Clinical, endoscopic and radiographic outcomes with ustekinumab in medically-refractory Crohn's disease: real world experience from a multicentre cohort.

BACKGROUND: Ustekinumab is a monoclonal antibody targeting interleukins-12 and -23, with efficacy in Crohn's disease (CD) demonstrated in clinical trials. AIM: To assess the real-world clinical, endoscopic and radiographic response and remission outcomes achieved with ustekinumab in medically-refractory CD. METHODS: A retrospective multicentre cohort study was performed on CD patients receiving ustekinumab between 2011 and 2016. The primary outcome was achievement of clinical and objective steroid-free response and remission at 3, 6 and 12 months. Clinical response and remission were defined by reduction in Harvey Bradshaw Index (HBI) of ≥3 points and an HBI ≤4 points respectively. Objective response was defined by improvement in endoscopic or radiographic CD, as assessed by ileocolonoscopy, contrast-enhanced ultrasound or CT/MR enterography. Objective remission was defined by endoscopic mucosal healing or complete resolution of inflammatory parameters on radiographic assessment. RESULTS: A total of 167 CD patients were treated with ustekinumab. 95.2% (159/167) previously failed anti-TNF therapy. Median follow-up was 45.6 weeks (IQR: 24.4-88.9). At 3 months, clinical response was achieved in 38.9% (65/167) and remission in 15.0% (25/167) of patients. At 6 months, clinical response was achieved in 60.3% (91/151) and remission in 25.2% (38/151) of patients. At 12 months, clinical response was achieved in 59.5% (66/111) and remission in 27.9% (31/111) of patients. Endoscopic or radiographic response was demonstrated in 54.5% (67/123) at 6 months and 55.8% (48/86) of patients at 12 months. CONCLUSIONS: Ustekinumab is an effective therapeutic option for inducing and maintaining clinical, endoscopic and radiographic response in patients with Crohn's disease failing anti-TNF therapy.

Adalimumab dose escalation is effective for managing secondary loss of response in Crohn's disease.

BACKGROUND: The efficacy of adalimumab in maintaining remission in Crohn's disease patients may wane over time, leading to secondary loss of response that is often managed with dose escalation. However, the response to adalimumab dose escalation and long-term outcomes after escalation have not been well evaluated. AIMS: To characterise the short- and long-term clinical responses to adalimumab dose escalation for secondary loss of response. METHODS: A retrospective cohort study evaluating Crohn's disease out-patients requiring adalimumab dose escalation for secondary loss of response from 2003 to 2013 was conducted. The primary outcome was the proportion of patients achieving symptomatic clinical response to dose escalation and subsequent development of tertiary loss of response. Duration of regained response was assessed by Kaplan-Meier analysis. RESULTS: Ninety-two CD patients met inclusion criteria with mean duration of follow-up of 170.2 weeks (±129.6 weeks). Disease distribution was predominantly ileal (37/92, 40.2%) or ileocolonic (43/92, 46.7%), with equal distribution of inflammatory (34.8%), stricturing (27.2%), and penetrating (38.0%) disease phenotypes. At 24 weeks post-dose escalation, 74/92 (80.4%) patients had symptomatic clinical response. Among responders, median duration of sustained response was 69.2 weeks (IQR 29.4-107.1) but 42/74 (56.8%) responders experienced subsequent tertiary loss of response at a median time of 47.9 weeks (IQR 24.7-80.3). C-reactive protein >10.0 mg/L at the time of dose escalation predicted tertiary loss of response in univariate analysis (OR 3.32, 95% CI: 1.18-9.37). CONCLUSIONS: In patients with Crohn's disease, adalimumab dose escalation is effective for recapturing symptomatic response after secondary loss of response, but more than half will eventually experience a tertiary loss of response.

The incidence rate of colectomy for medically refractory ulcerative colitis has declined in parallel with increasing anti-TNF use: a time-trend study.

BACKGROUND: Medical therapy is standard treatment for ulcerative colitis with colectomy reserved for medically refractory disease or malignancy. The introductions of ciclosporin in 1994 and anti-TNF therapy in 2005 have extended medical management options. AIM: To determine whether the colectomy incidence rate for medically refractory ulcerative colitis has changed since the introduction of anti-TNF therapy. METHODS: Adult patients with a diagnosis of ulcerative colitis and who subsequently underwent an urgent or elective colectomy for medically refractory disease in Edmonton, Canada between 1 January 1998 and 31 December 2011 were identified. Log-linear regression was used to estimate the annual percent change in the total colectomy incidence rate (urgent and elective combined) and the urgent and elective incidence rates individually, before and after 2005, the year infliximab was approved for use in ulcerative colitis. Temporal trends of drug utilisation in this study population were also described. RESULTS: During 1998-2011, 481 patients with ulcerative colitis underwent a colectomy for medically refractory disease. There was negligible change in the total colectomy incidence rate from 1998 to 2005, with an annual percent change of 4.4% (95% confidence interval (CI): -1.12% to 10.16%). From 2005-2011, following the approval and increasing use of anti-TNF therapy, the total colectomy incidence rate decreased by 16.1% (95% CI: -21.32% to -10.54%) every year to 0.9 per 100 ulcerative colitis patients in 2011. CONCLUSION: The total incidence rate of colectomy for medically refractory ulcerative colitis has declined substantially since 2005, paralleling the increased use of anti-TNF therapy in this patient population.

Treatment of ulcerative colitis with adalimumab or infliximab: long-term follow-up of a single-centre cohort.

Aliment Pharmacol Ther 2010; 32: 522-528 Summary Background Randomized, controlled trials have demonstrated that anti-TNF agents are efficacious in inducing remission in cases of Crohn's disease and ulcerative colitis. However, response rates for anti-TNF agents in 'real life' clinical practice are less well-defined. Aims To examine the response rates and long-term outcomes of infliximab and adalimumab treatment for out-patients with ulcerative colitis and to study the variables associated with response rates. Methods In a prospective study, a single-centre out-patient cohort was treated and followed up according to a structured protocol of clinical care. Response to treatment was assessed using a physician's global assessment that focused on normalization of bowel frequency, absence of blood with defecation and tapering of corticosteroids to zero. Results Fifty-three ulcerative colitis patients were included in the study. Responses to induction therapy were 96.4% (27/28) for infliximab and 80% (20/25) for adalimumab (P = 0.0889). Responses to maintenance therapy were similar: infliximab 77.8% (14/18) and adalimumab 70.0% (14/20) (P = 0.7190). Multivariate analyses of the induction and maintenance responses did not reveal confounding elements. No new safety signals were identified. Conclusions This long-term follow-up of a single-centre cohort of ulcerative colitis patients demonstrates that 'real-life' out-patient treatment with infliximab and adalimumab is effective in induction and maintenance of response.

Video-capture teleradiology for the after-hours reading of computerized tomography scans.

We evaluated the after-hours support that radiologists could provide from their homes to an urban hospital for reading emergency computerized tomography (CT) scans. During a six-month study period, 36 CT scans were acquired using a video-capture card in a PC and transmitted via an ordinary telephone line. The teleradiology interpretation and the formal report (from the hard copy) were compared with a reference or gold standard interpretation made by a radiologist and an emergency physician for 31 of the 36 cases. In comparison with the gold standard, there were 26 correct diagnoses by teleradiology (84%) and five incorrect (16%). Head CT scans accounted for 74% of the transmitted scans and all five of the cases with discrepant diagnoses. The cause of the single clinically relevant discrepancy was found to be unrelated to the use of teleradiology. In comparison with the formal report, the accuracy of the teleradiologist was not significantly different for all categories combined or for head CT scans alone. Video-capture technology provided a reliable means of transmitting CT scans for after-hours interpretation in emergency cases.