Switching maintenance infliximab therapy to biosimilar infliximab in inflammatory bowel disease patients

Background: Clinical use of biosimilar infliximab (CT-P13) in inflammatory bowel diseases (IBDs) is based on extrapolation of indication from clinical studies performed in rheumatological diseases. Only few data exist of behaviour of infliximab trough levels (TLs) and anti-drug antibodies (ADAs) during switching.

Aim: The objective of this study was to evaluate changes in TLs, ADA formation and disease activity after switching from originator infliximab to biosimilar one.

Methods: All our IBD patients receiving maintenance infliximab therapy were switched to biosimilar infliximab. TLs and ADAs were measured before the last originator infusion and before the third biosimilar infusion. Laboratory values, disease activity indices (partial Mayo score and Harvey–Bradshaw index) and demographic data were collected from patient records.

Results: A total of 62 patients were included in the final analysis (32 Crohn’s disease, 30 ulcerative colitis (UC) or IBD-unclassified). No significant changes in median TLs before (5.5?mg/l) and after switching (5.5?mg/l, p?=?.05) occurred in the entire study group or in the Crohn’s disease (CD) subgroup (5.75 and 6.5?mg/l, p?=?.68). However, in the subgroup of ulcerative colitis, the change in median TL was significantly different (from 5.2 to 4.25?mg/l, p?=?.019). Two patients developed ADAs after switching. No changes in disease activity were detected during switching and no safety concerns occurred.

Conclusions: Switching from originator to biosimilar infliximab resulted in statistically significant differences in infliximab TLs in patients with UC but not in patients with Crohn’s disease. The clinical significance for this difference is doubtful and in neither group changes in disease activity occurred.     

Higher vedolizumab serum levels do not increase the risk of adverse events in patients with inflammatory bowel disease

Abstract

Background: Although its mechanism of action may confer a safety benefit, vedolizumab has still been associated with adverse events (AE). We investigated whether inflammatory bowel disease (IBD) patients with higher trough vedolizumab serum levels experienced an increased risk of AEs.

Methods: This was a retrospective study of 76 IBD patients with at least one measurement of serum vedolizumab available. Vedolizumab levels ranged from <3.5?mcg/mL to 87.2?mcg/mL (median = 15.8?mcg/mL). The primary outcome was the rate of overall AEs. Secondary outcomes included the rates of infections, dermatologic reactions, infusion reactions, and other AEs. Multivariate logistic regression analysis was performed to evaluate the relationship between serum vedolizumab levels and AEs.

Results: 19 patients out of 76 reported AEs. In patients with higher vedolizumab levels, there were 10 AEs reported out of 38 patients, which was not significantly different from the 9 AEs reported in 38 patients with lower vedolizumab levels (26.3% vs. 23.7%, p?=?.79). After adjustment for potential covariates, IBD patients with higher vedolizumab levels did not have higher odds of an AE than patients with lower levels (OR 0.92, 95% CI 0.30–2.81). Longer duration of therapy had higher odds of AEs, (OR of 1.04 at 95% CI 1.00–1.09, p?=?.0494 per additional month). None of the other variables were associated with a greater risk of AEs.

Conclusions: There does not appear to be an increased risk of adverse events in IBD patients with higher vedolizumab levels, but duration of therapy may increase the risk of AEs.     

Development of psoriasis in IBD patients under TNF-antagonist therapy is associated neither with anti-TNF-antagonist antibodies nor trough levels

Background: The cause of anti-TNF-induced psoriasis is still unknown.

Objective: We aimed to evaluate if the appearance of psoriasis under anti-TNF therapy is associated with anti-TNF antibody levels and TNF-antagonist trough levels.

Methods: In this case-control study we identified 23 patients (21 with Crohn’s disease [CD], two with ulcerative colitis [UC]) who developed psoriasis under infliximab (IFX, n?=?20), adalimumab (ADA, n?=?2), and certolizumab pegol (CZP, n=?1) and compared them regarding the anti-TNF-antagonist antibody levels with 85 IBD patients (72 with CD, 13 with UC) on anti-TNF therapy without psoriasis.

Results: Median disease duration was not different between the two groups (7 years in the group with psoriasis under TNF-antagonists vs. 10 years in the control group, p?=?0.072). No patient from the psoriasis group had antibodies against TNF-antagonists compared to 10.6% in the control group (p?=?0.103). No difference was found in IFX trough levels in the group of patients with psoriasis compared to the control group (2.6?μg/mL [IQR 0.9–5.5] vs. 3.4?μg/mL [IQR 1.4–8.1], p?=?0.573). TNF-antagonist therapy could be continued in 91.3% of patients with TNF-antagonist related psoriasis and most patients responded to topical therapies.

Conclusion: Anti-TNF-induced psoriasis seems to be independent of anti-TNF antibodies and trough levels. Interruption of Anti-TNF therapy is rarely necessary.     

Factors Associated with the Immunogenicity of Anti-Tumor Necrosis Factor Agents in Pediatric Patients with Inflammatory Bowel Disease

Background/AimsAnti-drug antibodies (ADAs) can develop during treatment with anti-tumor necrosis factor (TNF) agents. We aimed to investigate the factors associated with immunogenicity of anti-TNF agents in pediatric patients with inflammatory bowel disease (IBD) and observe the clinical course of ADA-positive patients.MethodsPediatric IBD patients receiving maintenance treatment with anti-TNF agents who had been tested for ADAs against infliximab (IFX) or adalimumab (ADL) were included in this cross-sectional study. Factors associated with ADA positivity were investigated by analyzing clinicodemographic, laboratory, and treatment-related factors.ResultsA total of 76 patients (Crohn’s disease, 65; ulcerative colitis, 11) were included. Among these, 59 and 17 patients were receiving IFX and ADL, respectively. ADAs were found in 10 patients (13.2%), all of whom were receiving IFX. According to multivariable logistic regression analysis, the IFX trough level (TL) was associated with ADA positivity (odds ratio, 0.25; 95% confidence interval [CI], 0.08 to 0.51; p=0.002). According to the receiver operating characteristic analysis, the optimal cutoff of the IFX TLs for stratifying patients based on the presence of ADAs against IFX was 1.88 μg/mL (area under curve, 0.941; 95% CI, 0.873 to 1.000; sensitivity, 80.0%; specificity, 95.9%; p<0.001). Among the 10 patients with ADAs against IFX, five patients (50%) switched to ADL within 1 year, while five patients (50%) kept receiving IFX. Transient ADAs were observed in three patients (30%).ConclusionsIFX TL was the only factor associated with ADA formation in pediatric IBD patients receiving IFX. Future studies based on serial and proactive therapeutic drug monitoring are required in the future.     

Tolerability profile of thiopurines in inflammatory bowel disease: a prospective experience

Objectives: The occurrence of thiopurine-related adverse events (AEs) may complicate the management of patients with inflammatory bowel disease (IBD). We aimed to evaluate the tolerability of thiopurines in a current IBD setting.

Materials and methods: All consecutive patients who started a treatment with azathioprine (AZA) from January 2010 to March 2016 were entered in a prospectively maintained database, and the AEs which led to the permanent discontinuation of the drug were reported.

Results: Two hundred and fifty three patients were included. Median total follow-up was 32 months (range: 0.2–75 months). At the end of the study, AZA was discontinued in 160 patients (63.2%). The main reason leading to drug withdrawal was the occurrence of AEs (109/160 patients [68.1%]; cumulative incidence among the entire cohort: 43.1%). Overall, the most frequent AEs leading to treatment withdrawal were nausea (31/253 patients, 12.3%) and subjective symptoms, i.e., poorly defined side effects such as fatigue, headache and muscle pain (20/253 patients, 7.9%). Among the 109 AZA-intolerant patients, a switch to 6-mercaptopurine (6-MP) was performed in 44 cases (40.4%). At the end of follow-up, 6-MP was discontinued in 35/44 patients (79.5%), mostly due to AEs (29/35 patients, 82.8%). Azathioprine-induced hepatic and pancreatic toxicity was associated with male gender (p?=?.01 and p?=?.03, respectively), and occurrence of nausea with Crohn’s disease (p?=?.04).

Conclusions: Our real-life prospective cohort showed the higher cumulative incidence of thiopurine withdrawal due to AEs reported to date. Switching from AZA to 6-MP was often ineffective.     

Concurrent immunomodulator therapy is associated with higher adalimumab trough levels during scheduled maintenance therapy

Introduction: Combination therapy with infliximab and immunomodulators is superior to monotherapy, resulting in better outcomes and higher trough levels of infliximab. The role of concurrent immunomodulatory therapy on adalimumab trough levels has not been adequately investigated. We evaluated the impact of concomitant immunomodulation on adalimumab trough levels in patients on scheduled maintenance therapy.

Method: We conducted a prospective observational, cross-sectional study of all inflammatory bowel disease patients on maintenance therapy who had adalimumab trough levels measured between January 2013 and January 2016. Drug level and anti-drug antibody measurements were performed on sera using a solid phase assay. Pairwise comparison of means was used to compare trough levels in patients with and without concomitant immune modulator therapy.

Results: In total, 79 patients were included. Twenty-three patients (29.1%) were on weekly dosing whereas 56 (70.9%) were on alternate weeks. Median adalimumab trough levels were comparable in patients with and without clinical remission (6.8?μg/ml (IQR 5.6–8.1) versus 6.7?μg/ml (IQR 3.9–8.1), respectively. Patients with an elevated faecal calprotectin?>250?μg/g had lower adalimumab trough levels (median 6.7, IQR 3.9–8) compared to patients with faecal calprotectin?<250?μg/g (median 7.7, IQR 6.1–8.1) though this did not achieve statistical significance (p?=?.062). Median adalimumab trough levels among patients on concurrent immunomodulators was 7.2?μg/ml (IQR 5.7–8.1) compared to those not on concurrent immunomodulator, 6.1?μg/ml (IQR 2.7–7.7, p?=?.0297).

Conclusion: Adalimumab trough levels were significantly higher in patients on concurrent immunomodulators during maintenance therapy. There was a trend towards a lower adalimumab trough level in patients with elevated calprotectin.     

Relapse rates and predictors for relapse in a real-life cohort of IBD patients after discontinuation of anti-TNF therapy

Objective: We investigated relapse rates after anti-tumor necrosis factor (anti-TNF) withdrawal in inflammatory bowel disease (IBD) patients, response to restart of anti-TNF treatment and predictors for relapse.

Methods: IBD patients in remission receiving infliximab or adalimumab treatment for ≥1 year who discontinued treatment were included. Relapse rates and predictors for relapse were studied using survival and Cox regression analysis.

Results: In total, 101 patients were included (77?CD, 24 UC). A total of 56 patients (55%) experienced a relapse (CD 38, UC 18) with a median time to relapse of 32 and 18 months in CD and UC, respectively. Of patients that were retreated with the same anti-TNF agent, 84% responded. A trough serum concentration ≥2 µg/ml within 1 year prior to anti-TNF discontinuation was associated with a higher relapse rate in CD patients (HR 2.89; p?=?.018), which was more evident in patients requiring retreatment with biologicals, bowel-related surgery or experimental medication (HR: 4.18; p?=?.009). A young age (<17 years) at diagnosis was associated with a higher relapse rate (HR: 2.29; p?=?.040) and fecal calprotectin levels <25?µg/g with a lower relapse rate in CD patients (HR: 0.34; p?=?.041). Relapse rates, requiring treatment with biologicals or experimental medication, was lower in UC patients who continued immunosuppressive treatment (HR: 0.26; p?=?.042).

Conclusions: Approximately 55% of patients relapsed after anti-TNF withdrawal with a median time to relapse of 32 and 18 months in CD and UC, respectively. Retreatment with the same anti-TNF was successful in 84% of patients.     

Adalimumab trough serum levels and anti-adalimumab antibodies in the long-term clinical outcome of patients with Crohn’s disease

Objective: Few data are available on the relevance of adalimumab (ADA) trough serum levels and anti-ADA antibodies (AAA) during long-term follow-up of patients with Crohn’s Disease (CD), and their association with disease outcome. In this study, our aim was to assess ADA trough serum levels and the presence of AAA according to disease activity and clinical response during long-term follow-up in a series of patients with CD treated with ADA monotherapy.

Material and methods: We prospectively evaluated 23 consecutive, infliximab-naïve CD patients who achieved clinical remission/response after induction and were in maintenance treatment with ADA, and who were followed-up for at least 72 weeks. Blood samples were drawn at standardized time points to assess ADA through levels, AAA.

Results: At week 48, we found significantly (p?=?0.027) different ADA trough serum levels in patients in remission (10.1?mcg/mL), mild (7.4?mcg/mL), and moderate/severe disease (4.5?mcg/mL). Median ADA trough levels were significantly lower in patients with AAA (3.7?mcg/mL versus 9.3?mcg/mL, p?=?0.006). At the end of follow-up (median 102 weeks, range 73–112 weeks), ADA trough serum concentrations were significantly higher (11.9?mcg/mL) as compared to patients with mild and moderate/severe disease (5.5?mcg/mL, p?=?0.0002). Furthermore, median ADA trough concentrations showed a trend towards lower levels in AAA positive patients (5.2?mcg/mL versus 7.2?mcg/mL, p?=?0.371).

Conclusions: Our results emphasize the relevance of therapeutic drug monitoring in CD patients on biologic treatment. ADA trough serum levels and the presence of AAA are important features in the management of patients on ADA treatment.     

Circadian rhythm abnormalities in patients with inflammatory bowel disease – association with adipokine profile

Abstract

Background: The role of sleep disturbances in patients with inflammatory bowel disease (IBD) remained relatively unknown. The aim of this study was to identify the adipokine profile in the patients with IBD and its relationship with the circadian rhythm disorders.

Methods: Prospective, observational cohort study was performed. In all the enrolled adult IBD patients, the disease activity was assessed by using Crohn’s Disease Activity Index (CDAI) for Crohn’s disease (CD) and Partial Mayo Score for ulcerative colitis (UC), respectively. All patients were also asked to respond to a questionnaire to define Pittsburgh Quality Sleep Index (PSQI). From all the enrolled patients, 15?mL venous blood was taken to determine adipokine levels and perform standard laboratory tests.

Results: Sixty-five IBD patients were enrolled in our study: 30 with CD and 35 with UC. Poor sleep was noted in 69.2% patients with clinically active and in 7.7% patients with inactive disease (p?=?.0023). In the group of IBD patients with poor sleep, the significantly higher level of serum resistin (p?=?.0458), and lower level of serum adiponectin and leptin (p?=?.0215, p?=?.0201; respectively) were observed. In the IBD patients with exacerbation, the significantly higher level of serum resistin (p?=?.0396), significantly lower serum level of leptin (p?=?.0453) and tendency to lower serum level of adiponectin (p?=?.1214) were recorded.

Conclusions: The relationship between circadian rhythm abnormalities and specific adipokine profile may show us a risk factor of developing inflammatory intestinal lesions in IBD patients. This knowledge may allow the treatment of sleep disturbances, body weight-control and dietary habits become new targets in IBD therapy.     

Crohn's disease outpatients treated with adalimumab have an earlier secondary loss of response and requirement for dose escalation compared to infliximab: A real life cohort study

BackgroundThe efficacy of anti-tumor necrosis factor alpha agents in maintaining remission in Crohn's disease may wane over time, leading to secondary loss of response that can often be overcome with dose escalation. Comparison of secondary loss of response of adalimumab and infliximab during long-term treatment of CD in a real-life IBD clinic has not been previously evaluated.MethodsA retrospective cohort study was conducted evaluating outpatients with CD on a maintenance regimen with adalimumab or infliximab from 200 to 2013 and who experienced a secondary loss of response. All infliximab-treated patients were anti-TNF naïve. Adalimumab-treated patients were stratified by prior anti-TNF exposure. Kaplan–Meier analysis was conducted to compare time to loss of response.Results218 CD patients met inclusion criteria (117 infliximab, 101 adalimumab). Median follow-up duration was 170.0 weeks for infliximab and 122.0 weeks for adalimumab (p = 0.61). The proportion of patients with secondary loss of response was similar for infliximab-treated — 51.3% (60/117) compared to adalimumab patients naïve to anti-TNF therapy — 60.5% (23/38) (p = 0.32), and adalimumab patients with prior anti-TNF exposure — 65.1% (41/63) (p = 0.08). Median time to secondary loss of response was longer for infliximab patients (99.3 wk, IQR 55.7–168.5) compared to both adalimumab patients naïve to anti-TNF therapy (58.9 wk, IQR 29.0–85.7) (p = 0.03), and adalimumab patients with prior anti-TNF exposure (52.7 wk, IQR 20.1–85.0) (p < 0.001).ConclusionsOver 50% of CD patients treated with infliximab and adalimumab develop secondary loss of response. Time to loss of response was shorter in patients treated with adalimumab compared to those treated with infliximab. Prior anti-TNF exposure further accelerated time to loss of response.     

The association of psoriasiform rash with anti-tumor necrosis factor (anti-TNF) therapy in inflammatory bowel disease: A single academic center case series

Background & AimsAnti-tumor necrosis factors (anti-TNF) including infliximab, adalimumab and certolizumab pegol are used to treat Crohn's disease (CD) and ulcerative colitis (UC). Paradoxically, while also indicated for the treatment of psoriasis, anti-TNF therapy has been associated with development of psoriasiform lesions in IBD patients and can compel discontinuation of therapy. We aim to investigate IBD patient, clinical characteristics, and frequency for the development of and outcomes associated with anti-TNF induced psoriasiform rash.MethodsWe identify IBD patients on anti-TNFs with an onset of a psoriasiform rash. Patient characteristics, duration of anti-TNF, concomitant immunosuppressants, lesion distribution, and outcomes of rash are described.ResultsOf 1004 IBD patients with exposure to anti-TNF therapy, 27 patients (2.7%) developed psoriasiform lesions. Psoriasiform rash cases stratified by biologic use were 1.3% for infliximab, 4.1% for adalimumab, and 6.4% for certolizumab. Average time on treatment (206.3 weeks) and time on treatment until onset of psoriasiform lesions (126.9 weeks) was significantly higher in the infliximab group. The adalimumab group had the highest need for treatment discontinuation (60%). The majority (59.3%) of patients were able to maintain on anti-TNFs despite rash onset. Among patients that required discontinuation (40.7%), the majority experienced improvement with a subsequent anti-TNF (66.7%).Conclusion27 cases of anti-TNF associated psoriasiform lesions are reported. Discontinuation of anti-TNF treatment is unnecessary in the majority. Dermatologic improvement was achieved in the majority with a subsequent anti-TNF, suggesting anti-TNF induced psoriasiform rash is not necessarily a class effect.     

Evolution of cytokines and inflammatory biomarkers during infliximab induction therapy and the impact of inflammatory burden on primary response in patients with Crohn’s disease

Objective: Primary non-response to infliximab in Crohn’s disease is still incompletely understood. Our aim was to further characterize the role of inflammatory burden during infliximab induction therapy.

Materials and Methods: We studied a well-characterized cohort of 201 anti-TNF naive Crohn’s disease patients treated with infliximab 5mg/kg at week 0, 2, 6 and 14 who had serum samples drawn just before every infusion. All serum samples were analyzed for CRP, albumin, TNF, IFN-γ, IL-6, IL-8, IL-10, infliximab trough concentrations (in-house-developed ELISA) and antibodies to infliximab (HMSA, Prometheus Laboratories Inc., San Diego, CA). Primary non-response was defined as the absence of clinical improvement at week 14.

Results: The incidence of primary non-response to infliximab was 8% (n?=?16). IL-8 concentrations at baseline were higher (p?=?.01) and albumin at week 6 was lower in primary non-responders (p?=?.01) compared to responders. During induction, IFN-γ and IL-6 concentrations decreased significantly at week 2 and week 6 in responders compared to primary non-responders (p?<?.05). Serum TNF increased significantly after each infliximab infusion and this increase from week 0 to week 14 was more pronounced in responders (p?=?.03). Multiple logistic regression identified TNF/CRP ratio at baseline as predictive for primary non-response to infliximab at week 14 (OR 2.8 (95% CI 1.4–5.5; p?=?.003)).

Conclusions: In this intensively sampled cohort of Crohn’s disease patients, we demonstrate that inflammatory burden is more determining for primary non-response than drug exposure or immunogenicity. Our findings furthermore suggest that the contribution of TNF in inflammation might be higher in primary non-response, contradicting the non-TNF-driven concept.     

Costs of adalimumab versus infliximab as first-line biological therapy for luminal Crohn's disease

Background and aimsRandomised controlled trials demonstrate that the anti-tumour necrosis factor-α (anti-TNFα) therapies infliximab and adalimumab are effective in inducing remission and preventing relapse of Crohn's disease (CD). As few studies have compared costs and efficacy of these two drugs directly, we examined this issue.MethodsData were collected for patients receiving either drug as first-line anti-TNFα for CD. Patients were matched as closely as possible on age, gender, weight, height, and date of commencement of therapy. Response to induction therapy was assessed at 12 weeks, and sustained clinical benefit at last point of follow-up. Resource data were collected for all patients until study end, with National Health Services reference costs applied to calculate the total cost per patient with adalimumab compared with infliximab.ResultsThirty-six patients had been treated with adalimumab as first-line anti-TNFα since 2010. We matched an identical number of infliximab patients. Demographic data were similar between the two groups. Costs were significantly lower with adalimumab (£6692.95 less per patient (95% confidence interval £1816.61–£11569.29)), which was largely driven by the drug costs and drug administration costs associated with infliximab. Twenty-nine (80.6%) patients responded to induction therapy with both drugs, and 22 (61.1%) achieved glucocorticosteroid-free sustained clinical benefit with either drug at last point of follow-up.ConclusionsCosts of infliximab used as first-line anti-TNFα therapy are greater, which may have implications for selection. Clinical outcomes appeared comparable, although power to detect a statistically significant difference would be limited.     

Success and safety of high infliximab trough levels in inflammatory bowel disease

Objective: A prospective trial suggests target infliximab trough levels of 3–7?μg/mL, yet data on additional therapeutic benefits and safety of higher trough levels are scarce.

Aim: To explore whether high infliximab trough levels (≥7?μg/mL) are more effective and still safe.

Material and methods: In this cohort study of 183 patients (109 Crohn’s disease and 74 ulcerative colitis) on infliximab maintenance treatment at a tertiary referral center we correlated fecal calprotectin and C-reactive protein to trough levels (426 samples) at different time points during treatment. Rates of infections were compared in quadrimesters (four-month periods) with high trough levels to quadrimesters with trough levels <7?μg/mL during 420 patient-years.

Results: Fecal calprotectin and C-reactive protein (median [interquartile range]) were lower in patients with high trough levels (fecal calprotectin 66?mg/kg [30–257]; C-reactive protein 3?mg/L [3–3]) compared to trough levels below 7?μg/mL (fecal calprotectin 155?mg/kg [72–474]; C-reactive protein 3?mg/L [3–14.5]) (p?p?=?.32). Maintaining high trough levels resulted in 32% (interquartile range: 2–54%) increase of infliximab consumption.

Conclusion: High infliximab trough levels provide better control of inflammation in inflammatory bowel disease without increasing the risk of infection.     

Adalimumab versus azathioprine to halt the progression of bowel damage in Crohn’s disease: application of Lémann Index

Abstract

Background: The Lémann Index (LI) was recently developed to evaluate the cumulative bowel damage in patients with Crohn’s disease (CD).

Aims: To search for a difference between adalimumab and azathioprine to halt the progression of bowel damage in active CD, using the LI.

Methods: A single-centre, retrospective study was conducted. Patients with CD were included if they had colonoscopy and magnetic resonance enterography performed within 4?months from the start of adalimumab or azathioprine and repeated after 12?months of therapy. Primary outcome was reached if the increase of LI after 12?months of treatment was <0.3, the drug was not stopped, and the use of systemic steroids was continued for no more than 3?months.

Results: Ninety-one patients were enrolled, 31 (34.1%) of them treated with adalimumab and 60 (65.9%) with azathioprine. Sixty-seven percent of patients treated with adalimumab reached the primary outcome compared to 28.3% of patients treated with azathioprine (p?=?.0006). The LI in the group on adalimumab therapy decreased after 12?months (from 9.9 to 8.8), while in the group on azathioprine therapy it increased (from 7.7 to 8.8).

Conclusion: Treatment with adalimumab halts the progression of bowel damage in CD while that with azathioprine does not.     

Altered body composition profiles in young adults with childhood-onset inflammatory bowel disease

Abstract

Background: Patients with inflammatory bowel disease (IBD) often develop alterations in body composition in terms of their proportions of lean mass and fat mass, as well as reduced bone mineral density (BMD). However, there are limited data on the skeletal muscle index (SMI) and percentage fat (fat %) for young adults with childhood-onset IBD. Our aim was to investigate the body compositions of these patients, with the focus on SMI and fat %.

Methods: Body composition was estimated by dual x-ray absorptiometry for 94 young adults with childhood-onset IBD aged 18–27?years, 65 of whom had ulcerative colitis. The Z-scores for SMI, fat %, and BMD were calculated using the normative data from 1,289 individuals with corresponding age. Based on the SMI and fat % Z-scores, each patient was classified as having a body composition profile that was: (i) normal; (ii) obese (fat % Z-score >1); (iii) myopenic (SMI Z-score <??1); or (iv) myopenic-obese.

Results: A higher proportion of young adults with childhood-onset IBD had a body composition profile classified as myopenic (24%) or myopenic-obese (9%), as compared to the controls (myopenic [16%, p?=?.016]; myopenic-obese [2%, p?=?.002]). Patients with the myopenic or myopenic-obese profile had significantly lower total body BMD Z-scores (?1.3?±?0.7 and ?1.4?±?0.9, respectively) than patients with the normal profile (?0.2?±?1.1; p?<?.001 and p?=?.004, respectively). Diagnosis of IBD in childhood represented an additional risk for low BMD, regardless of SMI Z-score.

Conclusion: Young adults with childhood-onset IBD have a high risk for having altered body composition traits.

• Summary

• Young adults with childhood-onset IBD carry a high risk for altered body composition traits. The myopenic and myopenic-obese body composition profiles were more frequently observed in patients with IBD than controls, and these profiles were strongly associated with low BMD.

     

Anti-TNF dose escalation and drug sustainability in Crohn’s disease: Data from the nationwide administrative database in Hungary

BackgroundA significant percentage of patients receiving anti-tumor necrosis factor alpha (anti-TNFα) agents lose clinical response over time. This study aims to provide representative real-world data on anti-TNFα drug sustainability, prevalence and predictors of anti-TNFα dose escalation.MethodsIn this nationwide, retrospective study, patients receiving infliximab or adalimumab therapy between 2013 and 2016 were included using the administrative claims database of the Hungarian National Health Insurance Fund. Demographic characteristics, drug sustainability, dose escalation, use of parallel medications were analyzed.Results476 infliximab and 397 adalimumab patients were included. Dose escalation was observed in 7%, 9% and 22% of patients receiving originator/biosimilar infliximab and adalimumab during the complete follow-up, respectively. Dose escalation was associated with shorter disease duration (OR = 1.75, p = 0.026) and corticosteroid use. Drug retention rates were 62.7%, 72.3%, 75.4% after 1 year follow-up for Remicade®, Inflectra® and Humira®, which decreased to 38.3% and 52.1% for Remicade® and Humira® at 3 years. Drug sustainability was affected by steroid use prior biologic initiation in adalimumab treated patients (HR = 2.04, p < 0.001), while in infliximab treated patients dose escalation (HR = 0.51, p = 0.02) and gender (HR = 1.39, p = 0.033) were predictors of treatment discontinuation.ConclusionDose escalation rates were lower in this real-world administrative database study for both adalimumab and infliximab compared to published data. Drug retention rates were overall satisfactory, with no apparent difference between the legacy and biosimilar infliximab.     

CD99 refers to the activity of inflammatory bowel disease

Background: Inflammatory bowel disease (IBD), composed of Crohn’s disease (CD) and ulcerative colitis (UC), is an inflammatory autoimmune disease. CD99 has been reported to participate in migration of leukocytes and T cell activation. However, the roles of CD99 in IBD are obscure.

Materials and methods: CD99 expression was examined in peripheral blood mononuclear cells (PBMCs) and inflamed mucosa from IBD patients by qRT-PCR. Serum TNF-α and IL-17A levels were detected by ELISA. Correlations of CD99 expression with TNF-α, IL-17A, Crohn’s disease activity index (CDAI), simple endoscopic score for CD (SES-CD), Mayo index, and Truelove grading were performed by Pearson’s correlation.

Results: CD99 expression was increased in PBMCs and inflamed mucosa from active CD and UC patients, and CD99 expression was also increased in the inflamed mucosa compared with unaffected control from the same patients. Serum TNF-α and IL-17A levels were increased in active CD or UC patients, and positively correlated with CD99 expression in PBMCs (CD: r?=?.402, p?=?.009; r?=?.350, p?=?.025. UC: r?=?.289, p?=?.028; r?=?.322, p?=?.014). Moreover, CD99 expression in inflamed mucosa was correlated with CDAI, SES-CD, Mayo index, and Truelove grading (r?=?.410, p?=?.012; r?=?.341, p?=?.005; r?=?.366, p?=?.002; r?=?.312, p?=?.011).

Conclusion: CD99 expression is increased in patients with active IBD, and positively correlated with disease activity. Therefore, CD99 expression can be used as an index to evaluate the activity of IBD.     

Serum oncostatin M predicts mucosal healing in patients with inflammatory bowel diseases treated with anti-TNF,but not vedolizumab

BackgroundOncostatin M was recently highlighted as a promising biomarker for therapeutic effectiveness in inflammatory bowel diseases (IBD), with particular regard for infliximab. The primary aim was to evaluate the ability of serum oncostatin M to predict endoscopic response to different drugs in IBD.MethodsWe selected two different cohorts of patients with IBD, treated with anti-TNF (infliximab and adalimumab) or with vedolizumab. Therapeutic response was evaluated at week 54 in terms of mucosal healing. Serum oncostatin M and C-reactive protein were measured at baseline; fecal calprotectin was measured at baseline and after 14 weeks of treatment. We evaluated the association of these biomarkers with mucosal healing at week 54.ResultsAmong 66 patients treated with anti-TNFs and 68 treated with vedolizumab, 35 and 31 attained mucosal healing, respectively. Mucosal healing at 54 weeks was significantly associated with low oncostatin M levels at baseline in the anti-TNF cohort; the diagnostic accuracy of oncostatin M at baseline in predicting mucosal healing was 0.91 (95% CI 0.84 to 0.99) in the anti-TNF cohort and 0.56 (95% CI 0.43 to 0.70, P < 0.001) in the vedolizumab cohort. Mucosal healing was also associated with low fecal calprotectin levels at week 14 in both cohorts.ConclusionOur study suggests that serum oncostatin M is a drug-specific biomarker, since it could be used to predict therapeutic effectiveness to anti-TNFs but not to vedolizumab. Moreover, these results emphasize the utility of serum oncostatin M measurement in patients treated with anti-TNF.     

Long-term effectiveness of vedolizumab in inflammatory bowel disease: a national study based on the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG)

Objectives: Clinical trials have demonstrated the efficacy of vedolizumab in inflammatory bowel disease (IBD). However, these findings may not reflect the clinical practice. Therefore, we aimed to describe a vedolizumab-treated patient population and assess long-term effectiveness.

Materials and methods: Patients initiating vedolizumab between 1 June 2014 and 30 May 2015 were identified through the Swedish National Quality Registry for IBD. Prospectively collected data on treatment and disease activity were extracted. Clinical remission was defined as Patient Harvey Bradshaw index?<5 in Crohn’s disease (CD) and Patient Simple Clinical Colitis Activity index?<3 in ulcerative colitis (UC).

Results: Two-hundred forty-six patients (147?CD, 92 UC and 7 IBD-Unclassified) were included. On study entry, 86% had failed TNF-antagonist and 48% of the CD patients had undergone?≥1 surgical resection. After a median follow-up of 17 (IQR: 14–20) months, 142 (58%) patients remained on vedolizumab. In total, 54% of the CD- and 64% of the UC patients were in clinical remission at the end of follow-up, with the clinical activity decreasing (p?<?.0001 in both groups). Faecal-calprotectin decreased in CD (p?<?.0001) and in UC (p?=?.001), whereas CRP decreased in CD (p?=?.002) but not in UC (p?=?.11). Previous anti-TNF exposure (adjusted HR: 4.03; 95% CI: 0.96–16.75) and elevated CRP at baseline (adjusted HR: 2.22; 95% CI: 1.10–4.35) seemed to be associated with discontinuation because of lack of response. Female sex was associated with termination because of intolerance (adjusted HR: 2.75; 95% CI: 1.16–6.48).

Conclusion: Vedolizumab-treated patients represent a treatment-refractory group. A long-term effect can be achieved, even beyond 1 year of treatment.