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We thank Mousavi et al for their interest in our study.1 2 Mousavi et al regret that we did not take into account different factors determined in the literature to be associated with increased risk of flare of the disease, such as ‘African American ethnicity’, disease onset ≤25 years and B Lymphocyte Stimulator (BLyS) serum levels ≥2 ng/mL.3 However, the studies cited by Mousavi et al included active patients with systemic lupus erythematosus (SLE) (eg, with a Safety of Estrogens in Lupus Erythematosus National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score ≥6 for the Study of Belimumab in Subjects With Systemic Lupus Erythematosus (BLISS)-52 and BLISS-76 trials4), while in the CORTICOLUP study only clinically quiescent patients were included. The predictors of relapse are certainly not the same as for active or clinically quiescent patients. Predictors of flares in clinically quiescent patients are poorly known. They include age, disease duration, remission duration, high anti-dsDNA and hypocomplementaemia.5–7 These factors were assessed in the interaction analysis of the CORTICOLUP study. To answer more specifically to the comment of Mousavi et al, demographic classifications such as ‘African-American, Caucasians or Hispanics’, although requested by some health authorities, are non-relevant in France and other parts of the word. The French population of patients with SLE is widely multiethnic and includes a significant proportion of patients from African and Asian origin who were all represented in the CORTICOLUP. Morever, we think that these considerations do not affect the conclusions of the study because, as a result of the randomisation procedure, the frequencies of the different risk factors of flare mentioned by Mousavi et al should not differ between both groups. In this regard, the rate of patients with a disease onset ≤25 years was comparable in the group of patients who were withdrawn (38%) to those who were not (36%, p=0.9 using the χ2 test).
We, of course, do acknowledge that the results of the CORTICOLUP should be interpreted in light of its open-label design without a placebo group. However, we are not aware of studies showing that emotional stress due to treatment discontinuation is a recognised factor associated with an increased risk of lupus flare. We agree with Mousavi et al that we cannot be sure that all patients were actually taking their treatment regimen during the study. However, this limitation is frequent in clinical trials because, apart from a blood assessment of the drugs, it is difficult to be certain of the patients’ adherence to treatment.
Yet, the measurement of hydroxychloroquine (HCQ) blood levels is encouraging in this respect. We have reported that very low blood HCQ concentrations can serve as an objective marker for poor adherence to treatment for SLE.8 Using this assay, and as part of the overall assessment of the CORTICOLUP study, we have performed a post-hoc analysis, whose results do address the concern of Mousavi et al. For the patients treated with HCQ, only one patient in the group who were withdrawn from prednisone, and none of the patients in the group who continued prednisone intake, had HCQ blood levels<100 ng/mL at 3, 6, 9 and 12 months of the study. This result confirms the adherence of the patients in the CORTICOLUP study to the treatment.
To conclude, we agree with Mousavi et al that the goal of treatment maintenance is not just to prevent the disease flares. However, the reduction in the number of flares is certainly important because a consistent link between the number of flares and organ damage accrual, as well as the quality of life, healthcare cost and work productivity has previously been reported in the literature.3
Patient consent for publication
Handling editor Josef S Smolen
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Commissioned; internally peer reviewed.