Independent association of glucocorticoids with damage accrual in SLE

Abstract

ObjectivesTo determine factors associated with damage accrual in a prospective cohort of patients with SLE.MethodsPatients with SLE who attended the Lupus Clinic at Monash Health, Australia, between 2007 and 2013 were studied. Clinical variables included disease activity (Systemic Lupus Erythematosus Disease Activity Index-2K, SLEDAI-2K), time-adjusted mean SLEDAI, cumulative glucocorticoid dose and organ damage (Systemic Lupus International Collaborating Clinics Damage Index (SDI)). Multivariate logistic regression analyses were performed to identify factors associated with damage accrual.ResultsA total of 162 patients were observed over a median (IQR) 3.6 (2.0–4.7) years. Seventy-five per cent (n=121) of patients received glucocorticoids. Damage accrual was significantly more frequent in glucocorticoid-exposed patients (42% vs 15%, p<0.01). Higher glucocorticoid exposure was independently associated with overall damage accrual after controlling for factors including ethnicity and disease activity and was significant at time-adjusted mean doses above 4.42 mg prednisolone/day; the OR of damage accrual in patients in the highest quartile of cumulative glucocorticoid exposure was over 10. Glucocorticoid exposure was independently associated with damage accrual in glucocorticoid-related and non-glucocorticoid related domains of the SDI.ConclusionsGlucocorticoid use is independently associated with the accrual of damage in SLE, including in non-glucocorticoid related domains.

Changing paradigms in the treatment of systemic lupus erythematosus

“…Nevertheless, management of patients with lupus still remains far from optimal, complete control of disease activity is only infrequently obtained,3–5 while patients considered to be in ‘remission’ by their treating physicians often report a considerable residual symptom burden 6. Persistent disease activity, together with flare-ups and accumulating toxicity from chronic use of glucocorticoids (GC) and immunosuppressive (IS) drugs, all contribute to the risk of progressive irreversible damage accrual, the latter ultimately associated with reduced survival 7 8…”

“…By using this practice, we rarely start prednisone at a dose higher than 0.5–0.6 mg/kg/day, which is followed by a rigorous effort to reduce to a safe maintenance dose within 4–6 months. Regarding the latter, although most reports have used 7.5 mg/day as a cut-off, above which the risk for damage accrual increases considerably,33 34 even lower daily doses (4.4–6 mg/day) have been associated with a significantly increased risk in individual studies 8 35. It would be prudent to recommend that treating physicians should aim at the lowest possible dose of prednisone, and by no means more than 7.5 g/day after 6 months.…”

10 most important contemporary challenges in the management of SLE

“…In a recent survey by the Systemic Lupus International Collaborating Clinics (SLICC) group, almost 33% of patients never discontinued GCs after a mean follow-up of 7.26 years 4. Several studies have emphasised the risk of damage accrual in a patient with SLE treated with GC, including at low doses such as 5 mg/day or 7.5 mg/day of prednisone-equivalent 5. The initial GC dose is a strong predictor of the overall GC exposure independent of initial disease activity, with potential overtreatment in those with limited disease activity 6.…”

Systemic lupus erythematosus: new horizons for diagnosis and therapy

“…Благодаря глобальному действию на патогенетические механизмы воспаления и нарушения иммунорегуляции ГК продолжают занимать центральное место в лечении СКВ, особенно при тяжелом течении заболевания [35,36]. Однако длительный пероральный прием ГК даже в низких дозах (≤7,5 мг/сут) приводит к накоплению необратимых органных повреждений [37] и развитию широкого спектра других нежелательных лекарственных реакций (НЛР) [32,38]. Примечательно, что в реальной клинической практике назначаемая врачом начальная доза ГК нередко не соответствует активности болезни и приводит к «перелечиванию» пациентов [39].…”