.
Methods
A literature search was conducted using the PubMed international database, EMBASE international database, and SciELO, a Latin American/Caribbean/Spanish database. Three search statements were used in each database: “IBD Drug Therapy in Central America,” “IBD Drug Therapy in South America,” and “IBD Drug Therapy in Latin America.” However, as this may result in the potential to miss relevant articles, an additional 66 searches in each of the three databases were conducted. These searches included using a combination of the following search terms: Full names of the following advanced therapies: ADA, certolizumab, etrasimod, golimumab, IFX, ozanimod, risankizumab, tofacitinib, upadacitinib, UST, and VEDO, and “Ulcerative Colitis” or “Crohn’s Disease” and “South America” or “Central America” or “Latin America.” A total of 207 searches were conducted [(3 × 3) + (66 × 3)]. No language or time restriction was placed.
A total of 1285 abstracts were found based on the search criteria. Studies included multicenter retrospective observational cohort studies, cross-sectional studies, retrospective medical chart reviews, and open-label prospective clinical trials with only Latin American patients.
We excluded studies focusing solely on pediatric populations, US Hispanic populations, expert opinions, surveys, meta-analyses, case studies, infectious complications of IBD, and surgical outcomes only. We also excluded global studies with no data on Latin American subgroups, articles lacking advanced therapy treatment outcomes, articles displaying drug concentration data with patients in remission, cancer-related outcomes, biosimilar-related outcomes, and articles not published in English. After applying our exclusion criteria as shown in Figure 1, 14 relevant articles were included in the review. The proportion of patients among different categories of baseline disease severity (mild, moderate, or severe) in UC and CD was also calculated for each Latin American country, using studies where this information was reported.
Identification of studies.
Results
Fourteen articles documented response rates of advanced IBD therapies in Brazil, Colombia, Mexico, and Argentina. The advanced therapies studied included IFX, ADA, tofacitinib, UST, VEDO, golimumab, and certolizumab. Table 1 summarizes the characteristics and clinical outcomes of each of the included 14 studies. The extracted data from these articles included study characteristics (author, year, country, study design), participant information (mean age, sex, type of IBD, baseline severity), details of advanced therapy treatment (type of drug, duration), and clinical outcomes (clinical remission, suboptimal response, and clinical response).
Characteristics and outcomes of included studies.
ADA, adalimumab; CD, Crohn’s disease; CDAI, Crohn’s disease activity index; HBI, Harvey–Bradshaw index; IBD, inflammatory bowel disease; IFX, infliximab; LOCF, last observation carried forward; NRI, non-responder imputation; PGA, physician global assessment; UC, ulcerative colitis; UST, ustekinumab; VEDO, vedolizumab.
Baseline severity of disease in the included studies was defined using endoscopy severity12–15 and clinical disease activity scores.10,16–18 The distribution of UC baseline severity status in Brazil was 12.6% with mild disease, 66.7% with moderate disease, and 20.8% with severe disease. Similarly, the distribution in Colombia was 1.7% (mild), 41.4% (moderate), and 56.9% (severe). Argentina had 6.7% (mild), 33.3% (moderate), and 60% (severe). Finally, Mexico had 22.2% (mild), 38.9% (moderate), and 38.9% (severe).
The distribution of CD baseline severity status in Brazil was 34.8% mild, 65.2% moderate, and 0% severe. In Colombia, all patients were diagnosed with mild disease. In Argentina, the distribution was 15.6% (mild), 46.9% (moderate), and 37.5% (severe). Finally, the distribution in Mexico was 57.1% (mild), 42.9% (moderate), and 0% (severe).
Detailed clinical outcomes are reported in Table 1. Ten of the 14 included studies reported clinical remission rates of advanced therapies in Brazil.9,11–14,16,17,19–21 These studies evaluated IFX, ADA, tofacitinib, UST, VEDO, and certolizumab. Five studies presented results for CD,11,17,19–21 four studies evaluated UC patients,12–14,16 and one study had a mix of UC and CD patients. 9 Clinical remission rates for UC at week 12 ranged from 18% 14 to 68.3%. 16 Clinical remission rates for UC at week 52 ranged from 18.4% 9 to 65.2%. 16 Clinical remission rates for CD at week 12 ranged from 42.9% 9 to 80%. 19 Clinical remission rates for CD at week 52 ranged from 46.1% 9 to 88.1%. 17
Three studies reported clinical remission rates in Colombia.10,15,18,22 Two evaluated IFX in UC 15 and VEDO in UC and CD patients. 10 The third study analyzed outcomes by line of therapy in UC and CD and included multiple agents (IFX, ADA, VEDO, golimumab, UST, tofacitinib, and certolizumab). 22 Clinical remission rates for UC at week 12 ranged from 62.5% 10 to 79.2%. 15 Clinical remission rates for UC at week 52 ranged from 47.6% 15 to 75%. 10 Clinical remission rates for CD at week 12 ranged from 19.4% 22 to 80%. 10 Clinical remission rates for CD at week 52 ranged from 16.7% 22 to 80%. 10
One study evaluated only suboptimal response by lines of therapy (IFX, ADA, and golimumab in UC and ADA, IFX, and certolizumab in CD) in Argentina, Colombia, and Mexico. 18 In Argentina, the suboptimal response to anti-TNF therapy in UC was 30% at 12 months and 44.5% at 24 months, and in CD was 37.9% at 12 months and 49.2% at 24 months. In Colombia, the suboptimal response to first-line anti-TNF therapy in UC was 50% at 12 months and 68.8% at 24 months, and in CD was 36% at 12 months and 49.7% at 24 months. In Mexico, the suboptimal response to anti-TNF therapy in UC was 8.3% at 12 months and 14.9% at 24 months, and in CD was 16.1% at 12 months and 20.6% at 24 months.
Discussion
Latin American patients have faced challenges in accessing IBD therapies due to high costs, insufficient insurance coverage, and a lack of specialized GI centers.7,23 We believe our review is the first to summarize the use of advanced therapies in Latin America. We hope these data will help regional healthcare policymakers understand the importance of utilizing advanced IBD therapies to reduce morbidity, improve quality of life, and increase work productivity in patients with IBD. Since many branded advanced therapies have or will have lower-cost biosimilar options available, access will likely improve. It is increasingly important that advanced therapies with different mechanisms of action are strategically used within IBD care in Latin America to maximize the likelihood of favorable patient outcomes.
After examining the 14 studies included in this review, baseline severity of patients across all Latin American countries, as reported in the results, was not evenly split between mild, moderate, and severe disease categories of IBD. Data from Colombia and Mexico reported the highest proportion of severe patients and mild patients at baseline, respectively. Our literature review found that despite variability in baseline disease severity, advanced IBD therapies within Latin America demonstrated strong effectiveness, with nearly half of patients achieving clinical remission at week 52 in the majority of studies. These results are comparable to large observational studies or systematic literature reviews of real-world data outside of Latin America, as shown in Table 2.
Clinical outcomes to select advanced therapies in countries across multiple regions.
CD, Crohn’s disease; IBD, inflammatory bowel disease; UC, ulcerative colitis.
ADA demonstrated high clinical remission rates in Brazilian UC patients,11,19 similar to observational studies for ADA in Italy 24 and Japan. 25 The clinical remission rates of IFX in Brazil also aligned with outcomes from real-world observational studies in France 26 and Italy. 30 In Brazil, both ADA and IFX were well-tolerated, and early response was found to be a predictive factor for higher long-term remission rates. 16 These results also provide an indication of long-term benefits to the healthcare system, as treatment with advanced therapies leads to reduced hospitalizations and surgeries over time. 31
The clinical remission rates of UST in Brazilian IBD patients14,21 were also comparable to a U.S. multicenter real-world study. 27 The unique mechanism of action of UST could be a valuable alternative in Latin America for patients who are not controlled using other drugs, such as anti-TNF therapies. Additional studies of UST that include a greater number of patients with a longer follow-up duration are needed in Latin America. The clinical remission rates of VEDO in Brazilian9,17 and Colombian IBD patients were consistent with a recent global meta-analysis of real-world studies. 28 The research conducted with VEDO in both Brazil and Colombia primarily included patients refractory to anti-TNF therapies. Despite this, VEDO proved to be clinically effective with good safety outcomes.
Latin American IBD patients tend to utilize high quantities of steroids as opposed to advanced therapies. 32 The current study findings highlight the importance of expanding access to advanced therapies, especially considering the potential harms associated with excessive use of corticosteroids. Chronic steroid use in IBD management has been linked to serious side effects, including osteoporosis, hypertension, and increased infection risk. 33 Chronic steroid use is also associated with the need for primary surgery and reoperation. Despite these risks, a significant portion of patients with IBD are overusing or dependent on steroids.34,35 Therefore, timely escalation to more targeted biologics or advanced therapies is essential not only for disease control but also for minimizing long-term treatment-related complications.
Investment in the utilization of advanced therapies may lower the overall healthcare costs associated with IBD in the region. This could occur with the use of cheaper biosimilar options of advanced therapies, which are increasing in availability. Due to the equivalence in clinical efficacy of biosimilar therapies to their originators, their use would be expected to minimize corticosteroid exposure and reduce IBD complications, such as surgeries and hospitalizations. This may, in turn, reduce expenditures. 36
This review has several limitations. Findings are presented descriptively, and no meta-analytic techniques were used due to the small sample sizes. Many of the included studies evaluated clinical outcomes within specific regions, which may not be generalizable to the entire country. Also, definitions of clinical remission and response and doses of therapy differed between studies. Patient characteristics also varied widely between studies, especially with respect to treatment experience. Studies included were also not randomized or blinded and therefore causality between treatment and response cannot be established. Adherence to treatment may not be as rigorous as clinical trials, but the included studies are more likely to reflect real-world clinical practice. The sample size observed in some of the categories was extremely small, and disease severity definitions varied between studies, which made statistical comparisons inappropriate. In addition, the possibility of publication bias must be acknowledged, as studies with positive outcomes are more likely to be published than those with negative and inconclusive results. Relevant findings from gray literature, including conference abstracts or unpublished reports, may also be underrepresented. Furthermore, the exclusion of non-English studies introduces the possibility for language bias, which may limit the comprehensiveness and inclusivity of the evidence. While 15 studies were published in Spanish or Portuguese, all of them had corresponding abstracts available in English that were screened; however, none of these met the inclusion criteria due to a lack of clinical outcome data specific to advanced therapies. Therefore, the exclusion of these studies is unlikely to bias the findings of this review.
Future research in Latin America should explore changes in access to IBD care, treatment adherence, and patient/provider preferences for different treatment routes and delivery of care options. Also, due to the limited data available, additional research should be conducted to evaluate therapies outside of the anti-TNF class. More studies evaluating long-term benefits of IBD treatments to the overall healthcare system and cost-effectiveness are warranted. Research must also consider cultural, economic, and logistical factors that affect patients’ access to these therapies, with a focus on disparities in rural versus urban settings. Consideration also needs to be given to patient characteristics, safety profile, speed of onset, and route of administration.
This targeted literature review aimed to assess the clinical effectiveness of advanced therapies in the treatment of IBD in Latin America. Despite regional disparities in access and treatment availability, the studies reviewed consistently demonstrated that advanced therapies, including anti-TNF agents, integrin antagonists, IL-12/23 inhibitors, and small molecules, are effective and well-tolerated in real-world settings across Brazil, Colombia, Argentina, and Mexico. The clinical remission and response rates observed are comparable to those reported in North America and Europe, reinforcing the value of these treatment options. These findings highlight the urgent need to expand access to advanced IBD treatments in Latin America, as doing so holds the potential to improve patient outcomes, reduce complications, and relieve the economic stress on regional healthcare systems. Expanding access to and the use of these therapies is critical for closing the existing care gap and ensuring more effective, long-term disease control for patients with IBD in Latin America.
Footnotes
Acknowledgements
None.
Author’s note
Summary of articles’ main point: This literature review found that advanced IBD therapies utilized in Latin America demonstrated strong effectiveness in terms of clinical and endoscopic remission. These results are comparable to observational studies and systematic literature reviews of real-world data outside of Latin America.
