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Link between severe non-adherence to hydroxychloroquine and SLE flares: SLICC cohort study

Jan 11, 2024
Learning objective: After reading this article, learners will be able to cite a new clinical development in systemic lupus erythematosus.

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The effectiveness of hydroxychloroquine (HCQ) is known to decrease with non-adherence (reported range, 3–85%) in patients with systemic lupus erythematosus (SLE). Here, we summarize the Systemic Lupus International Collaborating Clinics inception cohort study examining the association between severe non-adherence to HCQ and SLE flares, published by Nguyen et al.1 in Arthritis and Rheumatology.


In this international multicenter cohort study, serum of 660 patients receiving HCQ for at least 3 months was analyzed.

  • Serum HCQ levels of <53 ng/mL or <106 ng/mL for HCQ doses of 200 mg or 400 mg/day, respectively, were defined as severe non-adherence.
  • SLE flare was defined as an increase of ≥4 points in SLE Disease Activity Index 2000, use of prednisone or immunosuppressive drugs, or new renal involvement in the first year after time zero (T0).
  • SLE damage was defined as an increase of ≥1 point in Systemic Lupus International Collaborating Clinics Damage Index.

Key findings1

  • Overall, 7.3% of the patients included were severely non-adherent to HCQ.
    • HCQ levels of <53 ng/mL and <106 ng/mL were seen in 7.7% and 7.1% of patients receiving HCQ doses of 200 mg and 400 mg/day, respectively.
  • The median serum HCQ was 388 ng/mL (interquartile range [IQR], 244–566 ng/mL).
    • The median HCQ levels were 250 ng/mL (IQR, 158–365 ng/mL) and 427 ng/mL (IQR, 287–602 ng/mL) for HCQ doses of 200 and 400 mg/day, respectively.
  • In the univariate analysis:
    • Severe HCQ non-adherence (odds ratio [OR], 3.86), age (OR, 0.98), SLE Disease Activity Index 2000 (OR, 1.06), and treatment with azathioprine at T0 (OR, 1.95) were associated with an increased risk of SLE flares.
    • Black race (OR, 1.59), education (OR, 2.02), smoking (OR, 1.52), body mass index (OR, 1.03), treatment with azathioprine at T0 (OR, 2.01), and non-quantifiable serum HCQ level (OR, 1.99) were associated with an increased risk of SLE damage.
    • Severe HCQ non-adherence (hazard ratio, 5.41) was associated with a risk of death during the 5 years after T0.
  • Figure 1 shows the multivariate analysis of factors associated with SLE flare and damage.

Figure 1. Multivariate analysis of factors associated with SLE flare and damage* 

aHR, adjusted hazard ratio; aOR, adjusted odd ratio; CI, confidence interval; HCQ, hydroxychloroquine; SLE, systemic lupus erythematosus; SLEDAI-2K, SLE Disease Activity Index 2000 index; T0, time zero.
*Data from Nguyen, et al.1

Key learnings

  • The study demonstrated that severe HCQ non-adherence was associated with poor outcomes, such as SLE flares, damage, and mortality.
  • The findings highlight the need for systematic testing in patients with SLE to identify severe non-adherence.
    • Focusing resources on such patients to increase adherence may improve their long-term prognosis.

Question for expert

Expert opinion

This study demonstrates that non-compliance, measured by severe HCQ non-adherence, is associated with poor outcomes. This should prompt clinicians to better understand the causes of non-adherence and develop approaches to address them. In a previous study,2 we have demonstrated that non-compliance in at least 50% of patients is due to: concerns about harmful side effects, being easily distracted, life getting in the way, being unsure or disagreeing that their condition will worsen without medications, and personal reasons. Each of these patient concerns can be addressed through remedial approaches by physicians and other healthcare professionals treating patients with lupus.

  1. Nguyen Y, Blanchet B, Urowitz MB, et al. Association between severe nonadherence to hydroxychloroquine and systemic lupus erythematosus flares, damage, and mortality in 660 patients from the SLICC inception cohort. Arthritis Rheumatol. 2023;75(12):2195-2206. DOI: 10.1002/art.42645
  2. Hardy C, Gladman DD, Su J, et al. Barriers to medication adherence and degree of nonadherence in a systemic lupus erythematosus (SLE) outpatient population. Rheumatol Int. 2021;41(8):1457-1464. DOI: 10.1007/s00296-021-04898-0


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