No Benefit of Concomitant 5-Aminosalicylates in Patients With Ulcerative Colitis Escalated to Biologic Therapy: Pooled Analysis of Individual Participant Data From Clinical Trials

Singh, Siddharth; Proudfoot, James; Dulai, Parambir S.; Jairath, Vipul; Fuméry, Mathurin; Xu, Ronghui; Feagan, Brian G.; Sandborn, William J.

doi:10.1038/s41395-018-0144-2

Cited by 46 publications

(46 citation statements)

References 38 publications

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“…Furthermore, of clinical relevance in this study, it appears that successful discontinuation post‐immunomodulator escalation warrants a more circumspect approach, to ensure that a more durable remission for at least 12 months is achieved prior to stopping the 5‐ASA to ensure a success rate approaching 90% in this cohort. In contrast, rapid discontinuation after escalation to biologics appears feasible in line with the results of the previous studies . Another strength was the median follow‐up period of 27 months in this cohort which was significantly longer than those of previous studies and enabled the evaluation of potential cost savings with a 5‐ASA discontinuation strategy in a per‐patient, real‐world basis.…”

Section: Discussionsupporting

confidence: 63%

“…Indeed, only two previous studies have specifically addressed whether there is additional benefit of 5‐ASA therapy in patients treated with biologics . First, Ungaro et al recently published a nationwide population‐based cohort study across the USA and Denmark which assessed patients newly commenced on anti‐TNF therapy, comparing outcomes in those who remained on 5‐ASA and those who discontinued within 90 days of the commencement of biologic.…”

Section: Discussionmentioning

confidence: 99%

“…There was no significant difference in the proportion of patients requiring new steroid therapy, hospitalisation or surgery between the groups . Secondly, Singh et al examined post‐hoc data from registration trials of infliximab and golimumab and found that the concomitant use of 5‐ASA at the commencement of biologic therapy was not associated with an increased likelihood of clinical response (aOR, 0.89 [0.60‐1.33], P = .58) nor mucosal healing (aOR, 1.12 [0.82‐1.51], P = .48) …”

Section: Discussionmentioning

confidence: 99%

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Aminosalicylate withdrawal following escalation to immunomodulators or biologics in ulcerative colitis: cost saving, convenient and does not compromise efficacy

2020

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Background Aminosalicylates are widely used in ulcerative colitis (UC) and often continued despite treatment escalation, perhaps given a lack of evidence or consensus guiding dose reduction or cessation. The aim was to compare long‐term outcomes in patients who escalated treatment and either continued or discontinued aminosalicylate therapy. Methods Consecutive patients diagnosed with UC ≥1 year prior to escalation to immunomodulator or biologic therapy while concurrently taking aminosalicylates, were compared based on discontinuation versus continuation of aminosalicylates once clinical remission was achieved (denoted as baseline). The primary endpoint was time (from baseline) to treatment failure, defined as requiring steroids, resumption of aminosalicylates or surgery. Successful discontinuation was achieved if no treatment failure occurred throughout follow‐up. The resultant cost savings per patient‐year gleaned by aminosalicylate discontinuation were calculated. Results Of 128 patients meeting inclusion criteria, 71 discontinued and 57 continued aminosalicylates post‐escalation. Median disease duration was 8.2 and 8.7 years (P = .2), time from escalation to baseline 1.8 and 2.9 years (P = .1) respectively. Post‐escalation, median time on immunomodulator was longer, yet no difference in time on biologics was observed, with successful aminosalicylate discontinuation (versus unsuccessful) (2.9 vs 1.2 years (P = .03), 0.4 vs 0.6 years (P = .8) respectively). Kaplan‐Meier survival analysis demonstrated no difference in proportion of treatment failure in the groups post‐baseline (Breslow test, P = .4), yet aminosalicylate discontinuation yielded cost savings of $AUD 2000 per patient‐year. Conclusions These real‐world data support discontinuation of aminosalicylates after achieving remission with either immunomodulator or biologic therapy in UC, at minimal risk of relapse yet enabling significant reductions in cost and tablet burden.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Aminosalicylate withdrawal following escalation to immunomodulators or biologics in ulcerative colitis: cost saving, convenient and does not compromise efficacy

2020

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“…One prior retrospective study did investigate the effect of 5-ASA treatment in patients with IBD with clinically quiescent disease on azathioprine and found no benefit to concomitant 5-ASA in maintaining remission 14. A recent study pooling anti-TNF clinical trial data examined if concomitant 5-ASA treatment at the start of the trial improved outcomes but found no difference among patients on or off 5-ASA 15. This is a related question to our study but is distinct from examining the impact of stopping 5-ASA among patients who were previously on treatment with these agents.…”

Section: Discussionmentioning

confidence: 99%

Stopping 5-aminosalicylates in patients with ulcerative colitis starting biologic therapy does not increase the risk of adverse clinical outcomes: analysis of two nationwide population-based cohorts

Ungaro

Limketkai

Jensen

et al. 2018

Gut

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ObjectiveThe benefit of continuing 5-aminosalicylate (5-ASA) in patients with ulcerative colitis (UC) who initiate anti-tumour necrosis factor-alpha (anti-TNF) biologics is unknown. We aimed to compare clinical outcomes in patients with UC already on 5-ASA who started anti-TNF and then either stopped or continued 5-ASA.DesignOur primary outcome was any adverse clinical event defined as a composite of new corticosteroid use, UC-related hospitalisation or surgery. We used two national databases: the United States (US) Truven MarketScan health claims database and the Danish health registers. Patients with UC who started anti-TNF after having been on oral 5-ASA for at least 90 days were included. Patients were classified as stopping 5-ASA if therapy was discontinued within 90 days of starting anti-TNF. We performed multivariable Cox regression models controlling for demographics, clinical factors and healthcare utilisation. Adjusted HRs (aHR) with 95% CI are reported comparing stopping 5-ASA with continuing 5-ASA.ResultsA total of 3589 patients with UC were included (2890 US and 699 Denmark). Stopping 5-ASA after initiating anti-TNF was not associated with an increased risk of adverse clinical events in the U.S. cohort (aHR 1.04; 95% CI 0.90 to 1.21, p=0.57) nor in the Danish cohort (aHR 1.09; 95% CI 0.80 to 1.49, p=0.60). Results were similar in sensitivity analyses investigating concomitant immunomodulator use and duration of 5-ASA treatment before initiating anti-TNF.ConclusionIn two national databases, stopping 5-ASA in patients with UC starting anti-TNF therapy did not increase the risk of adverse clinical events. These results should be validated in a prospective clinical trial.

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“…Singh et al recently compared the short‐ and intermediate‐term efficacy of continuing vs stopping concomitant aminosalicylates using individual participant data from five RCTS (Active Ulcerative Colitis [ACT]‐1 and ‐2; Program of Ulcerative Colitis Research Studies Utilising an Investigational Treatment [PURSUIT]‐SC, PURSUIT‐M, and NCT00336492) . Among 2183 patients treated with infliximab or golimumab, 78.6% (1715/2183) were on concomitant aminosalicylates.…”

Section: Discussionmentioning

confidence: 99%

Systematic review with meta‐analysis: high prevalence and cost of continued aminosalicylate use in patients with ulcerative colitis escalated to immunosuppressive and biological therapies

Guizzetti

Cipriano

et al. 2018

Aliment Pharmacol Ther

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Summary Background Aminosalicylates are the most frequently prescribed treatment for ulcerative colitis (UC). In the absence of empirical evidence, clinicians are uncertain whether to continue aminosalicylates in patients with UC after escalating therapy. Aims To quantify concomitant aminosalicylate use in UC randomised clinical trials (RCTs), identify factors associated with their use, and estimate treatment costs of concomitant aminosalicylate therapy. Methods MEDLINE, Embase, and CENTRAL were searched from inception to 1 March 2017 for placebo‐controlled RCTs of immunosuppressants, biologics, or oral small molecules in adults with UC. The proportion of patients prescribed concomitant aminosalicylates at trial entry was pooled using a random‐effects model. Meta‐regression was performed to assess trial‐level factors associated with aminosalicylate use. Treatment costs were estimated using 2018 formulary data from five Canadian provinces. Results Thirty‐two trials were included (23 induction only, nine induction, and maintenance trials). The pooled proportion of patients co‐prescribed aminosalicylates was 80.7% (95% CI 75.5%‐85.1%), with considerable observed heterogeneity (I2 = 95%). In univariable meta‐regression, aminosalicylate use was not associated with trial design, setting, year of publication, disease severity, disease duration, or drug class. The estimated direct annual treatment cost of concomitant aminosalicylates is ~$20 million for the Canadian UC population, assuming conservative estimates of UC prevalence, aminosalicylate use and dose, and the lowest cost formulation. Conclusions Approximately 80% of UC patients entering clinical trials of immunosuppressants, biologics, or oral small molecules continue to use aminosalicylates. An RCT is needed to inform the benefits and harms of continuing vs stopping aminosalicylates in patients escalating therapy.

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No Benefit of Concomitant 5-Aminosalicylates in Patients With Ulcerative Colitis Escalated to Biologic Therapy: Pooled Analysis of Individual Participant Data From Clinical Trials

Abstract: Based on IPD pooled analysis, in patients with moderate-severe UC who are escalated to anti-TNF therapy, continuing 5-ASA does not improve clinical outcomes.

Cited by 46 publications

References 38 publications

Aminosalicylate withdrawal following escalation to immunomodulators or biologics in ulcerative colitis: cost saving, convenient and does not compromise efficacy

Aminosalicylate withdrawal following escalation to immunomodulators or biologics in ulcerative colitis: cost saving, convenient and does not compromise efficacy

Stopping 5-aminosalicylates in patients with ulcerative colitis starting biologic therapy does not increase the risk of adverse clinical outcomes: analysis of two nationwide population-based cohorts

Systematic review with meta‐analysis: high prevalence and cost of continued aminosalicylate use in patients with ulcerative colitis escalated to immunosuppressive and biological therapies

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