Clinical Case Summary

Psoriasis and Inflammatory Bowel Disease (IBD) overlap in epidemiology and immune mechanisms. Biologics have been used to treat both conditions. Interleukin-17 inhibitors (anti-IL-17) play a vital role in the approach of refractory psoriasis, but paradoxal gastrointestinal effects may occur.
A 67-year-old woman with chronic plaque psoriasis and arthritis refractory to methotrexate (MTX) and ustekinumab, at that moment under Ixekizumab (anti-IL-17), presented to the emergency room with chronic abdominal pain, diarrhea (>10 bowel movements/day) and rectal bleeding. Blood workup showed normocytic normochromic anemia (9,9g/dL) and elevated C-reactive protein (181mg/L). Clostridioides difficile toxin test and stool cultures were negative. Computed tomography showed sigmoid colon and rectum wall thickening and densification of the surrounding fat. Endoscopy revealed deep ulcers in the rectum and sigmoid.
The main diagnostic hypothesis were severe inflammatory proctocolitis triggered by anti-IL-17 and infectious colitis (including cytomegalovirus (CMV) infection). Clinical, endoscopic and histopathologic findings supported a Crohn’s-like colitis possibly triggered by Ixekizumab. Histopathology revealed chronic inflammation and excluded CMV infection.
Ixekizumab was discontinued; clinical remission was induced with Infliximab (IFX), after corticosteroid (CT) failure. Six weeks later, she was admitted with cellulitis. CT was rapidly tapered. Due to her medical background as well as clinical, biologic and endoscopic improvement, after a multidisciplinary discussion, it was decided to maintain IFX in association with MTX. Further follow-up revealed clinical remission and endoscopic response.
The increasing use of anti-IL-17 in psoriatic patients led to the report of rare cases of IBD onset in this population. This case suggests a possible association between anti-IL-17 therapies and de novo IBD, highlighting the need of surveillance of patients under these therapies.

References

Endoscopic images (total of 4 pictures); photographs of lower limbs (total of 5 pictures).

Introduction

Since their introduction, biologics have drastically improved management of clinical symptoms in patients with inflammatory bowel disease (IBD); however, historically, biologics have been very expensive medications. Biosimilars provide similar clinical efficacy and safety to reference product (RP) biologics at a reduced cost, which has helped to alleviate undue strain on the healthcare system and improve patient access to biologics treatment. Despite these advantages, uptake remains slow in some regions, which may be due to limited awareness among patients and clinicians. This review sought to understand the recommendations for biosimilar use from government agencies and clinical societies, as they can be an important source for education

Aims & Methods

A literature search was conducted in MEDLINE and Google Scholar focusing on the use of biosimilars in gastroenterology. Search terms included biosimilar and gastroenterology, in combination with position, guidance, recommendation, workshop, or consortium. The literature search was restricted from 2006 (time of biosimilar approval) to present.

Results

Following screening there were 20 position statements/guidelines identified. The use of biosimilars was discussed among gastroenterology societies in Belgium (n = 2), Brazil (n = 1), Canada (n = 2), Italy (n = 2), Korea (n = 2), Mexico (n = 1), Poland (n = 2), Spain (n = 1), and the USA (n = 1) with regional representation from Europe (eg, ECCO) and Asia (n =2). Five were published before 2015 and 15 were published in 2015 or later. Although government agencies such as the European Medicines Agency and Food & Drug Administration published positive recommendations for the use of biosimilars, statements from key clinical societies from Canada, Europe, Italy, Poland, and Spain expressed concerns regarding the use of biosimilars for patients with IBD in the early 2010s. The main objection was the extrapolation of biosimilar indications to IBD from clinical studies in patients with rheumatoid arthritis, as statements suggested that clinical trials of biosimilars specific to IBD were necessary before their use. Since then, the efficacy and safety data from real-world observational studies, and the acceptance of indication extrapolation have contributed to positive recommendations from most clinical societies regarding biosimilar use. For example, 2014 guidelines published in Poland was not supportive of biosimilars; however, updated guidelines in 2019 noted that approved biosimilars were not significantly different from originator medicines. Most clinical societies approve biosimilar use for patients with IBD naïve to the molecule as well as those with stable disease, switching from the RP medicine to the biosimilar. One notable exception to this trend is a 2020 Canadian position statement recommending against nonmedical switching from originator to biosimilar in patients with stable IBD. However, several Canadian provinces have since adopted policies that support nonmedical switching, suggesting that medical practices and future Canadian position statements may change.

Conclusion

As real-world efficacy and safety studies continue to demonstrate the clinical value of biosimilars, perceptions surrounding their use have greatly improved among several key clinical societies globally. Notably, most societies expressed the importance of patient consent when deciding to switch to biosimilars. Thus, services that provide education to patients to increase awareness of and confidence in biosimilars are critical to ensure their use and should be optimized to promote expanded patient access.

Disclosure

Kunal Shastri is an employee of Fresenius Kabi, a manufacturer of biosimilars. Kerise Clarke, Margaret Ainslie-Garcia, and Nicole Ferko are employees of EVERSANA who receives consulting fees from Fresenius Kabi.

Introduction

Segmental colitis associated with diverticulosis (SCAD) is an increasingly recognized clinical and pathological disorder, characterized by a chronic inflammatory response involving the inter-diverticular mucosa of a colonic segment, sparing the rectum and the right colon. However, its prevalence and outcome in the setting of colorectal cancer (CRC) screening is unknown.

Aims & Methods

Aims: to assess the prevalence of SCAD in the setting of a CRC screening program and to evaluate the differences in terms of oncological outcomes between SCAD and "simple" diverticulosis. We performed a retrospective analysis from a prospectively-maintained database including all subjects undergoing first screening colonoscopy according to regional CRC program from 2019 to 2022. Patients with incomplete colonoscopy, inadequate bowel preparation or known diagnosis of SCAD or CRC were excluded. Endoscopic signs of SCAD were registered as “crescentic fold disease”, “mild-to-moderate UC-like”, “Crohn’s disease-like” and “Severe UC-like”. The number of adenomas (ADR) and cancers was also recorded. Statistical analysis included chi-square, Student’s t-test and odds ratio (OR) with 95% confidence interval (CI) when indicated.

Results

a total of 1518 patients were included (males 51.8%, mean age 63.48±6.39). Adenomas were detected in 638 patients (ADR 42%), while CRC was diagnosed in 86 cases (5.7%). Diverticulosis was described in 570/1518 patients (37.5%), while SCAD was endoscopically diagnosed in 69 patients (4.5%). Among them, 48 (69.6%) presented a crescentic fold disease, 14 (20.3%) a mild-to-moderate UC-like pattern, 6 (8.7%) a CD-like pattern and 1 (1.4%) had a severe UC-like pattern. When SCAD patients were compared to subjects with simple diverticulosis (501 patients), we found no differences in terms of gender (males 55.1% vs 50.7%, p=0.46) or age (63.86±6.45 vs 64.45±6.38, p=0.47). Interestingly, the use of anticoagulant/antiplatelet (28.9% vs 30.1%, p=0.79), anti-hypertensive (46.4% vs 48.1%, p=0.89) or anti-hyperglycemic drugs (36.2% vs 41.1%, p=0.52) had no effect on SCAD onset as compared with patients with diverticulosis. However, patients with SCAD had significant lower rate of adenomas (ADR 31.9% vs 47.3%, p=0.018, OR 0.52, 95%CI 0.31-0.89), and lower –but not significant– rate of CRC (1.4% vs 6.2%, p=0.14, OR 0.22, 95%CI 0.02-1.66). Most patients were successfully treated with 5-ASA and none needed surgery for SCAD.

Conclusion

SCAD can be diagnosed in about 5% of population undergoing screening colonoscopy and in about 12% of those with diverticulosis. SCAD seems to be associated with a reduced rate of adenomas or CRC as compared with diverticulosis.