Ustekinumab Is Associated with Real-World Long-Term Effectiveness and Improved Health-Related Quality of Life in Crohn's Disease.

BACKGROUND: Prospectively and systematically collected long-term real-world clinical data on ustekinumab (anti-interleukin-12/23) are still scarce. AIMS: To assess the long-term effectiveness of ustekinumab in patients with active Crohn's disease (CD). METHODS: This is a prospective multicenter study of adult patients with CD initiating ustekinumab according to recommended doses at 20 Swedish hospitals. The primary outcome was clinical remission (Harvey-Bradshaw Index (HBI) ≤ 4 points) at weeks 52 and 104. Secondary outcomes included clinical response (≥ 3-point-decrease in HBI among patients with initial HBI ≥ 5 points), treatment retention, and biomarkers (C-reactive protein (CRP), hemoglobin, fecal-calprotectin) at weeks 52 and 104 compared to baseline. We also reported Health-related Quality of Life (HRQoL) measures. RESULTS: Of 114 included patients, 107 (94%) had previously failed ≥ 1 and 58 (51%) ≥ 2 anti-tumor necrosis factor agents. Forty (35%) had failed anti-integrin agents. Ustekinumab retention rates at weeks 52 and 104 were 70% (n = 80/114) and 61% (n = 69/114), respectively. Clinical response was seen in 36% (n = 25/69) and 29% (n = 20/69) of the patients, and remission was achieved in 32% (n = 31/96) and 29% (n = 28/96) at weeks 52 and 104, respectively. Median HBI and CRP levels decreased significantly at both timepoints as compared to baseline. Significant improvements were also observed in HRQoL. Adverse events were reported in 11% (n = 13/114) of the patients, including five cases of severe adverse events. No malignancies were observed. CONCLUSIONS: In this nationwide prospective real-world 104-week-follow-up study of adult patients with active CD, ustekinumab was associated with long-term clinical effectiveness and improvement in HRQoL measures when used in routine clinical care.

Prospective observational study on Stelara (ustekinumab) assessing effectiveness in Crohn's disease (PROSE): a 16-week follow-up.

BACKGROUND: Prospectively and systematically collected real-world data on the effectiveness of ustekinumab (anti-interleukin-12/23) for treating Crohn's disease (CD) are still limited. AIM: To assess the short-term real-world effectiveness of ustekinumab in Swedish patients with active CD. METHODS: Prospective multicentre study of adult CD patients initiating ustekinumab according to recommended doses at 20 hospitals, between January 2017 and November 2018. Data were collected through an electronic case report form (eCRF) linked to the Swedish Inflammatory Bowel Disease Registry (SWIBREG). The primary outcomes were clinical response (≥3-point-decrease of Harvey-Bradshaw index (HBI)) and remission (HBI ≤4 points) at week 16. Secondary outcomes included C-reactive protein (CRP) and haemoglobin (Hb) at baseline compared to week 16. RESULTS: Of 114 included patients, 107 (94%) had failed ≥ 1 and 58 (51%) ≥ 2 biological agents (anti-tumour necrosis factor [aTNF] agents or vedolizumab). The 16-week ustekinumab retention rate was 105 (92%). Data on HBI at baseline were available for 96 patients. At week 16, response or remission was achieved in 38/96 (40%) patients (25/96 (26%) achieving clinical remission and 23/96 (24%) showing a clinical response). The median CRP concentration (N = 65) decreased from 6 to 4 mg/l (p = .006). No significant changes in Hb were observed. No incident malignancies or infections, requiring antibiotic treatment, were reported. CONCLUSIONS: In this nation-wide prospective real-world study of adult patients with CD, ustekinumab was associated with clinical effectiveness when administered according to clinical practice and seemed to represent a safe treatment option.

A skewed thiopurine metabolism is a common clinical phenomenon that can be successfully managed with a combination of low-dose azathioprine and allopurinol.

BACKGROUND AND AIMS: A skewed thiopurine metabolism is a phenomenon associated with both poor treatment response and toxicity. Our aim was to evaluate the frequency of this phenomenon and the relationship to thiopurine methyltransferase (TPMT) function. METHODS: All thiopurine metabolite measurements in adult patients (n=4033) between January 2006 and April 2012 were assessed to evaluate the occurrence of a skewed metabolism and the relationship to TPMT genotype and activity. RESULTS: A skewed metabolism was observed in 14% of all patients. It only developed in patients with a normal TPMT genotype, but was observed at all TPMT activity levels within the normal range (9.1-24.2 U/ml RBC). Two cases that illustrate typical clinical scenarios of a skewed metabolism and the effect of combination treatment with low-dose azathioprine and allopurinol are presented. CONCLUSIONS: A skewed metabolism is a common clinical phenomenon in patients with a normal TPMT function, which can develop at all TPMT activity levels within the normal range. We suggest that metabolite measurements should be considered in patients not responding to treatment and in those with hepatotoxicity or myelotoxicity in order to detect a skewed metabolism, since this phenomenon can be successfully managed by a combination of low-dose azathioprine and allopurinol.