Hydroxychloroquine blood levels in patients with systemic lupus erythematosus: Correlation with disease activity and end organ damage

Abstract

Systemic lupus erythematosus is an autoimmune disease characterized by immune complex depositions that cause inflammation and tissue damage in multiple organs. The clinical course of SLE is characterized by periods of both exacerbation and remission, with manifestations ranging from mild dermatological and joint symptoms to life threatening internal organ failures. The diagnosis is based on clinical and laboratory findings. The pharmacological management of patients with SLE revolves around four main classes of drugs, often in combination; non-steroidal anti inflammatory drugs (NSAIDs), anti-malarials, corticosteroids and cytotoxic drugs. Hydroxychloroquine has become a cornerstone in SLE treatment, acting on a range of different pathways and having many beneficial effects, such as immunomodulatory, anti-inflammatory, antiproliferative, and photoprotective effects. In addition to its efficacy in preventing SLE flares, HCQ protects against diabetes mellitus, thrombotic events, dyslipidaemia and overall damage accrual in patients with SLE. Our study included a convenient sample of 70 systemic lupus erythematosus patients, satisfying at least four of the revised American college of rheumatology (ACR) criteria for SLE, recruited from the outpatient clinic and inpatients at the department of internal medicine-Rheumatology division in Ain Shams university hospital. Patients who received pulse steroids or pulse cyclophosphamide therapy within one month were excluded from the study. We measured blood levels of HCQ and assessed the adherence of the studied patients to HCQ treatment and its relation to disease activity and end organ damage. It was found that half of the included patients had therapeutic HCQ blood level, while 44.29% had subtherapeutic HCQ blood level, and 5.71% had supratherapeutic HCQ blood level. Most of the patients 92.86% used HCQ for more than 6 months, while only 7.14 % used it for less than 6 months. Regarding daily dosage, 87.14% were prescribed 400mg HCQ, while only 12.86% were prescribed lower dose of 200mg. Compliant patients were 51.4% and non compliant patients were 48.6%. A significant relation between SLE disease activity and HCQ blood level was proven, as all of the patients with subtherapeutic HCQ blood level had active disease (P value <0.001). Comparison between patients with therapeutic and subtherapeutic HCQ blood level, showed that there is significant relation between HCQ blood level and SLICC damage index (P value <0.001). Additionally, significant negative correlations were found between duration of HCQ intake and SLEDAI index (P value <0.038). Patients with therapeutic HCQ blood level were found to be on HCQ treatment for longer duration, while there was no significant relation between daily dosage of HCQ and blood level of HCQ. Compliance to treatment with HCQ showed significant negative correlations with SLICC and SLEDAI indices (P value <0.001), and positive correlation with HCQ blood level; eighty three percent of the compliant patients had therapeutic HCQ blood level and eighty two percent of the non compliant patients had subtherapeutic HCQ blood levels. In conclusion: Patients with higher Hydroxychloroquine blood levels had less SLE disease activity and damage (lower SLEDAI and SLICC). Hydroxychloroquine blood levels are significantly affected by compliance and duration of intake. So, routine assay of HCQ blood concentration might help to optimize treatment efficacy, control disease activity, lessen disease damage, and most importantly detect non compliance.