When and How Is It Possible to Stop Therapy in Patients with Lupus Nephritis

Abstract

Glucocorticoids and other immunosuppressants still represent the cornerstone drugs for the management of SLE (Systemic Lupus Erythematosus) and lupus nephritis. The refined use of these drugs over the years has allowed to obtain stable disease remission and improvement of the long-term kidney and patient survival. Nevertheless, a prolonged use of immunosuppressive agents may be accompanied by severe and even life-threatening side effects. Theoretically, a transient or even definitive withdrawal of immunosuppression could be useful to prevent iatrogenic morbidities. For many years, however, the risk of SLE reactivation has held clinicians back from trying to interrupt therapy. In this review we report the results of the attempts to interrupt glucocorticoids and other immunosuppressive agents in lupus nephritis and in SLE. The available data suggest that the therapy withdrawal is feasible at least in patients enjoying a complete clinical remission after a prolonged therapy. A slow and gradual reduction of treatment under medical surveillance is needed to prevent flares of activity. After therapy withdrawal around one quarter of patients may have kidney or systemic flares. However, most flares may respond to therapy if rapidly diagnosed. The other patients can enter stable remission even for 20 years or more. The use of antimalarials can help in maintaining the remission after the withdrawal of the immunosuppressive therapy. A repeated kidney biopsy could be of help in deciding to stop therapy, but given the few available data, it cannot be considered essential.

Weaning of maintenance immunosuppressive therapy in lupus nephritis (WIN-Lupus): results of a multicentre randomised controlled trial

“…Indeed, in a national survey,22 55% of physicians managing patients with LN reported continuing low-dose corticosteroids in maintenance. WIN-Lupus was not a trial of complete treatment withdrawal, as reported in recent cohort studies 4. One of the possible reasons for clinicians to maintain IST is to prevent the need for corticosteroid use or increase,34 which is itself associated with significant damage 35 36.…”

“…WIN-Lupus was not a trial of complete treatment withdrawal, as reported in recent cohort studies. 4 One of the possible reasons for clinicians to maintain IST is to prevent the need for corticosteroid use or increase, 34 which is itself associated with significant damage. 35 36 Here, the overall exposure to corticosteroids did not differ between the groups, indicating that IST discontinuation did not lead to a compensatory increase in corticosteroid dose for lupus containment.…”

“…Lupus nephritis (LN) is a frequent and severe manifestation of systemic lupus erythematosus (SLE) 1. Although the prognosis of LN has improved, substantial morbidity, partly related to treatment, is still observed 2–5. The therapeutic strategy relies on pathological classification of renal lesions 6 7.…”

“…Renal relapses nevertheless occur in 15‒43% of patients after 3 years,8–10 and 10%–20% of patients reach end-stage kidney disease (ESKD) after 10 years 9–11. The optimal duration of immunosuppressive therapy (IST) in proliferative LN is unknown and the possibility of discontinuing IST in patients in remission is still open to debate 3 4 12–14. While IST reduction or discontinuation before 18 months appears to be associated with a high risk of relapse,15 with subsequent organ damage, long-term continuation of IST could be associated with higher rates of adverse events such as cardiovascular events, infections and malignancy 2…”

Exosomes as Crucial Players in Pathogenesis of Systemic Lupus Erythematosus

“…Currently, SLE is treated with the application of biological agents, which provide relief and minimize the use of glucocorticoids [ 7 ]. SLE patients still require long-term drug-based maintenance, which often has toxic side effects [ 8 ]. Long-term use of glucocorticoids can even lead to emotional disorders such as depression in patients [ 9 ].…”