Balancing risks and benefits in the use of hydroxychloroquine and glucocorticoids in systemic lupus erythematosus

ABSTRACT

Introduction

Hydroxychloroquine (HCQ) and glucocorticoids (GCs) constitute the oldest and more used drugs in the treatment of systemic lupus erythematosus (SLE). Despite this long experience, both are still subject to a number of uncertainties, mainly regarding the dose.

Areas covered

We review the main mechanisms of action, the clinical and toxic effects of HCQ and GCs and analyze the recommendations for the use of both in guidelines published since 2018. We offer a set of recommendations based on the pharmacology, mechanisms of action and clinical evidence.

Expert opinion

HCQ is the backbone therapy for SLE, and a judicious use must be accomplished, using doses that allow a good control of lupus without compromising the safety of treatments very much prolonged over the time. Stable doses of 200 mg/day seem to accomplish both conditions. GCs should be used more judiciously, with methyl-prednisolone pulses as the main therapy for inducing rapid remission and doses ≤5–2.5 mg/day be never exceeded in long-term maintenance treatments.

KEYWORDS:

• Glucocorticoids
• methylprednisolone
• prednisone
• lupus activity
• toxicity
• antimalarials
• hydroxychloroquine
• mepacrine

Article highlights

• Hydroxychloroquine (HCQ) and glucocorticoids (GCs) remain the cornerstone of systemic lupus erythematosus (SLE) therapy after more than 70 years of use.

• Long-term HCQ increases survival and reduces damage in lupus patients.

• HCQ doses of ≤5 mg/kg/day are effective and safe in the long-term for most lupus patients.

• Background treatment with HCQ is mandatory in every lupus patient unless severe (mainly retinal) toxicity is confirmed.

• Mepacrine represents an alternative to HCQ in cases of maculopathy and has a synergistic effect when added to HCQ in patients with skin, articular and/or serosal disease unresponsive to therapy.

• GCs are associated with dose- and time-dependent side-effects and damage accrual.

• We aim for adjusting the initial dose of GCs according to the severity of flares; the suggested starting doses for mild, moderate and severe flares are up to 7.5 mg/day, up to 10-15 mg/day and up to 20–30 mg/day, respectively.

• In any case, a rapid tapering of prednisone to doses of ≤5 mg/day, preferably ≤2.5 mg/d, would avoid GCs major side effects without reducing their efficacy as maintenance therapy.

• The use of methyl-prednisolone pulses and the early introduction of immunosuppressive drugs in moderate to severe flares allow a rapid control of activity and spare oral GCs.

• Oral GCs withdrawal could be attempted in patients in long-term stable remission on low doses, with the aim of the eventual discontinuation.

• Tapering to discontinuation should be done slowly.

Acknowledgments

We acknowledge ADELES Gipuzkoa and Asociación de Lupus y Autoinmunes de Castilla-La Mancha for their support.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

Dr Ruiz-Irastorza is supported by the Department of Education of the Basque Government, research grant [IT 1512-22].