Lupus nephritis (LN)

Active Ingredient: Obinutuzumab

Indication for Obinutuzumab

Population group: only adults (18 years old or older)
Therapeutic intent: Curative procedure

Obinutuzumab in combination with mycophenolate mofetil (MMF) is indicated for the treatment of adult patients with active Class III or IV, with or without concomitant Class V, lupus nephritis (LN).

For this indication, competent medicine agencies globally authorize below treatments:

1,000 mg initial infusion followed by 1,000 mg on Weeks 2, 24, 26, and thereafter 1,000 mg once every 6 months

For:

Dosage regimens

Intravenous, 1,000 milligrams obinutuzumab, one dose, over the duration of 2 weeks. Afterwards, intravenous, 1,000 milligrams obinutuzumab, one dose, over the duration of 22 weeks. Afterwards, intravenous, 1,000 milligrams obinutuzumab, one dose, over the duration of 2 weeks. Afterwards, intravenous, 1,000 milligrams obinutuzumab, one dose, over the duration of 6 months. Afterwards, intravenous, 1,000 milligrams obinutuzumab, once every 6 months.

Detailed description

The recommended dosage of obinutuzumab is 1 000 mg administered intravenously. Obinutuzumab should be used in combination with mycophenolate mofetil.

Dose of obinutuzumab for patients with Lupus Nephritis:

Dose numberTiming of treatmentDose
1Initial infusion1 000 mg
2Week 2
(two weeks after Dose 1)
1 000 mg
3Week 241 000 mg
4Week 26
(two weeks after Dose 3)
1 000 mg
5* and
thereafter
Every 6 months1 000 mg

* Dose 5 should be administered six months after Dose 4

The patient's condition and response should be evaluated at Week 76 and beyond, and an appropriate risk-benefit analysis should be made for continuation of therapy.

Delayed or missed doses

If a planned dose of obinutuzumab is missed, it should be administered as soon as possible - do not wait until the next planned dose. The schedule of administration should be adjusted to maintain the appropriate interval between doses.

Dose modifications during treatment

No dose reductions of obinutuzumab are recommended.

Dosage considerations

Obinutuzumab should be given as an intravenous infusion through a dedicated line after dilution. Obinutuzumab infusions should not be administered as an intravenous push or bolus.

The initial obinutuzumab infusion should be administered at the standard infusion rate.

Lupus nephritis: Standard infusion rate:

Dose numberTiming of treatmentRate of infusion
1Initial infusion
(1 000 mg)
Administer at a rate of 50 mg/hr. The rate of
infusion can be escalated in 50 mg/hr
increments every 30 minutes to a maximum of
400 mg/hr. For management of IRRs that
occur during infusion, refer to Management of
IRRs.
2Week 2 - two weeks after
Dose 1

(1 000 mg)
Administer at a rate of 100 mg/hr. The rate of
infusion can be escalated at a rate of
100 mg/hr every 30 minutes to a maximum of
400 mg/hr.
3Week 24
(1 000 mg)
4Week 26 - two weeks after
Dose 3

(1 000 mg)
5* and
thereafter
Every 6 months
(1 000 mg)

* Dose 5 should be administered six months after Dose 4

Management of IRRs

Management of IRRs may require temporary interruption, reduction in the rate of infusion, or treatment discontinuations of obinutuzumab as outlined below:

  • Grade 4 (life threatening): Infusion must be stopped and therapy must be permanently discontinued.
  • Grade 3 (severe): Infusion must be temporarily stopped and symptoms treated. Upon resolution of symptoms, the infusion can be restarted at no more than half the previous rate (the rate being used at the time that the IRR occurred) and, if the patient does not experience any further IRR symptoms, the infusion rate escalation can resume at the increments and intervals as appropriate for the treatment dose. The infusion must be stopped and therapy permanently discontinued if the patient experiences a second occurrence of a Grade 3 IRR.
  • Grade 1-2 (mild to moderate): The infusion rate must be reduced to half the rate that was used at the time of the reaction and symptoms treated. Infusion can be continued upon resolution of symptoms at the reduced rate for an additional 30 minutes. If the patient does not experience any further IRR symptoms, the infusion rate escalation can resume at the increments and intervals as appropriate for the treatment dose.

Active ingredient

Obinutuzumab

Obinutuzumab is a recombinant monoclonal humanised and glycoengineered Type II anti-CD20 antibody of the IgG1 isotype. It specifically targets the extracellular loop of the CD20 transmembrane antigen on the surface of non-malignant and malignant pre-B and mature B-lymphocytes. Glycoengineering of the Fc part of obinutuzumab results in higher affinity for FcγRIII receptors on immune effector cells such as natural killer cells, macrophages and monocytes as compared to non-glycoengineered antibodies.

Read more about Obinutuzumab

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