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Withdrawal of immunosuppressant or biologic therapy for patients with quiescent Crohn's disease

Overview of attention for article published in Cochrane database of systematic reviews, May 2018
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  • Above-average Attention Score compared to outputs of the same age (62nd percentile)

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Title
Withdrawal of immunosuppressant or biologic therapy for patients with quiescent Crohn's disease
Published in
Cochrane database of systematic reviews, May 2018
DOI 10.1002/14651858.cd012540.pub2
Pubmed ID
Authors

Ray K Boyapati, Joana Torres, Carolina Palmela, Claire E Parker, Orli M Silverberg, Sonam D Upadhyaya, Tran M Nguyen, Jean-Frédéric Colombel

Abstract

Crohn's disease (CD) is a chronic, relapsing and remitting disease of the gastrointestinal tract that can cause significant morbidity and disability. Current treatment guidelines recommend early intervention with immunosuppressant or biological therapy in high-risk patients with a severe disease phenotype at presentation. The feasibility of therapeutic de-escalation once remission is achieved is a commonly encountered question in clinical practice, driven by patient and clinician concerns regarding safety, adverse events, cost and national regulations. Withdrawal of immunosuppressant and biologic drugs in patients with quiescent CD may limit adverse events and reduce healthcare costs. Alternatively, stopping these drug therapies may result in negative outcomes such as disease relapse, drug desensitization, bowel damage and need for surgery. To assess the feasibility and safety of discontinuing immunosuppressant or biologic drugs, administered alone or in combination, in patients with quiescent CD. We searched CENTRAL, MEDLINE, Embase and the Cochrane IBD Group Specialized Register from inception to 19 December 2017. We also searched the reference lists of potentially relevant manuscripts and conference proceedings to identify additional studies. Randomized controlled trials (RCTs) and prospective cohort studies that followed patients for a minimum duration of six months after drug discontinuation were considered for inclusion. The patient population of interest was adults (> 18 years) with CD (as defined by conventional clinical, endoscopic or histologic criteria) who had achieved remission while receiving immunosuppressant or biologic drugs administered alone or in combination. Patients then discontinued the drug regimen following a period of maintenance therapy of at least six months. The comparison was usual care (i.e. continuation of the drug regimen). The primary outcome measure was the proportion of patients who relapsed following discontinuation of immunosuppressant or biologic drugs, administered alone or in combination. Secondary outcomes included: the proportion of patients who responded to the reintroduction of immunosuppressant or biologic drugs, given as monotherapy or combination therapy; the proportion of patients who required surgery following relapse; the proportion of patients who required hospitalization for CD following relapse; the proportion of patients who developed new CD-related complications (e.g. fistula, abscesses, strictures) following relapse; the proportion of patients with elevated biomarkers of inflammation (CRP, fecal calprotectin) in those who stop and those who continue therapy; the proportion of patients with anti-drug antibodies and low serum trough drug levels; time to relapse; and the proportion of patients with adverse events, serious adverse events and withdrawal due to adverse events. For dichotomous outcomes, we calculated the risk ratio (RR) and 95% confidence interval (95% CI). Data were analyzed on an intention-to-treat basis where patients with missing outcome data were assumed to have relapsed. The overall quality of the evidence supporting the primary and secondary outcomes was assessed using the GRADE criteria. A total of six RCTs (326 patients) evaluating therapeutic discontinuation in patients with quiescent CD were eligible for inclusion. In four RCTs azathioprine monotherapy was discontinued, and in two RCTs azathioprine was discontinued from a combination therapy regimen consisting of azathioprine with infliximab. No studies of biologic monotherapy withdrawal were eligible for inclusion. The majority of studies received unclear or low risk of bias ratings, with the exception of three open-label RCTs, which were rated as high risk of bias for blinding. Four RCTs (215 participants) compared discontinuation to continuation of azathioprine monotherapy, while two studies (125 participants) compared discontinuation of azathioprine from a combination regimen to continuation of combination therapy. Continuation of azathioprine monotherapy was shown to be superior to withdrawal for risk of clinical relapse. Thirty-two per cent (36/111) of azathioprine withdrawal participants relapsed compared to 14% (14/104) of participants who continued with azathioprine therapy (RR 0.42, 95% CI 0.24 to 0.72, GRADE low quality evidence). However, it is uncertain if there are any between-group differences in new CD-related complications (RR 0.34, 95% CI 0.06 to 2.08, GRADE low quality evidence), adverse events (RR 0.88, 95% CI 0.67 to 1.17, GRADE low quality evidence), serious adverse events (RR 3.29, 95% CI 0.35 to 30.80, GRADE low quality evidence) or withdrawal due to adverse events (RR 2.59, 95% CI 0.35 to 19.04, GRADE low quality evidence). Common adverse events included infections, mild leukopenia, abdominal symptoms, arthralgias, headache and elevated liver enzymes. No differences between azathioprine withdrawal from combination therapy versus continuation of combination therapy were observed for clinical relapse. Among patients who continued combination therapy with azathioprine and infliximab, 48% (27/56) had a clinical relapse compared to 49% (27/55) of patients discontinued azathioprine but remained on infliximab (RR 1.02, 95% CI 0.68 to 1.52, P = 0.32; GRADE low quality evidence). The effects on adverse events (RR 1.11, 95% CI 0.44 to 2.81, GRADE low quality of evidence) or serious adverse events are uncertain (RR 1.00, 95% CI 0.21 to 4.66; GRADE very low quality of evidence). Common adverse events in the combination therapy studies included infections, liver test elevations, arthralgias and infusion reactions. The effects of withdrawal of immunosuppressant therapy in people with quiescent Crohn's disease are uncertain. Low quality evidence suggests that continuing azathioprine monotherapy may be superior to withdrawal for avoiding clinical relapse, while very low quality evidence suggests that there may be no difference in clinical relapse rates between discontinuing azathioprine from a combination therapy regimen, compared to continuing combination therapy. It is unclear whether withdrawal of azathioprine, initially administered alone or in combination, impacts on the development of CD-related complications, adverse events, serious adverse events or withdrawal due to adverse events. Further high-quality research is needed in this area, particularly double-blind RCTs in which biologic therapy or an immunosuppressant other than azathioprine is withdrawn.

Twitter Demographics

The data shown below were collected from the profiles of 6 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 115 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 115 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 24 21%
Student > Master 16 14%
Student > Bachelor 11 10%
Student > Ph. D. Student 11 10%
Student > Postgraduate 8 7%
Other 20 17%
Unknown 25 22%
Readers by discipline Count As %
Medicine and Dentistry 50 43%
Nursing and Health Professions 8 7%
Social Sciences 7 6%
Pharmacology, Toxicology and Pharmaceutical Science 5 4%
Biochemistry, Genetics and Molecular Biology 4 3%
Other 13 11%
Unknown 28 24%

Attention Score in Context

This research output has an Altmetric Attention Score of 4. 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 30 July 2018.
All research outputs
#3,914,403
of 13,304,005 outputs
Outputs from Cochrane database of systematic reviews
#6,968
of 10,548 outputs
Outputs of similar age
#101,414
of 271,141 outputs
Outputs of similar age from Cochrane database of systematic reviews
#141
of 175 outputs
Altmetric has tracked 13,304,005 research outputs across all sources so far. This one has received more attention than most of these and is in the 70th percentile.
So far Altmetric has tracked 10,548 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 20.8. This one is in the 33rd percentile – i.e., 33% of its peers scored the same or lower than it.
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 271,141 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 62% of its contemporaries.
We're also able to compare this research output to 175 others from the same source and published within six weeks on either side of this one. This one is in the 19th percentile – i.e., 19% of its contemporaries scored the same or lower than it.