Clinical trial NCT01509989: International Prospective Study on Adherence to Treatment in Patients With Active Systemic Lupus Erythematosus
Official title: International Prospective Study on Adherence to Treatment in Patients With Active Systemic Lupus Erythematosus
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Systemic Lupus Erythematosus
Keywords: Adherence
Compliance
Systemic Lupus Erythematosus
Hydroxychloroquine
Blood monitoring
Flares
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2012-01-13
Enrollment: 307
Sex: ALL
Minimum age (years): 6
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Active Systemic Lupus Erythematosus (see eligibility criteria)

Brief summary: The treatment of systemic lupus erythematosus (SLE) may change in the future due to the availability of new biological treatments, especially monoclonal antibodies in patients with active disease. However, one of the main causes of treatment failure in SLE is the lack of treatment adherence since "drugs don't work in patients who don't take them." Hydroxychloroquine (HCQ-Plaquenil) has a long terminal elimination half- life, and investigators have demonstrated that patients who do not take HCQ for a long time have undetectable or very-low blood HCQ concentrations (\< 200 ng/ml). The rate of severe non-adherence was 7% in a cohort of 203 patients and was even higher in patients with active disease: 8 out of 35 (23%) in patients with a SLEDAI ≥6 and 6 out of 20 (30%) in patients with a SLEDAI ≥12.

Investigators will evaluate the importance of non-adherence to the treatment in a large population of SLE patients with active disease. This will be done with blood HCQ monitoring in a translational multicentric prospective study.

Detailed description: This international multicentric prospective study is an observational study that will include consecutive SLE patients treated with HCQ and with SLE flare (defined by the SELENA-SLEDAI flare composite). The study will only require the sampling of 1 vial of whole blood for the dosage of HCQ (that would be centralized and performed in PITIE-SALPETRIERE Hospital at the completion of the study). The patients and the physicians will also have adherence self-questionnaires to complete, and the physicians will complete a patient data sheet.

The end points are adherence of the treatment in the whole group, and subgroups, adherence according to the severity of SLE, and the relationship between patient's questionnaires, physician evaluation of adherence and blood HCQ dosage.

If investigators confirm their previous data, this study might demonstrate that a significant proportion of patient candidates for treatment escalation are in fact nonadherent to the treatment. It might further demonstrate the interest of HCQ concentrations monitoring, both in "real life" and in therapeutic study in SLE as it may avoid unnecessary, expensive or even hazardous regimen escalation.

Eligibility criteria: Inclusion criteria :

* History of meeting 4 American College of Rheumatology (ACR) criteria for systemic lupus erythematosus including a positive test for antinuclear antibodies,
* SLE flare defined by the SELENA-SLEDAI flare composite
* Treatment with HCQ for at least 2 months with a daily dosage \> or equal to 200 mg/day.

Exclusion criteria :

* Patients who are not able to take their medications (notably patients with repeated vomiting and patients who are not allowed to take oral medications)

Primary outcomes:
measure: Adherence to the treatment in the whole group.
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 1
Secondary outcomes:
measure: Secondary outcome
timeFrame: up to 3 weeks
Other outcomes:
Locations:
city: Paris
country: France
facility: Hopital Cochin
Study officials:
affiliation: Service de Médecine Interne, Hopital Cochin, 27, rue du Faubourg St Jacques, 75014 Paris, France. Email : nathalie.costedoat@gmail.com
name: Nathalie Costedoat-Chalumeau, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dept of Rheumatology, 1830 Building, Suite 7500. Email: mpetri@jhmi.edu
name: Michelle Petri, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: 560 First avenue, TCH-407, New York-NY 10016. Email: jill.buyon@nyumc.org
name: Jill Buyon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lupus Clinic, Montreal General Hospital, Room A6163, 1650 Cedar Ave, Montreal, Quebec, Canada, H3G 1A4. Email: ann.clarke@mcgill.ca
name: Ann Clarke, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rheumatology Unit, Internal Medicine Department, Cliniques universitaires Saint-Luc, Université catholique de Louvain,Bruxelles, Belgium. Email: Frederic.Houssiau@uclouvain.be
name: Frederic Houssiau, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Autoimmune Disease Research Unit, Internal Medicine Department,Hospital de Cruces, University of the Basque Country, Barakaldo, Spain. Email: r.irastorza@euskaltel.net
name: Guillermo Ruiz-Irastorza, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Autoimmune Diseases, Hospital Clínic, rcervera@clinic.ub.es Barcelona, Catalonia, Spain. Email: rcervera@clinic.ub.es
name: Ricard Cervera, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department Inflammation, UCL Division of Medicine, Room 331 The Windeyer Building, 46 Cleveland Street, London, England. Email: d.isenberg@ucl.ac.uk
name: David Isenberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 52621, Israel. Email: shoenfel@post.tau.ac.il
name: Yehuda Shoenfeld, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Unit for Clinical Therapy Research, Inflammatory Diseases (ClinTRID), The Karolinska University Hospital, D10:0, Department of Rheumatology, 17176 Stockholm, Sweden. Email: Ronald.van.Vollenhoven@ki.se
name: Ronald F. van Vollenhoven, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Service de Médecine Interne, Hôpital Claude Huriez, 1, place Verdun, 59000 Lille. Email: ehachulla2@yahoo.fr
name: Eric Hachulla, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Service de Médecine Interne, Hôpital Haut Lévêque, Centre François Magendie, 1, avenue Magellan, 33604 Pessac Cedex. Email: jean-francois.viallard@chu-bordeaux.fr
name: Jean-François Viallard, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Service de Médecine Interne, Hôpital Cochin, 27, rue du Faubourg Saint-Jacques, 75679 PARIS Cedex 14. Email: loic.guillevin@wanadoo.fr
name: Loïc Guillevin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Service de Médecine Interne, Hôpital Cochin, 27, rue du Faubourg Saint-Jacques, 75679 PARIS Cedex 14. Email: luc.mouthon@cch.aphp.fr
name: Luc Mouthon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Service de Médecine Interne, Hôpital Cochin, 27, rue du Faubourg Saint-Jacques, 75679 PARIS Cedex 14.
name: Veronique Leguern, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Service de Médecine Interne, Hopital Pitié-Salpêtrière, 47-83 Boulevard de l'hôpital, 75013 Paris, France. Email: jcpiette@free.fr
name: Jean-Charles Piette, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Service Immuno Clinique
name: Lionel Galicier, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Service de Médecine interne, Hôpital Dupuytren, 2, avenue Martin Luther King 87042 Limoges cedex
name: Anne Laure Fauchais, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Service de Médecine interne, Hôpital Dupuytren, 2, avenue Martin Luther King 87042 Limoges cedex
name: Holy Harifidy Bezanahrv, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Service de Médecine interne (3C), CHU de Martinique, Hôpital Pierre-Zobda-Quitman, CS 90631-97261 Fort de France cedex
name: Christophe deligny, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Santo Tomas Hospital, España Boulevard, Sampaloc, Manila, Philippines
name: Sandra Navarra, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Costedoat-Chalumeau N, Houssiau F, Izmirly P, Guern VL, Navarra S, Jolly M, Ruiz-Irastorza G, Baron G, Hachulla E, Agmon-Levin N, Shoenfeld Y, Dall'Ara F, Buyon J, Deligny C, Cervera R, Lazaro E, Bezanahary H, Leroux G, Morel N, Viallard JF, Pineau C, Galicier L, Vollenhoven RV, Tincani A, Nguyen H, Gondran G, Zahr N, Pouchot J, Piette JC, Petri M, Isenberg D. A Prospective International Study on Adherence to Treatment in 305 Patients With Flaring SLE: Assessment by Drug Levels and Self-Administered Questionnaires. Clin Pharmacol Ther. 2019 Aug;106(2):374-382. doi: 10.1002/cpt.1194. Epub 2018 Sep 2.
citation: Costedoat-Chalumeau N, Houssiau F, Izmirly P, Le Guern V, Navarra S, Jolly M, Ruiz-Irastorza G, Baron G, Hachulla E, Agmon-Levin N, Shoenfeld Y, Dall'Ara F, Buyon J, Deligny C, Cervera R, Lazaro E, Bezanahary H, Leroux G, Morel N, Viallard JF, Pineau C, Galicier L, Van Vollenhoven R, Tincani A, Nguyen H, Gondran G, Zahr N, Pouchot J, Piette JC, Petri M, Isenberg D. A Prospective International Study on Adherence to Treatment in 305 Patients With Flaring SLE: Assessment by Drug Levels and Self-Administered Questionnaires. Clin Pharmacol Ther. 2018 Jun;103(6):1074-1082. doi: 10.1002/cpt.885. Epub 2017 Nov 9.