Assessing adherence to infusion-based biologic therapies in patients with inflammatory bowel disease.

BACKGROUND: The intravenous biologics infliximab and vedolizumab are effective long-term therapies for inflammatory bowel disease (IBD). Though highly effective, suboptimal adherence may result in loss of response and adverse sequelae. The extent and outcomes of suboptimal adherence with intravenous biologics, including in IBD, requires further evaluation. OBJECTIVES: To ascertain adherence to infliximab and vedolizumab infusions, and determine factors associated with poorer adherence within an IBD cohort. METHODS: A retrospective single-centre cohort study of IBD patients, assessing adherence to infliximab and vedolizumab over 2 years (July 1, 2017 to June 30, 2019) was conducted. Medical and pharmacy dispensing records were used to determine date of infusion. Adherence was assessed using the continuous, multiple interval measure of medication gaps (CMG). Objectively measured disease remission was achieved if one or more of endoscopic remission, faecal calprotectin <100 µg/mL and/or CRP <5 mg/mL occurred within 3 months of end of follow-up. Bivariate analysis and multiple linear regression elucidated factors associated with poorer adherence. RESULTS: Of 193 IBD patients, 132 (68.4%) had Crohn's disease. One hundred and thirty six (70.5%) patients received infliximab and 57 (29.5%) received vedolizumab with a median 13 [IQR 11-14] doses administered per patient over 2 years. Adherence according to CMG was similar between infliximab and vedolizumab groups (median 1.5% vs 1.2%, p = 0.31). In multiple linear regression analysis male sex, shorter IBD duration and clinic non-attendances were each associated with poorer adherence (Beta 4.69, 3.90, 3.56 respectively, p < 0.05) and objective disease remission was inversely associated with poorer adherence (Beta -3.27, p < 0.05). CONCLUSION: There was a wide range of adherence to biologic infusions in this IBD cohort with poorer adherence associated with patient related factors. Conversely, objectively measured remission was strongly associated with adherence. This emphasises the need for targeted interventions to improve adherence and monitoring, and mitigate treatment delays.

Examining maintenance care following infliximab salvage therapy for acute severe ulcerative colitis.

BACKGROUND AND AIM: Data supporting the optimal maintenance drug therapy and strategy to monitor ongoing response following successful infliximab (IFX) induction, for acute severe ulcerative colitis (ASUC), are limited. We aimed to evaluate maintenance and monitoring strategies employed in patients post-IFX induction therapy. METHODS: Patients in six Australian tertiary centers treated with IFX for steroid-refractory ASUC between April 2014 and May 2015 were identified via hospital IBD and pharmacy databases. Patients were followed up for 1 year with clinical data over 12 months recorded. Analysis was limited to patient outcomes beyond 3 months. RESULTS: Forty one patients were identified. Five of the 41 (12%) patients underwent colectomy within 3 months, and one patient was lost to follow-up. Six of 35 (17%) of the remaining patients progressed to colectomy by 12 months. Maintenance therapy: Patients maintained on thiopurine monotherapy (14/35) versus IFX/thiopurine therapy (15/35) were followed up. Two of 15 (13%) patients who received combination maintenance therapy underwent a colectomy at 12 months, compared with 1/14 (7%) patients receiving thiopurine monotherapy (P = 0.610). Monitoring during maintenance: Post-discharge, thiopurine metabolites were monitored in 15/27 (56%); fecal calprotectin in 11/32 (34%); and serum IFX levels in 4/20 (20%). Twenty of 32 (63%) patients had an endoscopic evaluation after IFX salvage with median time to first endoscopy of 109 days (interquartile range 113-230). CONCLUSION: Following IFX induction therapy for ASUC, the uptake of maintenance therapy in this cohort and strategies to monitor ongoing response were variable. These data suggest that the optimal maintenance and monitoring strategy post-IFX salvage therapy remains to be defined.

Factors associated with physical and cognitive fatigue in patients with Crohn's disease: a cross-sectional and longitudinal study.

BACKGROUND: Fatigue commonly impairs quality of life in patients with Crohn's disease (CD). This study aimed to evaluate the prevalence and severity of fatigue in CD (compared with ulcerative colitis [UC] and healthy controls) and to identify potentially modifiable factors associated with global, physical, and cognitive dimensions of fatigue. METHODS: Clinic attendees with confirmed CD or UC and healthy volunteers were surveyed on fatigue (Fatigue Impact Scale, FIS), psychological comorbidity, sleep quality, medication, and other clinical information. A CD subgroup also completed a similar follow-up survey. RESULTS: In 379 responders (181 CD, 113 UC, and 85 controls), global, physical, and cognitive FIS scores were highest in CD followed by UC and controls (P < 0.01), with a prevalence of global fatigue (total FIS ≥ 40) in 57% of CD patients. On multivariate analysis, concurrently active disease, poor sleep quality, and mental illness were significantly associated with all the 3 fatigue dimensions: regular vitamin B group supplementation was inversely associated with physical fatigue in the CD cohort and those of older age or with previous resection(s) (P = 0.05) were independently associated with cognitive fatigue only. Longitudinally in CD, fatigue scores remained constant between original and follow-up surveys (mean change in total FIS score +0.9; 95% confidence interval, -4.6 to 6.3). Factors independently associated with improved physical fatigue between surveys included avoidance of corticosteroids and establishment of regular exercise and with improved cognitive fatigue included cessation of immunomodulator therapy. CONCLUSIONS: Fatigue is highly prevalent and more severe in CD. Anticipated and novel associations with improvement of physical and/or cognitive fatigue were identified, offering clues to potential therapeutic approaches to ameliorating fatigue for clinical evaluation.