Iguratimod as an alternative induction therapy for refractory lupus nephritis: a preliminary investigational study

Abstract

Objectives: Iguratimod, a novel immunomodulatory agent for rheumatoid arthritis, has been shown to be effective against murine lupus. The aim of this study was to make a preliminary evaluation of the efficacy and safety of iguratimod as salvage therapy in patients with refractory lupus nephritis (LN). Methods: We enrolled eligible patients with refractory LN, which we defined as having failed or relapsed on at least two immunosuppressant agents. After enrollment, we substituted iguratimod (25 mg twice daily) for their previous immunosuppressant agents without increasing the dose of steroids. The primary outcome was complete/ partial remission (PR/CR) at week 24. Patients who achieved remission continued iguratimod as maintenance therapy over an extended follow-up. Results: The study cohort comprised 14 patients with refractory LN, 10 of whom had recent treatment failure and 4 repeated relapses with inadequate initial responses. At enrollment, none of the patients had detectable evidence of extra-renal involvement. The median prednisone dosage was 10 mg/d (IQR 0-10 mg/day). Thirteen patients were eligible for response evaluation, with one patient missed. The renal response rate was 92.3% (12/13) at week 24, with 38.5% (5/13) achieving CR and 53.8% (7/13) achieving PR. We then continued to follow up the responding patients for up to 144 weeks. Twenty-five percent of the patients (3/12) had renal relapse after initial PR. The estimated glomerular filtration rate of all patients maintained stable during follow-up. One patient had a severe adverse reaction (anemia) but recovered fully after stopping iguratimod. Conclusions: Our study supports the potential of iguratimod for treatment of refractory LN. Iguratimod could be a promising candidate drug for this condition.

Comparison of iguratimod and conventional cyclophosphamide with sequential azathioprine as treatment of active lupus nephritis: study protocol for a multi-center, randomized, controlled clinical trial (iGeLU study)

“…In the first 24 weeks of the trial, IGU is compared with cyclophosphamide as an induction therapy, and in the second 24 weeks, IGU is compared with azathioprine as a maintenance therapy. In the previous observatory LN study, over 90% refractory LN patients responded to iguratimod monotherapy without any steroids increasing in the first 24 weeks of treatment [ 18 ]. Given to this outstanding effectiveness of IGU, the result of this study is expectable and promising.…”

“…In a preclinical study on lupus, iguratimod prevented autoimmune nephritis in MRL/lpr mice, decreased the amount of proteinuria, and reduced immune complex deposition [ 17 ]. Beyond expectation in a recent observational study, over 90% of thirteen refractory LN patients responded to iguratimod monotherapy in 24 weeks, with no steroids dose increasing or any other medication add-on during the entire follow-up [ 18 ].…”

New developments in systemic lupus erythematosus

“…Its modulatory effect is through B cell differentiation. In an open-label study [ 48 ], 14 refractory lupus nephritis patients, 10 of whom had recent treatment failure and four had repeated relapses with inadequate initial responses, were enrolled. Out of 12 patients, five had a complete and seven a partial renal response, of whom three had a relapse within 144 weeks of follow-up.…”

Efficacy and Safety of Iguratimod Supplement to the Standard Immunosuppressive Regimen in Highly Mismatched Renal Transplant Recipients: A Pilot Study

“…It suppresses antibody production by directly inhibiting the NF-κB pathway in B cells ( 7 , 8 ). Studies have highlighted its protective effects on lupus nephropathy in a mouse model and a small clinical study ( 9 , 10 ), and a recent randomized clinical trial also showed its efficacy against primary Sjögren’s syndrome ( 11 ). In a previous study, we found that IGU mitigated antibody-mediated rejection (ABMR) in a pre-sensitized mouse transplant model (unpublished), which is not surprising given the similarities between autoimmune diseases and graft rejection.…”