Study: Immunosuppressant Withdrawal Feasible, Safe for Many Patients With SLE and Lupus Nephritis

A minority of patients will experience flares, but in most cases reintroduction of therapy will result in remission.

Patients taking glucocorticoids and other immunosuppressants for systemic lupus erythematosus (SLE) or lupus nephritis can be successfully weaned from therapy, at least in cases where patients experience complete clinical remission following prolonged therapy, according to a new review article.

The report, published in the Clinical Journal of the American Society of Nephrology, is based on a series of existing studies in which investigators attempted to withdraw the therapy in patients. The authors noted that glucocorticoids and immunosuppressants generally remain the “cornerstone” of treatment for SLE and lupus nephritis. Yet, in recent years, the minimization or elimination of glucocorticoids has been generally recommended when possible to eliminate the potential for long-term complications from immunosuppressant therapy.

The authors noted that surveys suggest clinicians are reluctant to reduce therapy when patients have persistent serological abnormalities and previous organ involvement.

“On the other hand, even low doses of prednisone between 6 and 12 mg per day cause a higher risk of organ damage, and the long-term use of antiproliferative drugs such as mycophenolate and azathioprine may expose [patients] to disquieting side effects, such as opportunistic infections, bone marrow toxicity, and malignancy,” they wrote. Given the “unsatisfactory” nature of lupus nephritis management, the investigators sought to consult existing literature in hopes of finding clarity.

The authors said the initial conventional wisdom was that withdrawal of immunosuppressive agents in patients with lupus nephritis was ill advised, due to fears that it could lead to flares or irreversible kidney damage. However, more recent evidence has suggested that slow and progressive tapering of therapy can be done successfully.

For instance, the largest trial of immunosuppressive therapy interruption in patients with lupus nephritis found 10.6% of patients experienced flares during therapy reduction, but all but 1 patient (20 of 21) went into remission with treatment reinforcement. Half of those patients (10 of 20) were still without therapy after a median follow-up of 24 years.

In SLE, a recent study showed that among 77 patients who successfully stopped glucocorticoids, 23% reported experiencing flares after a median of 1 year compared with 69.8% of patients who continued taking glucocorticoids.

After reviewing other studies, the authors concluded that patients who had been relapse free for at least 4 years and are in complete remission are potential candidates for the complete discontinuation of immunosuppressant therapy.

“However, it may be burdened by flares of lupus activity in one-third to one-quarter of patients,” they said. “Flares occur, particularly in the period of drug-tapering and in the first years after therapy withdrawal. Thus, regular monitoring is mandatory.”

When such flares occur, the prompt reintroduction of glucocorticoids or other immunosuppressants can spark remission, they added.

When deciding if a patient is a good candidate for immunosuppression withdrawal, the authors suggested a number of factors. First, withdrawal tends to be more successful when patients have been on immunosuppressive therapy for a long time, at least 5 to 6 years. Second, patients should be in complete remission before considering withdrawal. Repeated kidney biopsy can be helpful in making a decision, but it is not necessary, they said.

The authors added that hydroxychloroquine can help prevent extrarenal flares. Finally, they said rapidly reinstating treatment in cases of flares can help offset damage.

Reference

Moroni G, Frontini G, Ponticelli C. When and how is it possible to stop therapy in patients with lupus nephritis? Clin J Am Soc Nephrol. Published online June 23, 2021. doi:10.2215/CJN.04830421