Hydroxychloroquine in systemic lupus erythematosus: results of a French multicentre controlled trial (PLUS Study).
Nathalie Costedoat-Chalumeau
(1)
,
Lionel Galicier
(2)
,
Olivier Aumaître
(3)
,
Camille Francès
(4)
,
Véronique Le Guern
(5, 6)
,
Frédéric Lioté
(7)
,
Amar Smail
,
Nicolas Limal
,
Laurent Perard
,
Hélène Desmurs-Clavel
,
Du Le Thi Huong Boutin
,
Bouchra Asli
,
Jean-Emmanuel Kahn
(8)
,
Jacques Pourrat
(9)
,
Laurent Sailler
,
Félix Ackermann
,
Thomas Papo
(10)
,
Karim Sacré
,
Olivier Fain
(11)
,
Jerome Stirnemann
(12)
,
Patrice Cacoub
(13, 14)
,
Moez Jallouli
,
Gaelle Leroux
(15)
,
Judith Cohen-Bittan
,
Marie-Laure Tanguy
(13)
,
Jean-Sébastien Hulot
(16)
,
Philippe Lechat
,
Lucile Musset
(13)
,
Zahir Amoura
(13, 17)
,
Jean-Charles Piette
(13)
,
Aurelien Delluc
(18, 19, 20)
1
I3 -
Immunologie - Immunopathologie - Immunothérapeutique
2 Service d'immunologie clinique
3 Service de Médecine Interne [CHU Clermont-Ferrand]
4 CHU Tenon [AP-HP]
5 CHU Saint-Antoine [AP-HP]
6 Service de Médecine Interne
7 Service Rhumatologie
8 EA 2686 - Laboratoire d'Immunologie
9 Service de Néphrologie - Immunologie Clinique [Toulouse]
10 Hôpital Bichat - Claude Bernard
11 Service de médecine interne
12 U738 / UMR_S738 - Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques
13 CHU Pitié-Salpêtrière [AP-HP]
14 BTPI - Biologie et thérapeutique des pathologies immunitaires
15 IMN - Institut des Maladies Neurodégénératives [Bordeaux]
16 Physiopathologie, génétique et pharmacologie du remodelage cardiovasculaire
17 Immunité et Infection
18 DMIP - Brest - Département de Médecine Interne et Pneumologie [Brest]
19 GETBO - Groupe d'Etude de la Thrombose de Bretagne Occidentale
20 CIC - Brest - Centre d'Investigation Clinique
2 Service d'immunologie clinique
3 Service de Médecine Interne [CHU Clermont-Ferrand]
4 CHU Tenon [AP-HP]
5 CHU Saint-Antoine [AP-HP]
6 Service de Médecine Interne
7 Service Rhumatologie
8 EA 2686 - Laboratoire d'Immunologie
9 Service de Néphrologie - Immunologie Clinique [Toulouse]
10 Hôpital Bichat - Claude Bernard
11 Service de médecine interne
12 U738 / UMR_S738 - Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques
13 CHU Pitié-Salpêtrière [AP-HP]
14 BTPI - Biologie et thérapeutique des pathologies immunitaires
15 IMN - Institut des Maladies Neurodégénératives [Bordeaux]
16 Physiopathologie, génétique et pharmacologie du remodelage cardiovasculaire
17 Immunité et Infection
18 DMIP - Brest - Département de Médecine Interne et Pneumologie [Brest]
19 GETBO - Groupe d'Etude de la Thrombose de Bretagne Occidentale
20 CIC - Brest - Centre d'Investigation Clinique
Nathalie Costedoat-Chalumeau
- Function : Author
- PersonId : 768024
- ORCID : 0000-0002-1555-9021
Lionel Galicier
- Function : Author
- PersonId : 762207
- ORCID : 0000-0002-0360-7620
Amar Smail
- Function : Author
Nicolas Limal
- Function : Author
Laurent Perard
- Function : Author
Hélène Desmurs-Clavel
- Function : Author
Du Le Thi Huong Boutin
- Function : Author
Bouchra Asli
- Function : Author
Laurent Sailler
- Function : Author
Félix Ackermann
- Function : Author
Karim Sacré
- Function : Author
Patrice Cacoub
- Function : Author
- PersonId : 759698
- ORCID : 0000-0002-6727-4992
- IdRef : 035642769
Moez Jallouli
- Function : Author
Judith Cohen-Bittan
- Function : Author
Jean-Sébastien Hulot
- Function : Author
- PersonId : 759557
- ORCID : 0000-0001-5463-6117
- IdRef : 058500391
Philippe Lechat
- Function : Author
Aurelien Delluc
- Function : Author
- PersonId : 924054
Abstract
INTRODUCTION: Hydroxychloroquine (HCQ) is an important medication for treating systemic lupus erythematosus (SLE). Its blood concentration ([HCQ]) varies widely between patients and is a marker and predictor of SLE flares. This prospective randomised, double-blind, placebo-controlled, multicentre study sought to compare standard and adjusted HCQ dosing schedules that target [HCQ] ≥1000 ng/ml to reduce SLE flares. PATIENTS AND METHODS: [HCQ] was measured in 573 patients with SLE (stable disease and SELENA-SLEDAI≤12) treated with HCQ for at least 6 months. Patients with [HCQ] from 100 to 750 ng/ml were randomised to one of two treatment groups: no daily dose change (group 1) or increased HCQ dose to achieve the target [HCQ] (group 2). The primary end point was the number of patients with flares during 7 months of follow-up. RESULTS: Overall, mean [HCQ] was 918±451 ng/ml. Active SLE was less prevalent in patients with higher [HCQ]. A total of 171 patients were randomised and followed for 7 months. SLE flare rates were similar in the two groups (25% in group 1 vs 27.6% in group 2; p=0.7), but a significant spontaneous increase in [HCQ] in both groups between inclusion and randomisation strongly suggested improved treatment adherence. Patients at the therapeutic target throughout follow-up tended to have fewer flares than those with low [HCQ] (20.5% vs 35.1%, p=0.12). CONCLUSIONS: Although low [HCQ] is associated with higher SLE activity, adapting the HCQ dose did not reduce SLE flares over a 7-month follow-up.