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Abstract: TH-PO483

Ofatumumab in Rituximab-Resistant and Rituximab-Intolerant Patients With Membranous Nephropathy

Session Information

Category: Glomerular Diseases

  • 1303 Glomerular Diseases: Clinical‚ Outcomes‚ and Trials

Authors

  • Podesta', Manuel Alfredo, Universita degli Studi di Milano, Milano, Lombardia, Italy
  • Portalupi, Valentina, Aziende Socio Sanitarie Territoriale Papa Giovanni XXIII, Bergamo, Lombardia, Italy
  • Gennarini, Alessia, Aziende Socio Sanitarie Territoriale Papa Giovanni XXIII, Bergamo, Lombardia, Italy
  • Villa, Alessandro, Istituto di Ricerche Farmacologiche Mario Negri Centro Aldo e Cele Dacco, Ranica, Lombardia, Italy
  • Rubis, Nadia, Istituto di Ricerche Farmacologiche Mario Negri Centro Aldo e Cele Dacco, Ranica, Lombardia, Italy
  • Remuzzi, Giuseppe, Istituto di Ricerche Farmacologiche Mario Negri Centro Aldo e Cele Dacco, Ranica, Lombardia, Italy
  • Ruggenenti, Piero Luigi, Aziende Socio Sanitarie Territoriale Papa Giovanni XXIII, Bergamo, Lombardia, Italy
Background

Rituximab (RTX) has become the mainstay therapy for patients with membranous nephropathy (MN) at high risk of progression to kidney failure. However, this treatment is effective only in ~65% of patients, and exposure to repeated RTX infusions may be complicated by hypersensitivity reactions, which contraindicate re-treatment. Ofatumumab, a human anti-CD20 antibody with higher cytotoxicity, could overcome these limitations.

Methods

In this retrospective cohort study, we enrolled adult patients with MN who either experienced hypersensitivity reactions (RTX-intolerant,n=5) or failed to achieve complete or partial remission after RTX administration (RTX-resistant,n=12), and were treated with ofatumumab as a rescue therapy (50-300 mg).

Results

After a median follow-up time of 1 year, 58.8% of patients achieved complete or partial remission of the nephrotic syndrome (41.7% in RTX-resistant and 100% in RTX-intolerant). In patients with positive anti-PLA2R at baseline (n=12), 58.3% achieved serological remission during the follow-up (50% in RTX-resistant and 100% in RTX-intolerant).Reduction in urinary protein excretion was closely mirrored by an increase in serum albumin levels (Figure 1).Measured GFR increased by a median of 13.4% at 24 months compared to baseline.There were 14 non-serious infusion-related adverse events in 9 patients, all of which completely resolved.

Conclusion

Ofatumumab may represent a viable option for the treatment of MN patients who are resistant or intolerant to RTX.

Baseline characteristics
 Overall
(n =17)
RTX-Resistant
(n = 12)
RTX-Intolerant
(n = 5)
Age (years)51.0±13.653.3±14.545.6±10.3
mGFR (mL/min/1.73m2)52.1 [38.6; 73.4]41.9 [37.8; 72.8]67.4 [55.8; 83.4]
Serum Albumin (g/dL)2.5±0.52.5±0.52.6±0.6
Urinary Protein (g/24h)9.0±4.310.3±4.36.2±2.8
Serum Anti-PLA2R (RU/mL)66 [14; 117]66 [11; 146]53 [18; 89]
Ofatumumab Dose (mg)300 [100; 300]300 [63; 300]300 [100; 300]
MN Onset (years)9.9±5.18.5±5.313.2±2.4

(L) Cumulative incidence of CR/PR in RTX-intolerant and -resistant patients. (R) % change in proteinuria and serum albumin after Ofatumumab.