Health status and concomitant prescription of immunosuppressants are risk factors for hydroxychloroquine non-adherence in systemic lupus patients with prolonged inactive disease

Abstract

Background/objective

The objectives of this paper are to assess the extent of and the factors associated with hydroxychloroquine (HCQ) non-adherence in systemic lupus erythematosus (SLE) patients with prolonged inactive disease and to investigate relationships between blood HCQ concentration and quality of life (QoL).

Methods

Consecutive SLE patients, in remission for at least one year and taking a stable dose of HCQ were investigated. At study entry (T0) and six months later (T6) a blood venous sample was taken to measure whole blood concentration of [HCQ] and desethylchloroquine ([DCQ]). Moreover, at T0 each patient completed validated questionnaires assessing QoL, disability, anxiety, depression and visual analogue scales for fatigue, pain, general health (GH), and self-assessment of disease activity.

Results

Eighty-three patients with a median [HCQ] of 327 ng/ml were enrolled. At T0, 24 (29%) were defined as non-adherent ([HCQ] < 100 ng/ml). At multiple logistic regression analysis the physical summary of SF-36 (p = 0.038), and the concomitant use of immunosuppressants (p = 0.010) were independently associated with non-adherence. A significant increase of HCQ adherence was observed at T6 (p < 0.05).

Conclusions

A better health status and the concomitant prescription of immunosuppressants represent risk factors for HCQ non-adherence in SLE patients in remission. Monitoring HCQ levels might represent an important opportunity to improve adherence.

Keywords

Systemic lupus erythematosus hydroxychloroquine quality of life treatment adherence

Get full access to this article

View all access options for this article.

References

Agmon-Levin

Mosca

Petri

Shoenfeld

. Systemic lupus erythematosus one disease or many? Autoimmun Rev 2012; 11: 593–595.

Carter

Barr

Clarke

. The global burden of SLE: Prevalence, health disparities and socioeconomic impact. Nat Rev Rheumatol 2016; 12: 605–620.

Costedoat-Chalumeau

Dunogué

Morel

Le Guern

Guettrot-Imbert

. Hydroxychloroquine: A multifaceted treatment in lupus. Presse Med 2014; 43: e167–e180.

Costedoat-Chalumeau

Amoura

Hulot

et al.

Very low blood hydroxychloroquine concentration as an objective marker of poor adherence to treatment of systemic lupus erythematosus. Ann Rheum Dis 2007; 66: 821–824.

Costedoat-Chalumeau

Amoura

Hulot

et al.

Low blood concentration of hydroxychloroquine is a marker for and predictor of disease exacerbations in patients with systemic lupus erythematosus. Arthritis Rheum 2006; 54: 3284–3290.

Schmeding

Schneider

. Fatigue, health-related quality of life and other patient-reported outcomes in systemic lupus erythematosus. Best Pract Res Clin Rheumatol 2013; 27: 363–375.

Rohleder

Aringer

Boentert

. Role of interleukin-6 in stress, sleep, and fatigue. Ann N Y Acad Sci 2012; 1261: 88–96.

Petri

Orbai

Alarcón

et al.

Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 2012; 64: 2677–2686.

Wilhelm

Magder

Petri

. Remission in systemic lupus erythematosus: Durable remission is rare. Ann Rheum Dis 2017; 76: 547–553.

10.

Buyon

Petri

Kim

et al.

The effect of combined estrogen and progesterone hormone replacement therapy on disease activity in systemic lupus erythematosus: A randomized trial. Ann Intern Med 2005; 142: 953–962.

11.

Gladman

Ginzler

Goldsmith

et al.

The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum 1996; 39: 363–369.

12.

Levey

Stevens

Schmid

et al.

A new equation to estimate glomerular filtration rate. Ann Intern Med 2009; 150: 604–612.

13.

Wolfe

Clauw

Fitzcharles

et al.

The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res 2010; 62: 600–610.

14.

Apolone

Mosconi

. The Italian SF-36 Health Survey: Translation, validation and norming. J Clin Epidemiol 1998; 51: 1025–1036.

15.

Ranza

Marchesoni

Calori

et al.

The Italian version of the Functional Disability Index of the Health Assessment Questionnaire. A reliable instrument for multicenter studies on rheumatoid arthritis. Clin Exp Rheumatol 1993; 11: 123–128.

16.

Costantini

Musso

Viterbori

et al.

Detecting psychological distress in cancer patients: Validity of the Italian version of the Hospital Anxiety and Depression Scale. Support Care Cancer 1999; 7: 121–127.

17.

Snaith

. The Hospital Anxiety and Depression Scale. Health Qual Life Outcomes 2003; 1: 29–29.

18.

van Vollenhoven

Mosca

Bertsias

et al.

Treat-to-target in systemic lupus erythematosus: Recommendations from an international task force. Ann Rheum Dis 2014; 73: 958–967.

19.

Petri

Kim

Kalunian

et al.

Combined oral contraceptives in women with systemic lupus erythematosus. N Engl J Med 2005; 353: 2550–2558.

20.

Costedoat-Chalumeau

Galicier

Aumaître

et al.

Hydroxychloroquine in systemic lupus erythematosus: Results of a French multicentre controlled trial (PLUS Study). Ann Rheum Dis 2013; 72: 1786–1792.

21.

Costedoat-Chalumeau

Houssiau

Izmirly

et al.

Adherence to hydroxychloroquine as assessed by measurements of drug and metabolite blood levels in an international prospective study of SLE patients in flare. Ann Rheum Dis 2016; 75: 297–297.

22.

Halpern

Becker

Iqbal

Kazis

Macarios

Badamgarav

. The association of adherence to osteoporosis therapies with fracture, all-cause medical costs, and all-cause hospitalizations: A retrospective claims analysis of female health plan enrollees with osteoporosis. J Manag Care Pharm 2011; 17: 25–39.

23.

Hugtenburg

Timmers

Elders

Vervloet

van Dijk

. Definitions, variants, and causes of nonadherence with medication: A challenge for tailored interventions. Patient Prefer Adherence 2013; 7: 675–682.

24.

Ting

Kudalkar

Nelson

et al.

Usefulness of cellular text messaging for improving adherence among adolescents and young adults with systemic lupus erythematosus. J Rheumatol 2012; 39: 174–179.

25.

Marmor

Kellner

Lai

Melles

Mieler

. American Academy of Ophthalmology. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology 2016; 123: 1386–1394.

26.

Jolly

Galicier

Aumaître

et al.

Quality of life in systemic lupus erythematosus: Description in a cohort of French patients and association with blood hydroxychloroquine levels. Lupus 2016; 25: 735–740.

27.

Kuriya

Gladman

Ibañez

Urowitz

. Quality of life over time in patients with systemic lupus erythematosus. Arthritis Rheum 2008; 59: 181–185.

28.

Durcan

Clarke

Magder

Petri

. Hydroxychloroquine blood levels in systemic lupus erythematosus: Clarifying dosing controversies and improving adherence. J Rheumatol 2015; 42: 2092–2097.

29.

Jallouli

Galicier

Zahr

et al.

Determinants of hydroxychloroquine blood concentration variations in systemic lupus erythematosus. Arthritis Rheumatol 2015; 67: 2176–2184.