ofatumumab for rituximab-resistant nephrotic syndrome
TRANSCRIPT
Ofatumumab For Rituximab-resistant
Nephrotic Syndrome
By :Dr.Hemat Afifi Sherif
March 27, 2014
Rituximab was found to be a promising agent in managing SRNS
that was resistant to alkylating agents and calcineurin inhibitors.
The steroid-resistant nephrotic syndrome
(SRNS)
children with
Is challenging
with a 6-year history of SRNS
had resistance to all available standard
drugs, including two courses of
Rituximab.
19-year-old girl
Diagnoses
Focal segmental
glomerulosclerosis
History
After the withdrawal of glucocorticoids,
she continued to have nephrotic-range
proteinuria
She also had a 2-year history of
chronic lymphocytic leukemia LLC((
She Was Receiving
Ofatumumab
o A humanized anti-CD20monoclonal antibody approved
by FDA for the treatment of
multidrug-resistant CLL
o With efficacy against rituximab-
resistant B-cell cancers.
Ofatumumab
After the first dose
the proteinuria improved
After the third dose
the hypoalbuminemia resolved
After the sixth dose
Remission was achieved
ratio of urinary protein to creatinine<
0.2
Therapy with ofatumumab
produced a dramatic response in
the patient's renal status .
Initial Resistance late resistance
with rituximab-resistant idiopathic SRNS
• Renal-biopsy specimens obtained before enrollment
showed :
minimal-change disease
Focal Segmental Glomerulosclerosis
The children had previously received multiple medications including
two courses of rituximab but continued to have nephrotic-range
proteinuria. At the time of study enrollment, the
children were receiving only Ramipril.
History
Ofatumumab was administered at a dose of :
For the first week• 300 mg per 1.73 m2 of body-surface area
Weekly for five infusions • 2000 mg per 1.73 m2
After The Sixth Dose
On the basis of the index patient's response after the sixth dose
•Remission was achieved :
After The Fourth Dose
All the patients received a total of six doses.
Two months later
Had A Relapse
Treated successfully with oral glucocorticoids
Resulted in partial remission (Range of protein-to-creatinine
ratio, 0.2 to 2.0, with both substances measured in milligrams)
At 6 months of follow-up
Remission was maintained in the other three patients
without the use of glucocorticoids or any other glucocorticoid-sparing agent during the follow-up period.
For all five patientsthe mean protein-to-creatinine ratio declined from
13.00 at baseline to
1. 0.102. 0.183. 0.21
At 6 weeksAt 6 monthsAt 9 month
The mean estimated glomerular filtration rate(GFR) improved :from 72.6 ml per minute per 1.73 m2 at
baseline to:
1. 93.42. 94.03. 85.4
At 6 weeksAt 6 monthsAt 9 month
the mean serum albumin level increased
from 1.2g/dl to
1. 3.72. 3.53. 3.1
At 6 weeksAt 6 monthsAt 9 month
Further studies are necessary to : confirm these observations to define the most effective dose
and safety of ofatumumab in managing SRNS.
one transient infusion reaction none of the patients had any serious
adverse events during the study period.