Telitacicept for minimal change disease

Minimal change disease (MCD) is a common pathological type of idiopathic nephrotic syndrome. ¹ The first‐line therapy is prednisone, ² but steroid‐sensitive forms frequently relapse. Telitacicept, a B lymphocyte stimulator and a proliferation‐inducing ligand dual inhibitor, has been investigated for several autoimmune diseases. ³

A 44‐year‐old female presented with edema of both lower extremities for 20 days in July 2020. Urine protein was +++, 24‐h urine protein was 5055 mg, and serum albumin was 25.5 g/L; other laboratory test results were unremarkable. The patient received Tripterygium wilfordii, irbesartan, and antihydropic diuretic agents for 2 months. The edema was not completely alleviated. Renal pathology showed no obvious pathological changes. Immunofluorescence revealed no obvious immunofluorescence distribution. Electron microscopy showed a diffuse foot process fusion of the podocytes, swelling of renal tubular epithelial cells and organelle, and interstitial focal edema, indicating MCD. Prednisone 30 mg/day and tacrolimus 1 mg/day led to complete remission after 8‐month treatment, but the disease recurred after reducing the prednisone dose. The patient refused high‐dose prednisone or hospitalization. Telitacicept 160 mg/week was initiated in January 2022, along with prednisone 30 mg/day. After 4‐week treatment, the patient was in complete remission. Prednisone was rapidly reduced to 5 mg/day. Maintenance telitacicept lasted 6 months, reduced to 80 mg every 2 weeks. Her condition was stabilized without adverse reactions or disease recurrence (Figure 1).

FIGURE 1.

(A) Drug use and changes of the main examination indexes. (1) Telitacicept 160 mg, once every 7 days. (2) Telitacicept 80 mg, once every 7 days. (3) Telitacicept 80 mg, once every 10 days. (4) Telitacicept 80 mg, once every 14 days. (B) Reduction of prednisone dose after initiating telitacicept treatment.

Designing treatment schemes for adults with MCD is challenging because of the high recurrence rate (65%–80%). ² The 2021 KDIGO guidelines recommend first‐line high‐dose oral glucocorticoids not exceeding 16 weeks. For frequently relapsing or steroid‐dependent MCD, cyclophosphamide, rituximab, calcineurin inhibitors, or mycophenolic acid analogs are recommended but risks are involved, such as reproductive toxicity for cyclophosphamide, nephrotoxicity for long‐term calcineurin inhibitors, and hypogammaglobulinemia for rituximab. ²

In this case, rituximab was refused by the patient when disease relapsed since it required short‐term hospitalization at each administration. Considering prior long‐term prednisone use, she was advised to receive telitacicept, which was conveniently administered by subcutaneous injection. Telitacicept inhibits the differentiation and maturation of B lymphocytes and reduces the production of autoantibodies. ³ , ⁴ After 4‐week treatment, the patient showed normal urine protein, and the prednisone dosage was rapidly reduced from 30 to 5 mg/day, and disease remission was maintained for 6 months. The satisfactory therapeutic effects of telitacicept in treating immune diseases have been reported in several clinical trials. ³ In a multicenter phase II clinical trial (NCT04291781), patients with IgA nephropathy after optimized RAS blocker therapy were administered telitacicept 240 mg/week for 24 weeks, and the 24‐h urine protein levels decreased by 49% from baseline, with a favorable safety profile.

In conclusion, we present an MCD patient achieving complete response with telitacicept who had a recurrence after long‐term prednisone and tacrolimus. Telitacicept might be a new treatment option for MCD patients with poor response to long‐term glucocorticoids. Still, the clinical application of telitacicept remains in its exploratory stage, and this case provided preliminary evidence for conducting subsequent clinical trials of telitacicept in the treatment of MCD.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflict of interest.