Real world practice of medical treatment for moderate and severe inflammatory bowel diseases in Russian Federation, Republic of Belarus and Republic of Kazakhstan: intermediate results of the INTENT study

Abstract

Background: The analysis of data obtained from real world clinical practice of management of patients with inflammatory bowel diseases (IBD) is an effective tool to improve medical care for this patient category. Studies of the kind are rare in Russia, which hinders a critical assessment of the current situation and optimization of the established approaches.Aim: To study real world practice of medical treatment of patients with moderate and severe IBD in the Russian Federation, Republic of Belarus and Republic of Kazakhstan.Materials and methods: We analyzed intermediate results from the INTENT study (NCT03532932), which is a multinational, multicenter, retrospective and prospective, non-interventional observation trial being performed in the Russian Federation, Republic of Belarus and Republic of Kazakhstan. The retrospective analysis included data from 706 patients above 18 years of age with confirmed diagnosis of moderate/severe ulcerative colitis (UC) and Crohn's disease (CD) made at least 2 years before the study entry, with acute exacerbations of the disease at the study entry or within the last 2 years. Data were collected during routine management; at the study entry the patients were treated with a standard regimen including 5-aminosalicylic acid (5-ASA) agents, glucocorticosteroids (GCS) and immunosuppressants (IS), as well as genetically engineered biological agents (GEBA).Results: Among 706 IBD patients, 465 had UC and 241 had CD. The male to female ratios in both groups were similar. Mean age of the UC patients was higher than that of the CD patients (41.8 [95% confidence interval (CI) 40.6–43.0] years vs 35.6 [95% CI 33.9–37.3] years, p = 0.0001). The same difference was noted for the mean age of disease manifestation (34.5 [95% CI 33.29–35.61] vs 29.7 [95% CI 28.03–31.3] years, p = 0.0001) and for mean duration of disease from the time of diagnosis to the study entry (7.3 [95% CI 6.77–7.9] for UC and 5.9 [95% CI 5.3–6.59] years for CD, p = 0.0027). The proportion of patients with familial history of IBD was low (3.2 and 0.8%, respectively, p = 0.0672). The number of smokers with CD was more than 2-fold higher than those with UC (11.2% vs 5%, p < 0.001). 58.1% of the patients in the UC group and 47.0% of those from the CD group were employed (р < 0.05). 36.6% of the UC patients and 56.0% of the CD patients had the legal disability status due to underlying disease (p < 0.005). The relapsing course of the disease was noted in 72.9% with UC and 60.6% with CD, while in the rest of the patients the disease had the continuous course. The degree of UC involvement corresponded to pancolitis in 58.9% of the cases, to left-sided colitis in 33.1%, and to proctitis in 8%. The distribution of CD location was as follows: ileocolitis 54.8%, terminal ileitis 23.7%, colitis 20.3%, isolated upper gastrointestinal tract involvement 1.2%. The prevalence of complicated UC was 12.9%, and that of the complicated CD 57.4% (р = 0.0001). There were no difference in the rate of extraintestinal manifestations between UC and CD (23.4 and 28.2%, respectively, p = 0.1705). UC and CD groups differed by their treatment patterns. In the UC group, 5-ASA + GCS regimens were given to 25.4% of the patients, whereas in the CD group, to 3.7% (р ≤ 0.0001). The second frequent regimens were: 5-ASA with subsequent IS ± GCS (17.9% in UC, 22.8% in CD, p = 0.1331); standard regimen (any 5-ASA agent, IS or GCS, but not GEBA) with subsequent treatment withdrawal or its reduction to GCS monotherapy (14.8% in UC, 5% in CD, р = 0.0001); 5-ASA with a subsequent combination with IS, then any tumor necrosis factor-α inhibitor (iTNF-α) as the basic treatment with continuation of 5-ASA and/or IS (22% in CD vs 13.5% in UC, р = 0.0052); treatment initiation from iTNF-α combined with any standard agent without any subsequent modification (24.1% in CD and 13.6% in UC, р = 0.0007). Less frequent the following treatment regimens were used: initial treatment with 5-ASA and subsequent iTNF-α with continuation of 5-ASA (4.5% in UC and 2.5% in CD, р = 0.2181); initial treatment with iTNF-α in combination with any standard agent with subsequent GEBA withdrawal and continuation of a standard regimen or its withdrawal (4.3% in UC and 7.5% in CD, р = 0.0812). The cumulative frequency of GEBA administration at various stages of treatment for CD (66.4%) was significantly higher than for UC (39.4%). Vedolizumab for CD was administered more frequently than for UC (10.4 and 3.4%, respectively, p = 0.0003). The analysis of habitual GCS use revealed a number of negative trends, namely, half of the IBD patients received more than 2 GCS courses within 2 years, and in some cases the number of GCS courses amounted to 5–8. Mean duration of a GCS course in most regimens for UC and CD was in the range of 91 to 209 days, which is significantly higher than the recommended treatment duration of 12 weeks (83 days).Conclusion: With a number of its demographic characteristics and clinical particulars, the study cohort of patients with IBD is compatible to global trends: the male to female ratio, mean patients’ age, young age at disease manifestation, smoking status, prevalence of extraintestinal manifestations and the location of CD. It is of note that 5-ASA is included into almost all treatment regimens for CD, which does not meet the treatment strategy recommended in the guidelines. Frequent administration and long duration of GCS therapy also is in contradiction with the guidelines. Of significant concern is rather rare and late administration of GEBA, especially for UC. We believe that the identified pitfalls are associated both with low awareness of doctors on the current strategies of IBD management and with low patients' compliance to treatment.