Dose-escalation of adalimumab, golimumab or ustekinumab in inflammatory bowel diseases: characterization and implications in real-life clinical practice.

OBJECTIVES: Dose-escalation is a common practice to optimize treatment with subcutaneously administered biologicals in Crohn's disease (CD) and ulcerative colitis (UC). However, limited data is available on the extent of dose-escalation in real-life. Here, we analyzed treatment persistence, dose-escalation, concomitant corticosteroid use, and costs of adalimumab, golimumab, and ustekinumab in inflammatory bowel diseases (IBD). METHODS: This was a nationwide, retrospective, non-interventional registry study. All adult patients who were diagnosed with CD or UC and had purchased adalimumab, golimumab, or ustekinumab from Finnish pharmacies between 2008 and 2018 were included in the study and followed up for 24 months after treatment initiation. RESULTS: A total of 2884 patients were included in the analyses. For adalimumab, treatment persistence was higher for CD patients compared to UC patients both at months 12 (46.2% versus 37.1%; p < .0001) and 24 (26.1% versus 19.7%; p < 0.0001). For golimumab (UC), treatment persistence was 48.3% at month 12 and 28.1% at month 24. The 12-month treatment persistence rate for patients on ustekinumab (CD) was 47.1%. Cumulative doses exceeding the regular dosing according to the summary of product characteristics (SPC), was observed for adalimumab in CD during the first 6 months of treatment (62.9% of the treatment periods), golimumab in the later stages of the UC treatment (52-54% of treatment periods at months 7-24), and ustekinumab during the first 6 months (70.7%). CONCLUSIONS: Based on this study, dose-escalation of subcutaneously administered biologicals is a common clinical practice in IBD. This has implications for treatment costs, use of concomitant medications, and treatment outcomes.

Characterization of inflammatory bowel disease management by vedolizumab and concomitant treatments in real-life clinical practice.

Limited data is available on vedolizumab combination therapies in real-world clinical practice. Here, we evaluated the concomitant corticosteroid, immunosuppressive, and 5-aminosalicylic acid utilization of inflammatory bowel disease (IBD) patients treated with vedolizumab in a nationwide, retrospective, non-interventional, multi-centre chart review study. All adult patients from 27 Finnish gastroenterology centres with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) who had at least one vedolizumab infusion since it's availability in Finland were included in the study. Data were collected from medical charts at baseline (vedolizumab treatment initiation), week 14, and month 6. The majority of patients who used corticosteroids at the baseline and persisted on vedolizumab treatment for 6 months were taken off corticosteroid treatment by the 6-month time point (CD, 54.5%; UC, 69.8%). Modest corticosteroid dose reductions were observed among treatment persistent CD patients from the baseline until month 6. Corticosteroid users had less vedolizumab discontinuations due to primary ineffectiveness and more discontinuations due to adverse events than patients not using corticosteroids. Vedolizumab may have a corticosteroid sparing effect in real-world clinical practice. Concomitant corticosteroid use may lead to a lower rate of vedolizumab discontinuation due to primary ineffectiveness, but a higher discontinuation rate due to adverse events.

High treatment persistence rate and significant endoscopic healing among real-life patients treated with vedolizumab - a Finnish Nationwide Inflammatory Bowel Disease Cohort Study (FINVEDO).

OBJECTIVES: The efficacy and tolerability of vedolizumab in the treatment of inflammatory bowel diseases (IBD) has been demonstrated in an extensive GEMINI clinical trial programme. Clinical trials represent highly selected patient populations and, therefore, it is important to demonstrate effectiveness in real-life clinical practice. We set out to assess real-world treatment outcomes of vedolizumab in a nationwide cohort of treatment refractory Finnish Crohn's disease (CD) and ulcerative colitis (UC) patients. METHODS: This was a nationwide, retrospective, non-interventional, multi-centre chart review study. All adult patients from 27 Finnish gastroenterology centers with a diagnosis of UC or CD who had at least one vedolizumab infusion since the availability of the product in Finland, were included in the study. Data were collected retrospectively from medical charts at baseline, week 14, and month 6. The primary outcome measure was treatment persistence 24 weeks post-vedolizumab initiation. RESULTS: A total of 247 patients were included (108 CD, 139 UC). A total of 75.0% (n = 81) of all CD patients and 66.2% (n = 92) of all UC patients, were persistent on vedolizumab therapy for 6 months post treatment initiation. At month 6, 41.8% (28/67) of the treatment persistent CD patients and 73.3% (63/86) of the treatment persistent UC patients achieved clinical remission. Significant improvement in endoscopic scores were observed among treatment persistent patients (CD, n = 17, ΔSES-CD=-5.5, p = .008; UC, n = 26, ΔMayo endoscopic score =-0.5, p = .003) at month 6. CONCLUSIONS: Vedolizumab provides an effective and well-tolerated treatment option in real-world clinical practice even among treatment refractory IBD patients.

Thirteen-year follow-up of early intervention with an inhaled corticosteroid in patients with asthma.

BACKGROUND: In a 3-year study, adult patients who recently developed asthma (symptoms for less than 1 year) were treated for 2 years with the inhaled corticosteroid (ICS) budesonide (early therapy) or terbutaline. During the third year of the study, terbutaline-treated patients received budesonide (delayed therapy). Differences in lung function and bronchial responsiveness to histamine were observed between the 2 groups. OBJECTIVE: We compared the effects of early versus delayed budesonide therapy after a 10-year follow-up period (13 years after the study began) and current real-life data. METHODS: Of the original 103 patients, 90 were re-examined 13 years after study initiation. After the third year of the study, all patients had their medications, including the dose of ICS, individually adjusted. RESULTS: After the follow-up period, lung function was within the normal range for the entire group (all patients); bronchial responsiveness significantly improved compared with baseline data. No statistically significant differences in clinical or functional variables were found between patients given early or delayed budesonide therapy. However, the delayed therapy group had a higher neutrophil count and higher concentrations of eosinophilic cationic protein and myeloperoxidase in induced sputum. This group had also used more asthma medication and hospital days. CONCLUSIONS: Patients with relatively mild asthma who received ICS within 12 months of their first asthma symptoms or after a 2-year delay achieved equally good functional control of asthma after 10 years of individualized therapy. However, the delayed therapy group exhibited slightly less optimal disease control and more signs of airway inflammation.

Cost-effectiveness analysis of budesonide/formoterol maintenance and reliever therapy versus fixed combination treatments for asthma in Finland*.

BACKGROUND: Budesonide/formoterol maintenance and reliever therapy has shown its effectiveness as a treatment for moderate-to-severe asthma. OBJECTIVE: To explore the cost-effectiveness of budesonide/formoterol maintenance and reliever therapy as compared to fixed combination therapies (budesonide/formoterol and salmeterol/fluticasone) with terbutaline as needed in the treatment of asthma in Finland. METHODS: Patients without asthma exacerbations during a 6-month period were used as the effectiveness variable in the within-trial economic analysis. Finnish unit costs were applied to pooled resource use data, and multinomial cost-effectiveness plane and acceptability curves were formed based on bootstrapping. RESULTS: Use of budesonide/formoterol maintenance and reliever therapy significantly reduced the rate of severe asthma exacerbations as compared with a fixed dose of budesonide/formoterol or salmeterol/fluticasone and terbutaline as needed. Total costs over 6 months were 496 euros per patient for those who used the budesonide/formoterol maintenance and reliever therapy treatment model, which was 78-101 euros lower than the cost of fixed combinations of salmeterol/fluticasone or budesonide/formoterol with terbutaline as needed. The results indicate that the budesonide/formoterol maintenance and reliever therapy achieves a high probability (> 93%) of cost effectiveness irrespective of willingness to pay level. CONCLUSIONS: Budesonide/formoterol maintenance and reliever therapy may be considered in the treatment of moderate-to-severe asthma instead of conventional treatment with combination products in view of its good clinical efficacy and a high probability of cost-effectiveness in the Finnish setting. However, a cost-effectiveness analysis with a longer time horizon, more Finnish-specific data, and ICS + short/long-acting inhaled beta(2)-agonist as an additional comparator is still warranted.