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Etrolizumab for induction of remission in ulcerative colitis

Overview of attention for article published in Cochrane database of systematic reviews, December 2015
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (80th percentile)
  • Average Attention Score compared to outputs of the same age and source

Mentioned by

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7 tweeters
facebook
1 Facebook page
wikipedia
1 Wikipedia page

Citations

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5 Dimensions

Readers on

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10 Mendeley
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Title
Etrolizumab for induction of remission in ulcerative colitis
Published in
Cochrane database of systematic reviews, December 2015
DOI 10.1002/14651858.cd011661.pub2
Pubmed ID
Authors

Greg Rosenfeld, Claire E Parker, John K MacDonald, Brian Bressler

Abstract

Etrolizumab (rhuMAb beta7) is an anti-integrin that selectively targets the β7 subunits of the α4β7 and αEβ7 integrins, which are involved in the pathogenesis of ulcerative colitis. The objectives of this review were to assess the efficacy and safety of etrolizumab for induction of remission in ulcerative colitis. We searched PubMed, MEDLINE, EMBASE, and the Cochrane Library (CENTRAL) from inception to 12 March 2015. References and conference abstracts were searched to identify additional studies. Randomized controlled trials (RCTs) trials in which etrolizumab was compared to placebo or another active comparator in patients with active ulcerative colitis were included. Two authors independently screened studies for inclusion, assessed methodological quality and extracted data. We assessed methodological quality using the Cochrane risk of bias tool. The primary outcome was failure to induce clinical remission (as defined by the primary studies). Secondary outcomes included failure to induce clinical improvement (as defined by the primary studies), failure to induce endoscopic remission (as defined by the primary studies), adverse events, serious adverse events, withdrawal due to adverse events, and health-related quality of life (as defined by the primary studies). We assessed the overall quality of the evidence using the GRADE criteria. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for each dichotomous outcome. Two RCTs including 172 patients with moderate to severe UC who failed conventional therapy met the inclusion criteria. Both studies were rated as low risk of bias. We did not pool efficacy data from the two included studies due to differences in dose and route of administration. The small phase I study found no statistically significant differences between etrolizumab and placebo in the proportion of patients who failed to enter remission (RR 1.04, 95% CI 1.04 to 1.69; participants = 23) or respond at week 10 (RR 1.67, 95% CI 0.26 to 10.82; participants = 23). The phase II study reported on failure to enter clinical remission at weeks 6 and 10. In the etrolizumab group 91% (71/78) of patients failed to enter remission at week 6 compared to 95% (39/41) of placebo patients (RR 0.96, 95% CI 0.87 to 1.06). Subgroup analysis revealed no statistically significant differences by dose. At week 10, there was a statistically significant difference in clinical remission rates favouring etrolizumab over placebo. Of the patients who received etrolizumab, 85% (66/78) failed to enter remission at week 10 compared to 100% (41/41) patients in the placebo group (RR 0.86, 95% CI 0.77 to 0.95). A subgroup analysis by dose found a statistically significant difference in clinical remission rates favoring 100 mg etrolizumab over placebo (RR 0.81 CI 95% 0.68 to 0.96), but not 300 mg etrolizumab over placebo (RR 0.91, 95% CI 0.80 to 1.03). No significant heterogeneity was detected for this comparison (P = 0.28, I(2) = 13.5%). GRADE analyses indicated that the overall quality of evidence for the clinical remission outcomes was moderate due to sparse data. Both of the included studies reported on safety. The outcome adverse events was initially pooled, however this analysis was removed due to high heterogeneity (I(2) = 88%). The phase I study found no statistically significant difference between etrolizumab and placebo in the proportion of patients who had at least one adverse event. Ninety-five per cent (36/38) of etrolizumab patients had at least one adverse event compared to 100% (10/10) of placebo patients (RR 0.98, 95% CI 0.84 to 1.14). Common adverse events reported in the phase I study included exacerbation of UC, headache, fatigue, abdominal pain, dizziness, nasopharyngitis, nausea, arthralgia and urinary tract infection. There was a statistically significant difference between etrolizumab and placebo in the proportion of patients who had at least one adverse event. Fifty-six per cent (44/78) of etrolizumab patients had at least one adverse event compared to 79% of placebo patients (RR 0.71, 95% CI 0.55 to 0.91). A GRADE analysis indicates that the overall quality of the evidence for this outcome was moderate due to sparse data. Common adverse events reported in the phase II study included worsening UC, nasopharyngitis, nervous system disorders, headache and arthralgia . A pooled analysis of two studies indicates that there was no statistically significant difference in the proportion of patients who had a serious adverse event. Twelve per cent (14/116) of etrolizumab patients had a serious adverse event compared to 12% of placebo patients (6/49) (RR 0.92, 95% CI 0.36 to 2.34). A GRADE analysis indicated that the overall quality of the evidence for this outcome was low due to very sparse data (20 events). Common serious adverse events included worsening of UC, impaired wound healing and bacterial peritonitis. Moderate quality evidence suggests that etrolizumab may be an effective induction therapy for some patients with moderate to severe ulcerative colitis who have failed conventional therapy. Due to small numbers of patients in dose subgroups the optimal dosage of etrolizumab is unclear. Due to sparse data we are uncertain regarding the risk of adverse events and serious adverse events. Further studies are needed to determine the efficacy and safety of etrolizumab in this patient population. There are five ongoing phase III etrolizumab trials and two ongoing open-label extension studies that will provide important new information on the efficacy, safety and optimal dose of this drug for the treatment of UC.

Twitter Demographics

The data shown below were collected from the profiles of 7 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 10 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Chile 1 10%
Netherlands 1 10%
Unknown 8 80%

Demographic breakdown

Readers by professional status Count As %
Student > Master 16 160%
Unspecified 8 80%
Other 7 70%
Researcher 7 70%
Student > Doctoral Student 6 60%
Other 19 190%
Readers by discipline Count As %
Medicine and Dentistry 27 270%
Unspecified 10 100%
Nursing and Health Professions 5 50%
Biochemistry, Genetics and Molecular Biology 4 40%
Pharmacology, Toxicology and Pharmaceutical Science 4 40%
Other 13 130%

Attention Score in Context

This research output has an Altmetric Attention Score of 7. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 February 2019.
All research outputs
#2,330,286
of 13,489,635 outputs
Outputs from Cochrane database of systematic reviews
#5,076
of 10,620 outputs
Outputs of similar age
#68,170
of 357,136 outputs
Outputs of similar age from Cochrane database of systematic reviews
#147
of 223 outputs
Altmetric has tracked 13,489,635 research outputs across all sources so far. Compared to these this one has done well and is in the 82nd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 10,620 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 21.0. This one has gotten more attention than average, scoring higher than 52% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 357,136 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 80% of its contemporaries.
We're also able to compare this research output to 223 others from the same source and published within six weeks on either side of this one. This one is in the 34th percentile – i.e., 34% of its contemporaries scored the same or lower than it.