DDW abstract review: Crohn s disease/ibd. Jesse Siffledeen Edmonton. May 26-28, 2017 Fairmont Chateau Lake Louise, Lake Louise, Alberta

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1 DDW abstract review: Crohn s disease/ibd Jesse Siffledeen Edmonton May 26-28, 2017 Fairmont Chateau Lake Louise, Lake Louise, Alberta

2 Disclosure of Commercial Support Potential for conflict(s) of interest: Dr. Siffledeen has not received any payment/funding from a sponsored organization for this presentation.

3 Mitigating Potential Bias Sponsor representatives are not in the planning committee of the program. The planning committee carefully chooses the topics for the program in order to ensure that the principles of scientific integrity, objectivity and balance have been respected. Planning committee chair and members have individual discussions with each speaker regarding expected learning outcomes and teaching format. CME&PD Office provides information sheets and forms to each speaker, communicating the course learning objectives and requirement of scientific integrity, as well as instruction on conflict of interest disclosure and managing bias.

4 Superior endoscopic and deep remission outcomes in adults with moderate-severe Crohn s disease managed with treat-totarget approach versus clinical symptoms: data from CALM Jesse Siffledeen Edmonton May 26-28, 2017 Fairmont Chateau Lake Louise, Lake Louise, Alberta

5 CALM: endoscopic and deep remission with T2T Colombel et al. DDW Aim: to demonstrate that tight control of disease activity using stringent criteria (CDAI, CRP, FCP, & CS use) improves mucosal healing at 56 weeks, as compared to management using less stringent criteria (CDAI & CS use). Methods: subjects had moderate-severe active CD at baseline (based on CDAI, CS use and CDEIS score) and elevated biomarkers (CRP 5, FCP 250). Received step-up in treatment, based on success criteria Primary endpoint: CDEIS < 4 (& no deep ulcers). Secondary endpoints: deep remission (add CDAI<150, no CS after 8 wk, no draining fistulae), biologic remission (FCP<250, CRP<5, CDEIS<4)

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7 CALM: endoscopic and deep remission with T2T Conclusions 1. Tight control (treating to target) leads to superior endoscopic and deep remission 2. This is the first direct evidence of the same Comments 1. With FCP becoming more widely available, these results suggest that it should be routinely measured in CD patients, and acted upon if levels are >250 (dose escalation, or endoscopy/imaging). May 26-28, 2017 Fairmont Chateau Lake Louise, Lake Louise, Alberta

8 Rapidity of onset of response to adalimumab (ADA) in luminal Crohn s disease. Data from the RAPIDA trial Jesse Siffledeen Edmonton May 26-28, 2017 Fairmont Chateau Lake Louise, Lake Louise, Alberta

9 RAPIDA rapidity of onset of response to ADA Marin-Jiminez et al (Mo1773) DDW AIM: multicenter, single arm, open-label study to evaluate the rapidity of onset of clinical response to ADA. Methods: adults with moderate-severe active dz (HBI>8), excluding stricturing and penetrating dz, not responding to conventional Tx (CS +/- IS), received standard adalimumab induction (160/80/40 eow) Endpoints: - HBI response ( 3 pts) evaluated at day 4, week 1. - Clinical remission (HBI <5) assessed at weeks 2, 4, 12 - CRP and FCP assessed at day 4, weeks 1, 2, 4, 12

10 RAPIDA rapidity of onset of response to ADA Results - 80 patients - Response: day 4, wk 1 - Remission: wk 2, wk wk 12 - Median time to response: 4 days (95% CI 0-7) - Median time to response: 7.0 days (4-18) Median CRP levels (mg/l) Median FC levels (µg/g) p-value vs baseline for CRP and FC Baseline Day P< Week P< Week P< Week P<0.0001

11 RAPIDA rapidity of onset of response to ADA Conclusions: 1. ADA promotes rapid clinical response and remission, which can be seen as early as day 4, in CD patients unresponsive to therapy with CS +/- IS. Comments: 1. Response compares with real world data 2. Indirectly supports multimodal induction therapy (drop in remission rates at week 12 may be d/t CS taper). May 26-28, 2017 Fairmont Chateau Lake Louise, Lake Louise, Alberta

12 ARE ANTI-TUMOR NECROSIS FACTORS ASSOCIATED WITH WEIGHT GAIN IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE? Jesse Siffledeen Edmonton May 26-28, 2017 Fairmont Chateau Lake Louise, Lake Louise, Alberta

13 ? Anti-TNF therapy and weight gain Winter R, et al (Sa1966) DDW AIM: a retrospective cohort study that compared weight gain using anti-tnf therapy vs. anti-integrin therapy (vedolizumab) in patients with IBD (both CD and UC) Methods: patients initiating anti-tnf or VDZ between had weight collected at baseline, 3, 6, and 12 months after therapy initiation. Endpoints: 1. Univariate analysis comparing % weight change at time points 2. Linear regression analysis, controlling for disease type (CD or UC), age, gender, smoking status, BL weight, CS use in 1 st 3 months, CRP

14 Results? Anti-TNF therapy and weight gain 301 patients (215 anti-tnf, 86 VDZ)

15 ? Anti-TNF therapy and weight gain Results Univariate analysis: % vs. 2.29% at month 12 (p=0.0091) Multivariate analysis: - anti-tnf associated with significantly more weight gain at 12 months - Β-coeff 3.62 (p=0.02) - Trend to weight gain at 6 months, but not statistically significant - Β-coeff 1.81 (p=0.1)

16 ? Anti-TNF therapy and weight gain Conclusions: 1. Suggests anti-tnf therapy is associated with weight gain over 12 months 2. Overall 7 per cent weight gain over one year Comments: 1. Largest limitation is standardization for objective response to therapy 2. Despite this, a 7 per cent weight gain warrants discussion with patients, who may come to the office already concerned about this possibility. May 26-28, 2017 Fairmont Chateau Lake Louise, Lake Louise, Alberta

17 Exposure to biologic therapy and childhood development among offspring of women with inflammatory bowel disease: results from the PIANO registry Jesse Siffledeen Edmonton May 26-28, 2017 Fairmont Chateau Lake Louise, Lake Louise, Alberta

18 Exposure to biologics and childhood development Roy A, et al (Sa1966) DDW AIM: mulitcenter prospective cohort study assessing offspring development/achievement of milestones in pregnant IBD patients Methods: collected mothers medication exposure, IBD activity, complications in pregnancy, and maternal + infant outcomes for 4 years after delivery. Patients were stratified by drug exposure; group A (IS), group B (biologic), group AB (IS + biologic), controls (IBD mothers w/o exposure to IS or biologic in pregnancy) - Developmental milestones measured by mothers at months 4, 9, 12 (Denver II developmental screening test) and at years 1, 2, 3, 4 (Ages and stages questionnaire).

19 Exposur e Group Outcome # Obs (Exposed) # Obs (Unexposed) Mean Score Ref Mean Score Exposed Delta Score p-value B 12 month DDST AB 12 month commun. ASQ AB 24 month fine motor ASQ AB 48 month commun. ASQ

20 Exposure to biologics and childhood development Results: 1284 women with live births 232 group A, 525 group B, 171 group AB, 356 control group Compared with controls: treatment groups had equal or better achievement of developmental milestones throughout. Incidence of any low-scoring domain on ASQ was low in the study population, and not associated with drug exposure Multivariate analysis: no association b/w developmental delay and drug exposure at year 1 IS OR 0.36 (95% CI ) Biologic OR 0.40 ( ) Combination therapy OR 0.65 ( ) Neuropsychiatric disease rare (seizures 0.9%, autism 0.1%, ADHD 0.2%) Compared with population means: infants exposed to biologics had consistently better achievement of developmental milestones

21 Exposure to biologics and childhood development Conclusions: 1. Large prospective study demonstrating no adverse developmental outcomes in infants exposed to IS +/- biologic therapy in-utero. 2. Infants exposed to biologics had consistently better developmental outcomes as compared with population averages. Comments: 1. Implications for discussion with patients when starting biologics 2. Limitations: does not account for impact of affluence and other SEC factors of population