title: Hydroxychloroquine Serum Concentrations and Flares of Systemic Lupus Erythematosus: A Longitudinal Cohort Analysis.
abstract: To study the relationship between serum hydroxychloroquine (HCQ) concentrations and flares of systemic lupus erythematosus (SLE) in a longitudinal cohort of patients.
  
  
  
  Patients who fulfilled ≥4 American College of Rheumatology classification criteria for SLE and had been treated with HCQ for >6 months were studied. Blood was assayed for HCQ levels by tandem mass spectrometry. Patients were serially assessed for disease activity, using the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and flares (SELENA flares instrument). Comparison of the mean summated SLEDAI scores over time and rates of flares in groups with different HCQ levels was performed by the Kruskal-Wallis test.
  
  
  
  A total of 276 SLE patients were studied (93% women, mean ± SD age 41.0 ± 13.8 years). The proportion of patients with HCQ levels <10 (total noncompliance), 10-500 (subtherapeutic), and >500 ng/ml (therapeutic) was 11%, 77%, and 12%, respectively. HCQ levels correlated significantly with the prescribed dose but not with body weight or renal function. The prescribed HCQ dose also correlated significantly with baseline SLEDAI scores, indicating that higher doses were used for more active manifestations. After a mean ± SD observation period of 32.5 ± 5.5 months, the mean summated SLEDAI score and the incidence of SLE flares was not statistically different among patients with different baseline HCQ levels. In a subgroup of 73 patients with serologic and clinical remission and having therapeutic HCQ levels, a trend of lower disease activity and fewer incidences of flares was observed.
  
  
  
  Noncompliance and subtherapeutic serum HCQ levels were seen frequently in these SLE patients, which was partly due to the low prescribed dose. In patients in remission, higher HCQ concentrations were associated with a trend showing fewer flares over time.
authors.affiliation: Tuen Mun Hospital, Hong Kong, China.
authors.forename: Chi Chiu
authors.initials: CC
authors.lastname: Mok
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Hannah J
authors.initials: HJ
authors.lastname: Penn
authors.affiliation: Tuen Mun Hospital, Hong Kong, China.
authors.forename: Kar Li
authors.initials: KL
authors.lastname: Chan
authors.affiliation: Tuen Mun Hospital, Hong Kong, China.
authors.forename: Sau Mei
authors.initials: SM
authors.lastname: Tse
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Loralie J
authors.initials: LJ
authors.lastname: Langman
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Jannetto
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000097:blood* / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000097:blood* / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D053719:Tandem Mass Spectrometry
chemical_list: D018501:Antirheumatic Agents; D006886:Hydroxychloroquine