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.