Access to rituximab for children with nephrotic syndrome

Medicines

Decision

PHARMAC is pleased to announce the decision to widen access to rituximab in DHB hospitals from 1 July 2016 for use in for children with steroid dependent, frequently relapsing and steroid resistant nephrotic syndrome.

The decision is as consulted on, with the exception of changes to the HML initiation restriction applying to:

  • steroid dependent nephrotic syndrome (SDNS) and frequently relapsing nephrotic syndrome (FRNS);
  • steroid resistant nephrotic syndrome (SRNS).

Details of the decision

From 1 July 2016 the following restrictions will apply to rituximab 100 mg per ml, 10 ml and 50 ml vials (Mabthera) for SDNS and FRNS in Section H of the Pharmaceutical Schedule as follows:

Restricted

Initiation – Steroid dependent nephrotic syndrome (SDNS) or frequently relapsing nephrotic syndrome (FRNS)

Nephrologist

Limited to 4 weeks treatment

All of the following:

  1. Patient is a child with SDNS* or FRNS*; and
  2. Treatment with steroids for at least a period of 3 months has been ineffective or associated with evidence of steroid toxicity; and
  3. Treatment with ciclosporin for at least a period of 3 months has been ineffective and/or discontinued due to unacceptable side effects; and
  4. Treatment with mycophenolate for at least a period of 3 months with no reduction in disease relapses; and
  5. The total rituximab dose used would not exceed the equivalent of 375 mg/ m2 of body surface area per week for a total of 4 weeks.

Note: Indications marked with a * are Unapproved indications.

Continuation - Steroid dependent nephrotic syndrome (SDNS) or frequently relapsing

nephrotic syndrome (FRNS)

Nephrologist

Limited to 4 weeks treatment

All of the following:

  1. Patient who was previously treated with rituximab for nephrotic syndrome*; and
  2. Treatment with rituximab was previously successful and has demonstrated sustained response for >6 months, but the condition has relapsed and the patient now requires repeat treatment; and
  3. The total rituximab dose used would not exceed the equivalent of 375 mg/ m2 of body surface area per week for a total of 4 weeks.

Note: Indications marked with a * are Unapproved indications.

From 1 July 2016 the following restrictions will apply to rituximab 100 mg per ml, 10 ml and 50 ml vials (Mabthera) for SRNS in Section H of the Pharmaceutical Schedule as follows:

Restricted

Initiation – Steroid resistant nephrotic syndrome (SRNS)

Nephrologist

Limited to 4 weeks treatment

All of the following:

  1. Patient is a child with SRNS* where treatment with steroids and ciclosporin for at least 3 months have been ineffective; and
  2. Treatment with tacrolimus for at least 3 months has been ineffective; and
  3. Genetic causes of nephrotic syndrome have been excluded; and
  4. The total rituximab dose used would not exceed the equivalent of 375 mg/ m2 of body surface area per week for a total of 4 weeks.

Note: Indications marked with a * are Unapproved indications.

Continuation - Steroid resistant nephrotic syndrome (SRNS)

Nephrologist

Limited to 4 weeks treatment

All of the following:

  1. Patient who was previously treated with rituximab for nephrotic syndrome*; and
  2. Treatment with rituximab was previously successful and has demonstrated sustained response for greater than 6 months, but the condition has relapsed and the patient now requires repeat treatment; and
  3. The total rituximab dose used would not exceed the equivalent of 375 mg/ m2 of body surface area per week for a total of 4 weeks.

Note: Indications marked with a * are Unapproved indications.

  • The price of rituximab will remain unchanged.

Feedback received

Feedback is a vital part to the decision making process, and we appreciate all of the feedback that we received and acknowledge the time people took to respond.

All consultation responses received by 25 May 2016 were considered in their entirety in making a decision on the proposed changes. Most responses were supportive of the proposal, and the following issues were raised in relation to specific aspects of the proposal:

Theme Comment
Supportive of the proposal. Noted.
The proposal could be cost saving if dialysis can be avoided. PHARMAC analysis indicates this decision would be cost-saving to DHB hospitals if dialysis can be delayed or avoided.
Clinician feedback considered the proposed restrictions should be amended :
  • The addition of mycophenolate (MMF) as a line of therapy for SDNS and FRNS restriction would be appropriate. Respondent noted that 40-50% of these patients would remain in remission from MMF treatment.
  • To allow patients who have experienced significant adverse effects with ciclosporin to be added to criteria 3 of SDNS and FRNS Restriction. Considered some patients trialing ciclosporin in SDNS and FRNS may encounter significant adverse effects such as nephrotoxicity, hypotension and cosmetic effects. Therefore it would be inappropriate for these patients to continue ciclosporin when experiencing significant adverse events.
  • Patients with genetic causes of NS should be excluded from SRNS restriction criteria. Considered these could make up 25-35% of the SRNS patient group, and are typically immunosuppression resistant i.e. rituximab would not work for them.
  • Restrictions on dosing to be amended to 2 doses every 14 days per course. Following further discussion with PHARMAC staff, the wording was considered to be clinically appropriate and would give clinicians greater dosing flexibility.
  
Following consideration of this feedback, the proposed HML Restrictions have been amended  as follows (additions in bold): Initiation – Steroid dependent nephrotic syndrome (SDNS) or frequently relapsing nephrotic syndrome (FRNS) NephrologistLimited to 4 weeks treatmentAll of the following:
  1. Patient is a child with SDNS* or FRNS*; and
  2. Treatment with steroids for at least a period of 3 months has been ineffective or associated with evidence of steroid toxicity; and
  3. Treatment with ciclosporin for at least a period of 3 months has been ineffective and/or discontinued due to unacceptable side effects; and
  4. Treatment with mycophenolate for at least a period of 3 months with no reduction in disease relapses.
  5. The total rituximab dose used would not exceed the equivalent of 375 mg/m2 of body surface area per week for a total of 4 weeks.
Note: Indications marked with a * are Unapproved indications. Initiation – Steroid resistant nephrotic syndrome (SRNS)NephrologistLimited to 4 weeks treatmentAll of the following:
  1. Patient is a child with SRNS* where treatment with steroids and ciclosporin for at least 3 months have been ineffective; and
  2. Treatment with tacrolimus for at least 3 months has been ineffective; and
  3. Genetic causes of nephrotic syndrome have been excluded.
  4. The total rituximab dose used would not exceed the equivalent of 375 mg/ m2 of body surface area per week for a total of 4 weeks.
Note: Indications marked with a * are Unapproved indications.PHARMAC considers that the amended restrictions better reflect the intended patient group(s). No changes have been made to the renewal criteria.
Consideration should be given to widen access to rituximab in adults with nephrotic syndrome. PHARMAC’s Pharmacology and Therapeutics Advisory Committee (PTAC) considered that there is currently insufficient evidence to support the use of rituximab in adults with nephrotic syndrome.  PHARMAC would be willing to consider the use of rituximab for adults with nephrotic syndrome if further evidence becomes available.
Evidence is limited for this indication PTAC noted the evidence in support of the indication was mainly in children, and considered the quality of evidence reviewed was moderate in strength and low in quality. However PTAC considered there is a significant health need for this group of patients and delaying end-stage renal disease would be crucial for them. PTAC also noted this treatment was already an established practice at some DHB hospitals prior the introduction of the Hospital Medicines List and some children with NS had accessed this via the NPPA policy. The minutes can be found here:https://www.pharmac.govt.nz/assets/ptac-minutes-2015-08.pdf(external link)

More information

If you have any questions about this decision, you can email us at enquiry@pharmac.govt.nz.