Everolimus does not further reduce polycystic liver volume when added to long acting octreotide: Results from a randomized controlled trial

Chrispijn, Melissa; Gevers, Tom J.G.; Hol, Jeroen; Monshouwer, R.; Dekker, Helena M.; Drenth, Joost P.H.

doi:10.1016/j.jhep.2013.03.004

Cited by 73 publications

(62 citation statements)

References 21 publications

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“…3,[18][19][20][21][22][23] Five of these (three RCTs 3,18,19 and two further subsequent publications) 20,21 investigated the role somatostatin analogues ( Table 2). The remaining two studies (one RCT 22 and one case series) 23 investigated the role of mTOR inhibitors ( Table 3). The RCTs investigating the role of somatostatin analogues were small but well designed.…”

Section: Resultsmentioning

confidence: 99%

“…20 Only one RCT examined the influence of mTOR inhibitors. 22 This trial randomised 44 patients to either 48 weeks of everolimus daily combined with octreotide every 4 weeks or to octreotide monotherapy.…”

Section: Resultsmentioning

confidence: 99%

“…22 It randomised 44 patients either to dual therapy of everolimus and octreotide or to monotherapy with octreotide. Liver volume reduced by 3.5% and 3.8% in the control and intervention groups respectively.…”

Section: Efficacy Of Somatostatin Analogues and Mtor Inhibitorsmentioning

confidence: 99%

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Medical therapy for polycystic liver disease

Khan

Dennison

Garcea

2016

annals

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Introduction Somatostatin analogues and rapamycin inhibitors are two classes of drugs available for the management of polycystic liver disease but their overall impact is not clearly established. This article systematically reviews the literature on the medical management of polycystic liver disease. The outcomes assessed include reduction in liver volume and the impact on quality of life. Methods The English language literature published between 1966 and August 2014 was reviewed from a MEDLINE®, PubMed, Embase™ and Cochrane Library search. Search terms included ‘polycystic’, ‘liver’, ‘sirolimus’, ‘everolimus’, ‘PCLD’, ‘somatostatin’, ‘octreotide’, ‘lanreotide’ and ‘rapamycin’. Both randomised trials and controlled studies were included. References of the articles retrieved were also searched to identify any further eligible publications. The studies included were appraised using the Jadad score. Results Seven studies were included in the final review. Five studies, of which three were randomised trials, investigated the role of somatostatin analogues and the results showed a mean reduction in liver volume ranging from 2.9% at six months to 4.95 ±6.77% at one year. Only one randomised study examined the influence of rapamycin inhibitors. This trial compared dual therapy with everolimus and octreotide versus octreotide monotherapy. Liver volume reduced by 3.5% and 3.8% in the control and intervention groups respectively but no statistical difference was found between the two groups (p=0.73). Two randomised trials investigating somatostatin analogues assessed quality of life using SF-36®. Only one subdomain score improved in one of the trials while two subdomain scores improved in the other with somatostatin analogue therapy. Conclusions Somatostatin analogues significantly reduce liver volumes after six months of therapy but have only a modest improvement on quality of life. Rapamycin inhibitors do not confer any additional advantage.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Medical therapy for polycystic liver disease

Khan

Dennison

Garcea

2016

annals

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“…In addition, based on our previous observations, we also hypothesized that a reduction of ≥120mL in LV after 6 months of SA-treatment results in a more pronounced effect on the perceived complaints [12]. …”

Section: Responsivenessmentioning

confidence: 95%

“…In addition, we recently demonstrated that a reduction of ≥120mL in liver volume after 6 months has a high positive predictive value of improving complaints, a reduction which lies above the 95% upper limit of the confidence intervals of the differences in LV assessed by two software methods measuring the same LV [11]. Also mTOR inhibitors might reduce liver volume, although the data are less robust and combination of octreotide and everolimus did not increase the LV reducing effect of octreotide alone [3,12].…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a polycystic liver disease complaint-specific assessment (POLCA)

Temmerman

Dobbels

et al. 2014

Journal of Hepatology

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Effect of Lanreotide on Kidney Function in Patients With Autosomal Dominant Polycystic Kidney Disease

Meijer

Visser

Aerts

et al. 2018

JAMA

101

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IMPORTANCE Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst formation in both kidneys and loss of renal function, eventually leading to a need for kidney replacement therapy. There are limited therapeutic management options. OBJECTIVE To examine the effect of the somatostatin analogue lanreotide on the rate of kidney function loss in patients with later-stage ADPKD. DESIGN, SETTING, AND PARTICIPANTS An open-label randomized clinical trial with blinded end point assessment that included 309 patients with ADPKD from July 2012 to March 2015 at 4 nephrology outpatient clinics in the Netherlands. Eligible patients were 18 to 60 years of age and had an estimated glomerular filtration rate (eGFR) of 30 to 60 mL/min/1.73 m 2. Follow-up of the 2.5-year trial ended in August 2017. INTERVENTIONS Patients were randomized to receive either lanreotide (120 mg subcutaneously once every 4 weeks) in addition to standard care (n = 153) or standard care only (target blood pressure <140/90 mm Hg; n = 152). MAIN OUTCOMES AND MEASURES Primary outcome was annual change in eGFR assessed as slope through eGFR values during the 2.5-year treatment phase. Secondary outcomes included change in eGFR before vs after treatment, incidence of worsening kidney function (start of dialysis or 30% decrease in eGFR), change in total kidney volume and change in quality of life (range: 1 [not bothered] to 5 [extremely bothered]). RESULTS Among the 309 patients who were randomized (mean [SD] age, 48.4 [7.3] years; 53.4% women), 261 (85.6%) completed the trial. Annual rate of eGFR decline for the lanreotide vs the control group was −3.53 vs −3.46 mL/min/1.73 m 2 per year (difference, −0.08 [95% CI, −0.71 to 0.56]; P = .81). There were no significant differences for incidence of worsening kidney function (hazard ratio, 0.87 [95% CI, 0.49 to 1.52]; P = .87), change in eGFR (−3.58 vs −3.45; difference, −0.13 mL/min/1.73 m 2 per year [95% CI, −1.76 to 1.50]; P = .88), and change in quality of life (0.05 vs 0.07; difference, −0.03 units per year [95% CI, −0.13 to 0.08]; P = .67). The rate of growth in total kidney volume was lower in the lanreotide group than the control group (4.15% vs 5.56%; difference, −1.33% per year [95% CI, −2.41% to −0.24%]; P = .02). Adverse events in the lanreotide vs control group included injection site discomfort (32% vs 0.7%), injection site papule (5.9% vs 0%), loose stools (91% vs 6.6%), abdominal discomfort (79% vs 20%), and hepatic cyst infections (5.2% vs 0%). CONCLUSIONS AND RELEVANCE Among patients with later-stage autosomal dominant polycystic kidney disease, treatment with lanreotide compared with standard care did not slow the decline in kidney function over 2.5 years of follow-up. These findings do not support the use of lanreotide for treatment of later-stage autosomal dominant polycystic kidney disease.

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Everolimus does not further reduce polycystic liver volume when added to long acting octreotide: Results from a randomized controlled trial

Cited by 73 publications

References 21 publications

Medical therapy for polycystic liver disease

Medical therapy for polycystic liver disease

Development and validation of a polycystic liver disease complaint-specific assessment (POLCA)

Effect of Lanreotide on Kidney Function in Patients With Autosomal Dominant Polycystic Kidney Disease

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