Comparative efficacy and safety of treatments for secondary Raynaud's phenomenon: a systematic review and network meta-analysis of randomised trials.

Journal

The Lancet. Rheumatology
ISSN: 2665-9913
Titre abrégé: Lancet Rheumatol
Pays: England
ID NLM: 101765308

Informations de publication

Date de publication:
Dec 2019
Historique:
received: 28 08 2019
revised: 04 10 2019
accepted: 07 10 2019
medline: 1 12 2019
pubmed: 1 12 2019
entrez: 17 1 2024
Statut: ppublish

Résumé

Several pharmacological treatments are available for secondary Raynaud's phenomenon, but there is uncertainty regarding the best options. We aimed to assess and compare the benefits and harms of treatments available for secondary Raynaud's phenomenon. We did a systematic review and network meta-analysis of randomised controlled trials (RCTs) of pharmacological treatments. We searched for systematic reviews published in MEDLINE and the Cochrane Database of Systematic Reviews up to Jan 31, 2017, and for RCTs published from inception to Sept 24, 2019 in MEDLINE, Embase, and ClinicalTrials.gov. We included double-blind RCTs (parallel or crossover) that compared two or more pharmacological treatments or placebo in patients with secondary Raynaud's phenomenon. Individual patient data were obtained for one unpublished RCT. Three researchers independently screened the texts and extracted the data. Efficacy outcomes included severity (on a ten-point scale), daily frequency, and mean duration of Raynaud's phenomenon attacks. We also examined tolerability and acceptability. Pairwise meta-analyses and Bayesian random-effects network meta-analyses were used to synthesise data. This study is registered with PROSPERO (CRD42017057518). We included 58 RCTs in the analysis, comprising 3867 patients (3540 [91·5%] with secondary Raynaud's phenomenon) and 15 classes of drugs. Phosphodiesterase 5 (PDE5) inhibitors were more effective than placebo for frequency (mean difference -0·36 [95% credibility interval -0·69 to -0·04]), severity (-0·34 [-0·66 to -0·03]), and duration (-3·42 [-6·62 to -0·29]) of attacks (low to moderate level of evidence). Calcium channel blockers (CCBs) were superior to placebo for frequency (-0·35 [-0·67 to -0·02]) and severity (-0·84 [-1·25 to -0·45]) of attacks (low level of evidence). For severity of attacks, selective serotonin-reuptake inhibitors (-1·54 [-2·68 to -0·41]; very low level of evidence) and oral prostacyclin receptor agonists (-0·48 [-0·80 to -0·16]; low level of evidence) were superior to placebo. No other drug classes were significantly superior to placebo with regard to efficacy outcomes. Compared with placebo, tolerability was lower for PDE5 inhibitors (incidence rate ratio for serious adverse events or early study exit due to adverse events 3·30 [95% CrI 1·49 to 7·55]) and CCBs (3·13 [1·33 to 7·04]). For all outcomes, global heterogeneity and between-study variance ranged from low (I PDE5 inhibitors and CCBs are the most effective pharmacological options, albeit with moderate efficacy and a low level of evidence. Current evidence does not support the use of any other drug in secondary Raynaud's phenomenon. None.

Sections du résumé

BACKGROUND BACKGROUND
Several pharmacological treatments are available for secondary Raynaud's phenomenon, but there is uncertainty regarding the best options. We aimed to assess and compare the benefits and harms of treatments available for secondary Raynaud's phenomenon.
METHOD METHODS
We did a systematic review and network meta-analysis of randomised controlled trials (RCTs) of pharmacological treatments. We searched for systematic reviews published in MEDLINE and the Cochrane Database of Systematic Reviews up to Jan 31, 2017, and for RCTs published from inception to Sept 24, 2019 in MEDLINE, Embase, and ClinicalTrials.gov. We included double-blind RCTs (parallel or crossover) that compared two or more pharmacological treatments or placebo in patients with secondary Raynaud's phenomenon. Individual patient data were obtained for one unpublished RCT. Three researchers independently screened the texts and extracted the data. Efficacy outcomes included severity (on a ten-point scale), daily frequency, and mean duration of Raynaud's phenomenon attacks. We also examined tolerability and acceptability. Pairwise meta-analyses and Bayesian random-effects network meta-analyses were used to synthesise data. This study is registered with PROSPERO (CRD42017057518).
FINDINGS RESULTS
We included 58 RCTs in the analysis, comprising 3867 patients (3540 [91·5%] with secondary Raynaud's phenomenon) and 15 classes of drugs. Phosphodiesterase 5 (PDE5) inhibitors were more effective than placebo for frequency (mean difference -0·36 [95% credibility interval -0·69 to -0·04]), severity (-0·34 [-0·66 to -0·03]), and duration (-3·42 [-6·62 to -0·29]) of attacks (low to moderate level of evidence). Calcium channel blockers (CCBs) were superior to placebo for frequency (-0·35 [-0·67 to -0·02]) and severity (-0·84 [-1·25 to -0·45]) of attacks (low level of evidence). For severity of attacks, selective serotonin-reuptake inhibitors (-1·54 [-2·68 to -0·41]; very low level of evidence) and oral prostacyclin receptor agonists (-0·48 [-0·80 to -0·16]; low level of evidence) were superior to placebo. No other drug classes were significantly superior to placebo with regard to efficacy outcomes. Compared with placebo, tolerability was lower for PDE5 inhibitors (incidence rate ratio for serious adverse events or early study exit due to adverse events 3·30 [95% CrI 1·49 to 7·55]) and CCBs (3·13 [1·33 to 7·04]). For all outcomes, global heterogeneity and between-study variance ranged from low (I
INTERPRETATION CONCLUSIONS
PDE5 inhibitors and CCBs are the most effective pharmacological options, albeit with moderate efficacy and a low level of evidence. Current evidence does not support the use of any other drug in secondary Raynaud's phenomenon.
FUNDING BACKGROUND
None.

Identifiants

DOI: 10.1016/S2665-9913(19)30079-7 PMID: 38229380
pubmed: 38229380
pii: S2665-9913(19)30079-7
doi: 10.1016/S2665-9913(19)30079-7
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e237-e246

Informations de copyright

Copyright © 2019 Elsevier Ltd. All rights reserved.

Auteurs

Charles Khouri (C)

Pharmacovigilance Unit, Grenoble Alpes University Hospital, Grenoble, France; Clinical Pharmacology Department, INSERM CIC1406, Grenoble Alpes University Hospital, Grenoble, France; HP2 Laboratory, U1042 INSERM, Grenoble Alpes University, Grenoble, France.

Marion Lepelley (M)

Pharmacovigilance Unit, Grenoble Alpes University Hospital, Grenoble, France.

Sebastien Bailly (S)

EFCR Laboratory, Grenoble Alpes University Hospital, Grenoble, France; HP2 Laboratory, U1042 INSERM, Grenoble Alpes University, Grenoble, France.

Sophie Blaise (S)

Department of Vascular Medicine, Grenoble Alpes University Hospital, Grenoble, France; HP2 Laboratory, U1042 INSERM, Grenoble Alpes University, Grenoble, France.

Ariane L Herrick (AL)

Centre for Musculoskeletal Research, University of Manchester, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.

Marco Matucci-Cerinic (M)

Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Department of Geriatric Medicine, Division of Rheumatology and Scleroderma Unit, Careggi University Hospital, Florence, Italy.

Yannick Allanore (Y)

INSERM U1016 UMR8104 Cochin Institute, Paris Descartes University, Paris, France; Rheumatology A Department, Cochin Hospital, Paris Descartes University, Paris, France.

Ludovic Trinquart (L)

Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.

Jean-Luc Cracowski (JL)

Clinical Pharmacology Department, INSERM CIC1406, Grenoble Alpes University Hospital, Grenoble, France; HP2 Laboratory, U1042 INSERM, Grenoble Alpes University, Grenoble, France.

Matthieu Roustit (M)

Clinical Pharmacology Department, INSERM CIC1406, Grenoble Alpes University Hospital, Grenoble, France; HP2 Laboratory, U1042 INSERM, Grenoble Alpes University, Grenoble, France. Electronic address: mroustit@chu-grenoble.fr.

Classifications MeSH