Effectiveness and Safety of Nonmedical Switch From Adalimumab Originator to SB5 Biosimilar in Patients With Inflammatory Bowel Diseases: Twelve-Month Follow-Up From the TABLET Registry.

BACKGROUND: Few data are currently available about SB5 in inflammatory bowel diseases (IBD). The aim of this study was to assess the effectiveness and safety of SB5 in a cohort of patients with IBD in stable remission switched from the adalimumab (ADA) originator and in a cohort of patients with IBD naïve to ADA. METHODS: We prospectively enrolled patients with IBD who started ADA treatment with SB5 (naïve cohort) and those who underwent a nonmedical switch from the ADA originator to SB5 (switching cohort). Clinical remission and safety were assessed at baseline and at 3, 6, and 12 months. In addition, in a small cohort of patients who were switched, we assessed the ADA serum trough levels and antidrug antibodies at baseline, 3, and 6 months. RESULTS: In the naïve cohort, the overall remission rate at 12 months was 60.42%, whereas in the switching cohort it was 89.02%. Fifty-three (36.3%) patients experienced an adverse event, and injection site pain was the most common; it was significantly more frequent in the switching cohort (P = 0.001). No differences were found in terms of ADA serum trough levels at baseline, 3, and 6 months after switching. No patient developed antidrug antibodies after the switch. CONCLUSIONS: We found that SB5 seemed effective and safe in IBD, both in the naïve cohort and in the switching cohort. Further studies are needed to confirm these data in terms of mucosal healing.

The use of 5-aminosalicylate for patients with Crohn's disease in a prospective European inception cohort with 5 years follow-up - an Epi-IBD study.

BACKGROUND: The lack of scientific evidence regarding the effectiveness of 5-aminosalicylate in patients with Crohn's disease is in sharp contrast to its widespread use in clinical practice. AIMS: The aim of the study was to investigate the use of 5-aminosalicylate in patients with Crohn's disease as well as the disease course of a subgroup of patients who were treated with 5-aminosalicylate as maintenance monotherapy during the first year of disease. METHODS: In a European community-based inception cohort, 488 patients with Crohn's disease were followed from the time of their diagnosis. Information on clinical data, demographics, disease activity, medical therapy and rates of surgery, cancers and deaths was collected prospectively. Patient management was left to the discretion of the treating gastroenterologists. RESULTS: Overall, 292 (60%) patients with Crohn's disease received 5-aminosalicylate period during follow-up for a median duration of 28 months (interquartile range 6-60). Of these, 78 (16%) patients received 5-aminosalicylate monotherapy during the first year following diagnosis. Patients who received monotherapy with 5-aminosalicylate experienced a mild disease course with only nine (12%) who required hospitalization, surgery, or developed stricturing or penetrating disease, and most never needed more intensive therapy. The remaining 214 patients were treated with 5-aminosalicylate as the first maintenance drug although most eventually needed to step up to other treatments including immunomodulators (75 (35%)), biological therapy (49 (23%)) or surgery (38 (18%)). CONCLUSION: In this European community-based inception cohort of unselected Crohn's disease patients, 5-aminosalicylate was commonly used. A substantial group of these patients experienced a quiescent disease course without need of additional treatment during follow-up. Therefore, despite the controversy regarding the efficacy of 5-aminosalicylate in Crohn's disease, its use seems to result in a satisfying disease course for both patients and physicians.

Health-care costs of inflammatory bowel disease in a pan-European, community-based, inception cohort during 5 years of follow-up: a population-based study.

BACKGROUND: Inflammatory bowel disease (IBD) places a significant burden on health-care systems because of its chronicity and need for expensive therapies and surgery. With increasing use of biological therapies, contemporary data on IBD health-care costs are important for those responsible for allocating resources in Europe. To our knowledge, no prospective long-term analysis of the health-care costs of patients with IBD in the era of biologicals has been done in Europe. We aimed to investigate cost profiles of a pan-European, community-based inception cohort during 5 years of follow-up. METHODS: The Epi-IBD cohort is a community-based, prospective inception cohort of unselected patients with IBD diagnosed in 2010 at centres in 20 European countries plus Israel. Incident patients who were diagnosed with IBD according to the Copenhagen Diagnostic Criteria between Jan 1, and Dec 31, 2010, and were aged 15 years or older the time of diagnosis were prospectively included. Data on clinical characteristics and direct costs (investigations and outpatient visits, blood tests, treatments, hospitalisations, and surgeries) were collected prospectively using electronic case-report forms. Patient-level costs incorporated procedures leading to the initial diagnosis of IBD and costs of IBD management during the 5-year follow-up period. Costs incurred by comorbidities and unrelated to IBD were excluded. We grouped direct costs into the following five categories: investigations (including outpatient visits and blood tests), conventional medical treatment, biological therapy, hospitalisation, and surgery. FINDINGS: The study population consisted of 1289 patients with IBD, with 1073 (83%) patients from western Europe and 216 (17%) from eastern Europe. 488 (38%) patients had Crohn's disease, 717 (56%) had ulcerative colitis, and 84 (6%) had IBD unclassified. The mean cost per patient-year during follow-up for patients with IBD was €2609 (SD 7389; median €446 [IQR 164-1849]). The mean cost per patient-year during follow-up was €3542 (8058; median €717 [214-3512]) for patients with Crohn's disease, €2088 (7058; median €408 [133-1161]) for patients with ulcerative colitis, and €1609 (5010; median €415 [92-1228]) for patients with IBD unclassified (p<0·0001). Costs were highest in the first year and then decreased significantly during follow-up. Hospitalisations and diagnostic procedures accounted for more than 50% of costs during the first year. However, in subsequent years there was a steady increase in expenditure on biologicals, which accounted for 73% of costs in Crohn's disease and 48% in ulcerative colitis, in year 5. The mean annual cost per patient-year for biologicals was €866 (SD 3056). The mean yearly costs of biological therapy were higher in patients with Crohn's disease (€1782 [SD 4370]) than in patients with ulcerative colitis (€286 [1427]) or IBD unclassified (€521 [2807]; p<0·0001). INTERPRETATION: Overall direct expenditure on health care decreased over a 5-year follow-up period. This period was characterised by increasing expenditure on biologicals and decreasing expenditure on conventional medical treatments, hospitalisations, and surgeries. In light of the expenditures associated with biological therapy, cost-effective treatment strategies are needed to reduce the economic burden of inflammatory bowel disease. FUNDING: Kirsten og Freddy Johansens Fond and Nordsjællands Hospital Forskningsråd.

Outcome of acute severe ulcerative colitis in patients previously exposed to immunosuppressive therapy.

BACKGROUND AND AIM: We aimed to evaluate the outcome of patients with acute severe ulcerative colitis previously exposed to immunosuppressive (IMS) therapy. METHODS: We retrospectively collected data from 86 consecutive patients from 2008. Early outcome was evaluated as response to steroids, rescue therapy, and colectomy rate, whereas colectomy free-survival was determined along the follow-up. RESULTS: The overall response rates to steroids and rescue therapy was 33.7% and 90.5%, respectively, while early colectomy rate was 22.1%. Patients previously treated with IMS (n=47) showed a trend towards lower response to steroids (25.5% vs 43.6%; p=0.10), and a high-risk of early colectomy (29.8% vs 12.8%; p=0.07), but a similar response to rescue therapy (87.5% vs 94.4%, p=0.62) when compared with IMS-naïve patients (n=39). The overall cumulative probability to avoid the surgery was 67.5% and 56.6% at 12 and 60 months, respectively, regardless of previous exposure to IMS (p=0.30). At multivariate analysis the risk of early colectomy was increased by previous IMS (OR 5.16, p=0.017), anaemia (OR 4.26, p=0.02), and diagnosis above 40 years (OR 5.31, p=0.011). CONCLUSIONS: Patients previously treated with IMS showed a non-significant trend towards a worse response with steroid therapy, a satisfactory response rate to rescue therapy, and a similar probability of avoiding colectomy during the follow-up vs IMS-naive patients.

Disease Course and Colectomy Rate of Ulcerative Colitis: A Follow-up Cohort Study of a Referral Center in Tuscany.

BACKGROUND: The disease course and colectomy rate of ulcerative colitis (UC) vary largely in population-based and referral center cohorts. We retrospectively evaluated our cohort to determine the disease course and risk factors for colectomy. METHODS: A cohort of 1723 ulcerative colitis patients (986 males; mean age, 34.8 ± 15.4 yrs) were identified and followed since 1960s for a mean of 11 ± 9 years (range, 1-49 yrs). RESULTS: The disease extension was classified as E1, E2, and E3 on diagnosis at 19.7%, 54.2%, and 26.1% of patients, respectively. At the final follow-up, the disease extension increased in 20% of the cases. Extraintestinal manifestations (EIMs) were reported by 11% of the patients, whereas systemic corticosteroids (CS), IM or anti-TNFα agents were used by 68.6%, 20.4%, and 6.4% of patients, respectively. The crude colectomy rate was 7% (120 pts), with a 1.2% rate (n = 21) at 1 year from diagnosis (95% CI, 0.7-1.7) and a Kaplan-Meyer estimation of up to 18.2% after 30 years of follow-up. The 1-year colectomy rate showed no significant difference through the decades, whereas the 5-year and 10-year absolute value of colectomy was halved in the last 2 decades compared with the period from 1960 to 1990 (P = 0.01), with a general trend of a reduced colectomy rate at survival curves (P = 0.056). CONCLUSIONS: The colectomy rate was low in our cohort and further reduced in the last 2 decades. However, despite the availability of anti-TNFα agents, no further significant reduction of colectomies was observed in the last decade.

Thrombosis in inflammatory bowel diseases: what's the link?

Inflammatory bowel disease affects more than 2 million people in Europe, with almost 20% of patients being diagnosed in pediatric age. Patients with inflammatory bowel disease are at increased risk of thromboembolic complications which may affect patients' morbidity and mortality. The risk of the most common thromboembolic events, such as deep venous thrombosis and pulmonary embolism, are estimated to be three-fold increased compared to controls, but many other districts can be affected. Moreover, patients with ulcerative colitis and Crohn's disease experience thromboembolic events at a younger age compared to general population. Many factors have been investigated as determinants of the pro-thrombotic tendency such as acquired risk factors or genetic and immune abnormalities, but a unique cause has not been found. Many efforts have been focused on the study of abnormalities in the coagulation cascade, its natural inhibitors and the fibrinolytic system components and both quantitative and qualitative alterations have been demonstrated. Recently the role of platelets and microvascular endothelium has been reviewed, as the possible link between the inflammatory and hemostatic process.

Adalimumab-induced lupus erythematosus with central nervous system involvement in a patient with Crohn's disease.

The anti-tumor necrosis factor (TNF) agents are drugs that in recent years turned out to be a mainstay of therapy for the treatment of inflammatory bowel disease. Nevertheless, they have several adverse effects such as infectious complications and immunogenicity. One of the most common immunogenic effects is the development of autoantibodies, mainly anti-nuclear antibodies and anti-double-stranded DNA antibodies, only rarely associated with overt clinical manifestations of systemic lupus erythematosus. Adalimumab is a fully humanized monoclonal antibody widely used for the treatment of Crohn's disease and supposed to have less immunogenic activity and a safer profile than other anti-TNF agents. The occurrence of systemic lupus erythematosus with involvement of the central nervous system appears to be a very rare complication of such drugs, and no cases have been reported in the medical literature in patients treated with adalimumab. We report a case of a 53 years-old woman with ileo-colic Crohn's disease where the treatment with adalimumab was complicated by systemic lupus erythematosus with central nervous system vasculitis.