Combination strategies for lupus nephritis: facts and controversies

ABSTRACT

Introduction

There is an unmet need to improve the efficacy of therapeutic regimens in lupus nephritis (LN). Cocktail immunosuppressive therapy for the synergistic effect of individual drugs may enhance efficacy and enable dosage reduction. However, the potential increase in the risk of serious and opportunistic infections is a concern. Moreover, the timing of combination therapy, adoption of a step-up or step-down approach, and the choice of drugs is still controversial, partly related to the cost-effectiveness issue.

Areas covered

Evidence of a combination of conventional, newer immunosuppressive, and biologic/targeted agents in LN.

Expert opinion

Early combination of conventional regimens with anti-B cell activation factor (anti-BAFF) or calcineurin inhibitors (CNIs) enhances the therapeutic effect without increasing serious adverse events in LN. However, combining anti-CD20 and anti-BAFF biologics appears to be less promising from the results of clinical trials. Initial combination strategy may be more cost-effective for patients at risk of treatment failure and renal function deterioration. With the availability of more options, the treat-to-target approach in LN is increasingly feasible and further studies are needed to compare the step-up and step-down approaches in the treatment of LN.

KEYWORDS:

• Anti-BAFF
• Anti-CD20
• belimumab
• biologics
• calcineurin
• lupus nephritis
• rituximab

Article highlights

• Cocktail immunosuppressive therapy of lupus nephritis (LN) may enhance efficacy and allow dosage reduction through a synergistic effect of individual drugs.

• Early combination of anti-BAFF or the calcineurin inhibitors with standard of care (SOC) increases the renal response rates of LN without causing more toxicities.

• The combination of anifrolumab and obinutuzumab with SOC appears to be promising in phase II clinical trials.

• Although the combination of anti-BAFF and anti-CD20 delays the repopulation of autoreactive B cells, clinical data are less promising in LN, and further evaluation is warranted.

• The initial combination strategy may be more cost-effective in LN patients who are at risk of treatment failure or renal function deterioration.

• The choice of novel therapies in LN should be individualized based on level of evidence, cost-effectiveness, extra-renal activity, expected treatment adherence and tolerability, medical comorbidities, risk of toxicity and safety during conception.

Declaration of interest

C.C. Mok received one-off speaker’s honoraria from GSK and Pfizer during the APLAR meeting in November 2022. The author has no other 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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.