A Retrospective Multicentric Belgian Observational Trial to Evaluate the Successfulness of Adalimumab Dose Escalation and De-escalation in Patients With Moderate-to-severe Ulcerative Colitis Treated With Adalimumab
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 231
- 试验地点
- 1
- 主要终点
- The need and success of adalimumab dose escalation from 40mg every other week to 40mg every week in patients with moderate-to-severe ulcerative colitis during adalimumab treatment
研究概览
简要总结
This retrospective multi-centric Belgian observational trial will involve all patients who have initiated adalimumab for moderate-to-severe ulcerative colitis prior to September 1st 2015 in a Belgian centre maintaining a prospective log of patients using biological therapy.
Only patients fulfilling all Belgian reimbursement criteria for adalimumab will be included, namely having failed mesalamine and steroids or thiopurine analogues for at least 3 months, or being intolerant to this therapy, and showing a total Mayo score of at least 6 with an endoscopic sub-score of at least 2.
Both short-term and long-term outcome of adalimumab therapy will be evaluated, focusing on the need and successfulness of adalimumab dose-escalation from 40mg every other week to 40mg every week, and dose de-escalation back to 40mg every other week.
详细描述
Adalimumab is approved for the treatment of moderate to severe ulcerative colitis after failure of aminosalicylates plus corticosteroids and/or immunomodulators.1-4 In the registration studies for adalimumab in ulcerative colitis prior anti-tumor necrosis factor (TNF) treatment was restricted; in ULTRA 1, prior anti-TNF treatment was an exclusion criterion,5 while in ULTRA 2, 40% of patients had been exposed to infliximab prior to start of adalimumab, but primary non-responders to infliximab were excluded.6 Open label real life studies have shown good responses to adalimumab in UC. However typically, these cohorts were small and most patients were anti-TNF naïve. One Italian open label study on 88 patients reported clinical remission rates of 28% and 43% at week 12 and year 1, respectively.7 No significant differences were observed between infliximab naïve and infliximab exposed UC patients. In a Belgian open label study of 73 patients previously failing infliximab, overall clinical response at week 12 and 52 were 75% and 52%, respectively.8 Adalimumab was continued without need for dose escalation throughout year 1 in 16 patients, 22 needed dose escalation and 35 discontinued treatment within 1 year. Prior response to infliximab and early serum concentrations correlated with response.
While data are available in Crohn's disease,9 real life data on adalimumab dose escalation and dose de-escalation are limited in ulcerative colitis. Similarly, factors associated with need and success of dose escalation and dose de-escalation later on are almost absent.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age at least 18 at initiation of adalimumab therapy
- •Adalimumab initiated before September 1st 2015
- •Established diagnosis of ulcerative colitis
- •Having failed mesalamine and steroids or thiopurine analogues for at least 3 months, or being intolerant to this therapy (as described in the Belgian reimbursement criteria)
- •Active ulcerative colitis as described in the Belgian reimbursement criteria, namely showing a total Mayo score of at least 6 with an endoscopic sub-score of at least 2
排除标准
- •Subjects with Crohn's disease or inflammatory bowel disease (IBD) type unclassified
- •Subjects previously treated with adalimumab
- •Subjects treated with adalimumab for other reasons than moderate-to-severe ulcerative colitis, including extra-intestinal manifestations and pre-emptively switch from other biological therapies (i.e. while being in clinical remission)
- •Subjects who underwent subtotal colectomy or proctocolectomy prior to adalimumab initiation
结局指标
主要结局
The need and success of adalimumab dose escalation from 40mg every other week to 40mg every week in patients with moderate-to-severe ulcerative colitis during adalimumab treatment
时间窗: Through study completion, an average of 24 months
The proportion of patients requiring dose-escalation from adalimumab 40mg every other week to 40mg every week and the success rate of this intervention. Success of dose-escalation is defined based on a positive physician global assessment and absence of blood on two consecutive visits at least 3 months apart from each other. Of note: patients requiring a second intervention later on (addition of any type of steroids, addition of any immunomodulatory drug or optimization to off-label adalimumab 80 mg every week) will be regarded as failure (treatment optimization based on trough level monitoring or biomarkers alone will not be included)
次要结局
- Safety of adalimumab: Proportion of patients developing (serious) adverse events under adalimumab therapy during adalimumab treatment(Through study completion, an average of 24 months)
- Short-term (steroid-free) clinical remission response to adalimumab in patients with moderate-to-severe ulcerative colitis(Week 8)
- Short-term (steroid-free) clinical benefit to adalimumab in patients with moderate-to-severe ulcerative colitis(Week 8)
- Short-term (steroid-free) mucosal healing under adalimumab in patients with moderate-to-severe ulcerative colitis(Week 8)
- UC related hospitalization during adalimumab treatment(Through study completion, an average of 24 months)
- Adalimumab dose-escalation free survival during adalimumab treatment(Through study completion, an average of 24 months)
- Adalimumab dose de-escalation free survival during adalimumab treatment(Through study completion, an average of 24 months)
- Success of dose de-escalation within 6 months after dose de-escalation(Through study completion, an average of 24 months)
- Identification of variables associated with short-term outcome(Week 8)
- Short-term (steroid-free) clinical response response to adalimumab in patients with moderate-to-severe ulcerative colitis(Week 8)
- Short-term (steroid-free) complete mucosal healing under adalimumab in patients with moderate-to-severe ulcerative colitis(Week 8)
- Identification of baseline variables associated with successful dose-escalation(Through study completion, an average of 24 months)
- Short-term (steroid-free) biological response to adalimumab in patients with moderate-to-severe ulcerative colitis(Week 8)
- UC related colectomy during follow-up(Through study completion, an average of 24 months)
- Identification of baseline variables associated with need for dose-escalation(Through study completion, an average of 24 months)