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The effectiveness of golimumab in Crohn's disease (CD) is largely unknown as it is not approved for the treatment of the disease. We aimed to identify the population of CD patients treated with golimumab in Sweden, to assess the effectiveness of golimumab (defined as the drug retention rate), and to identify predictors of drug discontinuation.Patients with CD who received at least one injection of golimumab were identified through the Swedish National Quality Registry for Inflammatory Bowel Disease, which includes prospectively collected clinical information. Cox regression models were used to identify predictors of golimumab discontinuation.The study cohort involved 94 patients of whom the majority (96.8%) had previously discontinued at least one anti-tumour necrosis factor (anti-TNF) agent. The drug retention rate at 12 weeks was 85.1%. Predictors of golimumab discontinuation at 12 weeks were previous surgery (adjusted HR = 7.52, 95% CI: 1.12-50.36), concomitant corticosteroid use at baseline (adjusted HR = 5.70, 95% CI: 1.13-28.68) and female sex (adjusted HR = 6.59; 95% CI: 1.04-41.62). The median duration of follow-up was 89 (IQR: 32-158) weeks. The drug retention at the most recent follow-up was 35.1%. Predictors of golimumab discontinuation at the most recent follow-up were corticosteroid use at baseline (adjusted HR = 2.60, 95% CI: 1.17-5.79) and female sex (adjusted HR = 2.24; 95% CI: 1.19-4.23).Patients with CD treated with golimumab were a treatment-refractory group. Despite this, more than one-third of the patients appeared to have had clinical benefit after a median follow-up of more than 1.5 years.

Background Clinical trials may not readily reflect clinical practice. We aimed to assess the clinical effectiveness of vedolizumab in a real-world cohort of patients with ulcerative colitis (UC). Methods This is a prospective, observational, multi-centre cohort study. Eligible patients had active UC confirmed by a Mayo endoscopic subscore ≥2 at initiation of vedolizumab and had started treatment from 1/6/2015. Exclusion criteria included concurrent participation in a clinical trial in which UC treatment is dictated and contraindications to vedolizumab. All patients provided a written consent. Data on clinical characteristics, treatment patterns, disease activity and the short health scale were recorded at baseline and prospectively, using an electronic Case Record Form, integrated with the Swedish National Quality Registry for IBD (SWIBREG). The primary outcomes were A) clinical response, defined as a decrease in partial Mayo score of ≥2 and a reduction of ≥25 % from baseline, with a decrease ≥1 on the rectal bleeding score or an absolute rectal bleeding score of 0 or 1, at week 12 and B) clinical remission, defined as a partial Mayo score Results In total, 117 eligible UC patients were included during the study period 1/6/2015 to 2/6/2018. Clinical and demographical characteristics of patients are shown in Table 1; 101/117 (86%) patients had failed prior anti-TNF therapy. The drug persistence rate was 106/117 (91%) at 12 weeks and 79/117 (68%) at 52 weeks. The clinical response rate at 12 weeks was 59/117 (50%) and the clinical remission rate at 52 weeks was 57/117 (49%). Altogether, 35/117 (30%) had an endoscopic Mayo score ≤1 at 12 weeks and 41/117 (35%) at 52 weeks. However, data on endoscopy were not available for 42 vedolizumab treated patients at 12 weeks and 30 at 52 weeks. Among patients who continued vedolizumab, the median partial Mayo score decreased from 4 (3–5) at baseline to 1 (0–2) at 52 weeks (p < 0.0001). Correspondingly, the median faecal calprotectin decreased from 646 (333–1130) µg/g to 162 (42–382) µg/g (p = 0.0002) and the median C-reactive protein from 5.0 (2.1–8.0) mg/L to 3.5 (1.6–5.0) mg/L (p = 0.008). Consistently, quality of life improved in vedolizumab treated patients, with a significant reduction of the overall short health scale score at 52 weeks (p < 0.0001). Conclusion Vedolizumab treated patients with UC represented a treatment-refractory group. Long-term (52 weeks) effectiveness of vedolizumab can be achieved, in terms of clinical- and inflammatory activity as well as in quality of life. The study was financially supported by Takeda.

ObjectiveThiopurines are used as maintenance therapy in ulcerative colitis (UC), but whether these drugs influence the natural history of the disease is unknown. We aimed to assess the effect of thiopurines in terms of colectomy, hospital admission, progression in disease extent and anti-tumour necrosis factor (TNF) therapy within 10 years from initiation.DesignPatients diagnosed with UC within the Örebro University Hospital catchment area, during 1963–2010, who initiated thiopurines (n=253) were included. To overcome the risk of confounding by indication, we compared patients who stopped treatment within 12 months because of an adverse reaction (n=76) with patients who continued therapy or discontinued due to other reasons (n=177) and assessed long-term outcomes using Cox regression with adjustment for potential confounding factors.ResultsThe cumulative probability of colectomy within 10 years was 19.5% in tolerant patients compared with 29.0% in intolerant (adjusted HR 0.49; 95% CI 0.21 to 0.73). The probability of hospital admission was 34.0% in tolerant versus 56.2% in intolerant patients (adjusted HR 0.36; 95% CI 0.23 to 0.56). The risk for progression in disease extent was 20.4% in tolerant patients compared with 48.8% in intolerant (adjusted HR 0.47; 95% CI 0.21 to 1.06). Within 10 years, 16.1% of tolerant and 27.5% of intolerant patients received anti-TNF therapy (adjusted HR 0.49; 95% CI 0.26 to 0.92).ConclusionBased on the novel approach of comparing patients tolerant and intolerant to thiopurines, we reveal that thiopurines have a profound beneficial impact of the natural history and long-term colectomy rates of UC.

Whether the epidemiology of ulcerative colitis (UC) has changed during recent decades is partly unknown.To depict temporal trends in the epidemiology and medical treatment of UC as well as the long-term risk of progression in disease extent and colectomy, during 1963-2010.Patients were identified by evaluation of all medical records in the archive of the Colitis Clinic, Örebro University Hospital. Comparisons were made between three time periods, 1963-1975, 1976-1990 and 1991-2005.The annual age-standardised incidence increased from 3.5 to 18.5 per 100 000 during the study period (P.01). Correspondingly, the prevalence increased from 44 to 474 per 100 000 between 1965 and 2010. A higher proportion of males than females had extensive colitis at diagnosis (odds ratio: 1.55; 95% CI 1.17-2.05; P.01). The risk for progression in disease extent was 34.5% and 18.5% at 10 years, for patients with proctitis and left-sided colitis, respectively (P.01). The use of 5-aminosalicylates, within 10 years, rise from 79% to 92% between 1963-1975 and 1976-1990 (P.01). Thiopurine use increased from 7% in 1976-1990 to 34% during 1991-2005 (P.01). The colectomy rate at 10 years was 13.5% (95% CI 11.1%-15.8%), and the risk was lower among patients diagnosed in 1991-2005 compared to 1963-1975 (adjusted hazard ratio: 0.61; 95% CI 0.39-0.94; P = .02).The incidence and prevalence of UC increased over time, and the observed prevalence in 2010 is among the highest reported. In parallel, a decrease in colectomy rates was observed during the most recent decades, potentially reflecting improved medical treatment.

Background We aimed to evaluate the effectiveness of tumour necrosis factor antagonist (anti-TNF) compared with vedolizumab (VDZ) as a second-line biological treatment in IBD. Methods A propensity score-matched cohort was created using data from the Swedish National Patient Register, the Swedish Quality Register for IBD (SWIBREG) and the Swedish Prescribed Drug Register. Patients with Crohn’s disease (CD) or ulcerative colitis (UC) exposed to anti-TNF as a first-line biologic, who initiated a second biologic agent 1 May 2014 – 31 December 2016 were included (n = 1363). We compared patients exposed to anti-TNF vs. patients exposed to VDZ as a second-line biologic treatment. The primary outcome was drug continuation rate at 12 months. Secondarily, we assessed survival without hospitalisation (because of IBD, complications of IBD or IBD-related surgery) and survival without IBD-related surgery. Risk of infections was investigated as survival without a) prescription of antibiotics and b) hospitalisation because of infection. Additionally, the proportion of patients on corticosteroids at 12 months was assessed. Results After 1:1 propensity score matching, the cohort was restricted to 400 patients (CD, n = 198; UC, n = 202). For CD, estimated drug continuation rate at 12 months was 72.7% in the VDZ-treated patients, compared with 73.7% in the anti-TNF treated patients (Figure 1A). Survival without IBD-related hospitalisation (81.8% vs. 87.9%, p = 0.25), IBD-related surgery (81.8% vs. 88.9%, p = 0.17), prescription of antibiotics (64.6% vs. 70.7%, p = 0.33) and hospitalisation due to infection (94.9 % vs. 87.9%, p = 0.08) did not significantly differ between the groups. Likewise, there was no statistically significant difference in proportions of patients on corticosteroids at 12 months (21.2% vs. 22.2%, p = 0.86). For UC, estimated drug continuation rate at 12 months was 69.3% in the VDZ-treated patients, compared with 62.4% in the anti-TNF treated patients (Figure 1B). VDZ treated patients had lower survival without IBD-related hospitalisation (82.2% vs. 93.1%, p = 0.02) and IBD-related surgery (82.2% vs. 94.1%, p = 0.01). Survival without antibiotics (81.2% vs. 70.3%, p = 0.08) and hospitalisation due to infection (92.1% vs. 92.1%, p = 0.97) as well as corticosteroid treatment at 12 months (17.8% vs. 23.8%, p = 0.30) did not differ significantly between the groups. Conclusion In this propensity score-matched cohort, the effectiveness and safety of anti-TNF and vedolizumab appear comparable when used as a second-line biologic in CD. In patients with UC, risk of hospitalisation and surgery was lower in patients treated with anti-TNF. Randomised controlled trials are needed to confirm these findings. Support provided by Takeda.

Clinical effectiveness of vedolizumab : Interim analysis of the Swedish observational study on vedolizumab assessing effectiveness and healthcare resource utilisation in patients with ulcerative colitis (SVEAH UC)

Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG-repeat expansion in the huntingtin (IT15) gene. The striatum is one of the regions most affected by neurodegeneration, resulting in the loss of the medium-sized spiny neurons. Traditionally, the large cholinergic striatal interneurons are believed to be spared. Recent studies demonstrate that neuronal dysfunction without cell death also plays an important role in early and mid-stages of the disease. Here, we report that cholinergic transmission is affected in a HD transgenic mouse model (R6/1) and in tissues from HD patients. Stereological analysis shows no loss of cholinergic neurons in the striatum or septum in R6/1 mice. In contrast, the levels of mRNA and protein for vesicular acetylcholine transporter (VAChT) and choline acetyltransferase (ChAT) are decreased in the striatum and cortex, and acetylcholine esterase activity is lowered in the striatum of R6/1 mice already at young ages. Accordingly, VAChT is also reduced in striatal tissue from patients with HD. The decrease of VAChT in the patient samples studied is restricted to the striatum and does not occur in the hippocampus or the spinal cord. The expression and localization of REST/NRSF, a transcriptional regulator for the VAChT and ChAT genes, are not altered in cholinergic neurons. We show that the R6/1 mice exhibit severe deficits in learning and reference memory. Taken together, our data show that the cholinergic system is dysfunctional in R6/1 and HD patients. Consequently, they provide a rationale for testing of pro-cholinergic drugs in this disease.

A Swedish observational study (SVEAH) on vedolizumab assessing effectiveness and healthcare resource utilization in patients with inflammatory bowel disease

The impact of thiopurine drugs on the natural history and surgical outcome of ulcerative colitis : A cohort study