In a recent study published in Scientific Reports, researchers compared changes in inflammatory bowel disease (IBD) treatment strategies before and after the introduction of biologics in Japan.
IBD is a chronic, obstinate gastrointestinal condition with recurring relapses and remissions. It requires aggressive therapy.
In Japan, IBD has recently changed from a rare illness treated solely in specialist hospitals to a common condition found in general hospitals. Many molecular targeted agents, including biologics, have widened the therapeutic landscape of IBD; however, their high expense prevents their extensive usage.
Moreover, the use of molecular targeted agents depends on the individual’s medical environment, and information on the most appropriate treatment for individuals with refractory IBD is scarce.
About the study
In the present study, researchers described the characteristics and treatment strategies before and after biologics implementation in Japanese clinical practice by performing data mining.
Data were analyzed from the multicenter prospective “Far East 1000” study on Japanese IBD patients enrolled between January and September 2019. The study included five IBD expert-type and ten non-expert Japanese hospitals. Individuals were categorized based on the IBD diagnosis year and infliximab treatment into the pre-biologic and biologic era groups.
Individuals who received a Crohn’s disease (CD) diagnosis on or after 2002 or an Ulcerative Colitis (UC) diagnosis on or after 2010 formed the biologic era group, whereas those diagnosed with IBD before the biologic era group formed the pre-biologic era group. Association analyses were performed to evaluate the evolution of IBD therapeutic strategies and the impact of medication histories on specific drug selection.
Data were obtained on gender, age at IBD onset and enrollment, IBD distribution, smoking habits, IBD severity, laboratory reports, endoscopy results, and medication history. IBD severity was assessed using the clinical disease activity index for CD and the Lichtiger index for UC patients. Endoscopy findings were analyzed using the simple-endoscopic score (SES) for CD and Mayo endoscopic scores for UC patients. IBD therapy was administered based on evidence-based practice recommendations in Japan. Medications were selected based on IBD severity and response to corticosteroid treatment for CD and UC.
In total, 186 and 542 patients with Crohn’s disease and ulcerative colitis, respectively, were analyzed. Among biologic-era individuals, the age at disease diagnosis was considerably higher than pre-biologic-era individuals (ulcerative colitis: 34 years versus 39 years; Crohn’s disease diagnosis: 24 years versus 32 years).
The percentages of individuals who received IBD diagnosis in the pre-biologic and biologic eras were 47% and 53% for UC and 24% and 76% for CD, respectively.
Among the participants, 165 (30%) UC patients and 24 (13%) CD patients were treated at non-specialist community hospitals, whereas 162 (87%) CD patients and 377 (70%) UC patients received treatment at specialist hospitals. Biologics and immunomodulator drugs were predominantly medicated at expert hospitals for CD and UC patients.
Association analysis performed for individuals with polypharmacy histories showed that the pre-biologic era group individuals preferred agents against tumor necrosis factor-alpha (TNF-α), such as Adalimumab and Infliximab, whereas the biologic era group individuals selected other biologic medications with different molecular mechanisms.
Molecular agents such as Janus kinase (JAK) inhibitors were more frequently used among biologic era group participants in spite of the shorter duration of therapy (22% and 32% in the pre-biologic and biologic era groups, respectively).
Among small molecule and biologic medications, the biologic era group participants showed an increased likelihood of being administered new therapies, such as tofacitinib (TOF), golimumab (GLM), and vedolizumab (VED). The pre-biologic group showed an increased likelihood of receiving conventional treatments such as apheresis.
Among UC patients consuming multiple medications, GLM and VED were the preferred drugs in the pre-biologic and biologic era groups, respectively. VED preference among biologic-era individuals could be related to the recent increases in UC prevalence rates with older onset since vedolizumab does not lead to immunosuppression and is regarded safe for use among older individuals.
Adalimumab formed clusters with high lift values among pre-biologic era group individuals, and Ustekinumab (UST) was preferred with high lift values among biologic era group individuals when assessing the discrepancies in drug combinations between the groups.
Most IBD patients with CD and UC onset between the 1970s and 1990s developed IBD at a young age, but those with older onset increased from 2000 onwards. The team found significantly positive associations between the year of IBD onset and age at diagnosis for ulcerative colitis and Chron’s disease, respectively.
Non-experts mostly managed easy ulcerative colitis cases that would resolve with corticosteroid and 5-Aminosalicylic acid (5-ASA) therapies, whereas most CD cases, including steroid-dependent and steroid-resistant cases, with biologic or immunomodulator administration were mainly managed at specialist hospitals.
Overall, the study findings highlighted changes in therapy preferences among IBD patients after the implementation of biologics.
The findings might reveal patients’ and physicians’ treatment choices in the real world due to the distinct Japanese subsidy system, which enables almost free collaborations, and recruitment and training of IBD experts are needed to bridge the knowledge gap between expert and non-expert hospitals.
Ustekinumab might be preferred for situations occurring after using anti-tumor necrosis factor-alpha medications.