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Hospital Circular 10 /2005

Date Issued: 31 May 2005

Distribution: Public Hospitals

Subject: Highly Specialised Drugs Program

We have had recent advice from the Commonwealth Government of changes to the Highly Specialised Drugs Program, effective 1 June 2005.

1. AMENDED RESTRICTION

INFLIXIMAB

NOTE:
Any queries concerning the arrangements to prescribe infliximab may be directed to the Health Insurance Commission (HIC) on 1800 005 750 (hours of operation 8 a.m. to 5 p.m. EST Monday to Friday).

Written applications for authority to prescribe infliximab should be forwarded to:
Health Insurance Commission
Prior Written Approval of Specialised Drugs
Reply Paid 9826
GPO Box 9826
HOBART TAS 7001

Further prescribing information is on the HIC website at www.hic.gov.au.

NOTE:
The following information applies to the prescribing under the Pharmaceutical Benefits Scheme (PBS) of the tumour necrosis factor (TNF) alfa antagonists (adalimumab, etanercept and infliximab) and the interleukin-1 inhibitor (anakinra) for adult patients with severe rheumatoid arthritis.

Patients are eligible for PBS-subsidised treatment with only 1 of the above biological disease modifying anti-rheumatic drugs (bDMARDs) at any 1 time.

1. Patients who have received no prior PBS-subsidised bDMARD treatment at 1 December 2004.

From 1 December 2004, the arrangements for prescribing the bDMARDs on the PBS have been amended to allow patients to commence a single cycle of bDMARD treatment that allows them to trial any number of bDMARDs without having to experience a disease flare when swapping between alternate bDMARDs. Within a single treatment cycle, patients may continue to receive long-term treatment with a bDMARD while they continue to show a response to therapy.

Once patients have either failed, or ceased to respond to, treatment with a maximum of 3 bDMARDs, they are deemed to have completed a single treatment cycle and they must have, at a minimum, a 5 year break in PBS-subsidised bDMARD therapy before they are eligible to commence the next cycle. The 5-year period will be measured from the date the last prescription for PBS-subsidised bDMARD treatment was approved in the most recent cycle to the date of the application for initial treatment with a bDMARD under the new cycle.

Patients who have failed treatment with fewer than 3 bDMARDs within a particular treatment cycle, and where a period of less than 5 years duration has elapsed since the patient's previous course of PBS-subsidised bDMARD treatment in that cycle, may commence a further course of bDMARD treatment within that same treatment cycle.

Patients who have failed treatment with fewer than 3 bDMARDs within a particular treatment cycle, and who have had a break in PBS-subsidised therapy of 5 years or more, are eligible to commence a new treatment cycle.

There is no limit to the number of treatment cycles a patient may undertake in their lifetime.

If patients fail to respond to a particular bDMARD within a single treatment cycle, they are not eligible to receive further PBS-subsidised treatment with that drug until they commence the next cycle.

2. Patients who have received PBS-subsidised TNF-alfa antagonist treatment prior to 1 December 2004.

Patients who commenced PBS-subsidised TNF-alfa antagonist therapy prior to 1 December 2004 are considered to be in their first cycle of bDMARD treatment on 1 December 2004.

Patients who have failed to respond to prior PBS-subsidised treatment with fewer than 3 TNF-alfa antagonists at the time the first application for treatment is made on or after 1 December 2004, will be subject to the same conditions applying to new patients detailed above.

Therefore, patients who have failed:

(a) 1 TNF-alfa antagonist will be eligible to trial further PBS-subsidised treatment with a bDMARD they have not failed in their first treatment cycle, until they fail to demonstrate a response to no more than another 2 bDMARDs;

(b) 2 TNF-alfa antagonists will be eligible to trial further PBS-subsidised treatment with a bDMARD they have not failed in their first treatment cycle, until they fail to demonstrate a response to no more than 1 other bDMARD.

Patients who have failed PBS-subsidised treatment with 3 TNF-alfa antagonists prior to 1 December 2004 or at the first assessment required after this date, will be eligible to trial PBS-subsidised treatment with anakinra if they wish. However, if they fail to demonstrate a response to anakinra, they will not be able to trial any further PBS-subsidised bDMARD treatment until a minimum of 5 years has elapsed from the date that the prescription for the last course of anakinra therapy was approved. Arrangements to allow these patients to fail 4 bDMARDs will only be in place for the first treatment cycle. For subsequent cycles, patients will cease to be eligible to receive PBS-subsidised bDMARD treatment once they have failed to demonstrate a response to a maximum of 3 bDMARDs.

Any queries on these arrangements should be forwarded to the HIC.

3. Information relevant to all patients.

(a) Initial treatment.

Applications for initial treatment should be made where:

(i) patients have received no prior PBS-subsidised bDMARD treatment and wish to commence such therapy; or

(ii) patients have received prior PBS-subsidised (initial or continuing) bDMARD therapy and wish to trial an alternate agent [further details are under 'Swapping therapy' below]; or

(iii) patients wish to re-commence treatment with a specific bDMARD following a break in PBS-subsidised therapy with that specific agent.

All applications for initial treatment will be limited to provide for a maximum of 16 weeks of therapy for all agents except for infliximab, for which a maximum of 22 weeks will be authorised. It is recommended that patients be reviewed in the month prior to completing their course of initial treatment to ensure uninterrupted bDMARD supply.

Patients must be assessed for response to any course of PBS-subsidised initial treatment following a minimum of 12 weeks of therapy and this assessment must be submitted to the HIC no later than 4 weeks from the date that course was ceased. Where a response assessment is not submitted to the HIC within these timeframes, patients will be deemed to have failed to respond to treatment with that bDMARD.

(b) Continuing treatment.

Following the completion of an initial treatment course with a specific bDMARD, patients may qualify to receive up to 24 weeks of continuing treatment with that drug providing they have demonstrated an adequate response to treatment. Patients are eligible to receive continuing bDMARD treatment with the same drug in courses of up to 24 weeks providing they continue to sustain the response.

Patients must be assessed for response to a course of continuing therapy, and the assessment must be submitted to the HIC no later than 4 weeks from the date that course was ceased. Where a response assessment is not submitted to the HIC within these timeframes, patients will be deemed to have failed to respond to treatment with that bDMARD.

(c) Swapping therapy.

Once an authority for initial treatment with the first PBS-subsidised bDMARD is approved, patients may swap to an alternate bDMARD without having to re-qualify with respect to either the indices of disease severity (i.e. erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) level, and active joint count) or the prior non-bDMARD therapy requirements. However, the requirement for concomitant treatment with methotrexate, where it applies, must be met for each bDMARD trialed.

Patients may swap to an alternate bDMARD at any time, regardless of whether they are receiving therapy (initial or continuing) with a bDMARD at the time of the application or not.

Patients may alternate between therapy with any bDMARD of their choice (1 at a time) providing:

(i) they have not received PBS-subsidised treatment with that particular bDMARD previously; or

(ii) they have demonstrated an adequate response to that particular bDMARD if they have previously trialed it on the PBS.

Therefore, to maximise the choice of bDMARD patients may alternate between, it is important that patients are assessed for response to every course of treatment approved, within the timeframes specified in the relevant restriction.

To avoid confusion, applications for patients who wish to swap to an alternate bDMARD should be accompanied by the approved authority prescription or remaining repeats for the bDMARD the patient is ceasing.

(d) Baseline measurements to determine response.

The HIC will determine whether a response to treatment has been demonstrated based on the baseline measurements of the indices of disease severity submitted with the first authority application for a bDMARD. However, prescribers may provide new baseline measurements any time that an initial treatment authority is submitted within a treatment cycle and the HIC will assess response according to these revised baseline measurements.

To ensure consistency in determining response, the same indices of disease severity used to establish baseline at the commencement of treatment with each initial treatment application must be provided for all subsequent continuing treatment applications. Therefore, where only an ESR or CRP level is provided at baseline, an ESR or CRP level respectively must be provided to determine response. Similarly, where the baseline active joint count is based on total active joints (i.e. more than 20 active joints), response will be determined according to a reduction in the total number of active joints.

(e) Re-commencement of treatment after a 5-year break in PBS-subsidised therapy.

Patients who wish to trial a second or subsequent treatment cycle following a break in PBS-subsidised bDMARD therapy of at least 5 years, must re-qualify for initial treatment with respect to both the indices of disease severity. Patients must have received treatment with at least 1 non-biological DMARD, at an adequate dose, for a minimum of 3 months at the time the ESR or CRP levels and the active joint counts are measured.

Public and private hospital authority required

Application for initial PBS-subsidised treatment with infliximab, in combination with methotrexate at a dose of at least 7.5 mg weekly, by a rheumatologist or clinical immunologist with expertise in the management of rheumatoid arthritis, of adults who:

(a) have severe active rheumatoid arthritis; and

(b) have received no prior PBS-subsidised treatment with a bDMARD for this condition in this treatment cycle; and

(c) have failed to achieve an adequate response to the following treatments:

(i) methotrexate at a dose of at least 20 mg weekly; and

(ii) methotrexate (at a minimum dose of 7.5 mg weekly), in combination with 2 other non-biological disease modifying anti-rheumatic drugs (DMARDs), for a minimum of 3 months;

and

(iii) a minimum of 3 months' treatment with:

- leflunomide alone; or

- leflunomide in combination with methotrexate; or

- cyclosporin

If treatment with any of the above-mentioned drugs is contraindicated according to the relevant TGA-approved Product Information, or intolerance of a severity necessitating permanent treatment withdrawal develops during the relevant period of use, the patient is exempted from demonstrating an inadequate response to that particular agent(s) only. Details of the contraindications or intolerance, including the degree of toxicity, must be provided at the time of application.

The following initiation criteria indicate failure to achieve an adequate response and must be demonstrable in all patients at the time of the initial application:

an elevated erythrocyte sedimentation rate (ESR) greater than 25 mm per hour or a C-reactive protein (CRP) level greater than 15 mg per L;

AND either

(i) a total active joint count of at least 20 active (swollen and tender) joints; or

(ii) at least 4 active joints from the following list of major joints:

- elbow, wrist, knee and/or ankle (assessed as swollen and tender); and/or

- shoulder and/or hip (assessed as pain in passive movement and restriction of passive movement, where pain and limitation of movement are due to active disease and not irreversible damage such as joint destruction or bony overgrowth).

If the above requirement to demonstrate an elevated ESR or CRP cannot be met, the application must state the reasons why this criterion cannot be satisfied.

The authority application must be made in writing and must include:

(1) a completed authority prescription form; and

(2) a completed Biological DMARD PBS Authority Application for Use in the Treatment of Rheumatoid Arthritis - Supporting Information Form [may be downloaded from the HIC website (www.hic.gov.au/providers/forms/pbs/medical_practitioners.htm)] which includes details of the patient's ESR and CRP measurements and the patient's active joint count which must have been assessed no earlier than 1 month prior to the date of application; and

(3) a copy of the signed patient acknowledgement form which may be downloaded from the HIC website (www.hic.gov.au/providers/forms/pbs/medical_practitioners.htm). Completion of this form declares that the patient understands and acknowledges that, within a single treatment cycle, PBS-subsidised treatment with any biological DMARD will cease if they do not demonstrate the response to treatment required to support continuation of PBS-subsidised treatment at any assessment where a response must be demonstrated.

At the time of the authority application, medical practitioners should request the appropriate quantity of vials, based on the weight of the patient, to provide sufficient for a single infusion at a dose of 3 mg per kg. Up to a maximum of 3 repeats may be authorised.
Where fewer than 3 repeats are requested at the time of the initial application, authority approvals for sufficient repeats to complete a maximum of 22 weeks of treatment may be requested by telephone by contacting the HIC on 1800 005 750 (hours of operation 8 a.m. to 5 p.m. EST Monday to Friday).

Patients who fail to demonstrate a response to treatment with infliximab under this restriction will not be eligible to receive further PBS-subsidised treatment with this drug, in this treatment cycle. Patients may re-trial infliximab after a minimum of 5 years have elapsed between the date the last prescription for a PBS-subsidised bDMARD was approved in this cycle and the date of the first application under the new cycle.

Public and private hospital authority required

Application for an initial course of PBS-subsidised treatment with infliximab, in combination with methotrexate at a dose of at least 7.5 mg weekly, by a rheumatologist or clinical immunologist with expertise in the management of rheumatoid arthritis, of adults who:

(a) have severe active rheumatoid arthritis; and

(b) have received prior PBS-subsidised bDMARD treatment for this condition in this treatment cycle and are eligible to receive further bDMARD therapy.

Patients who were commenced on treatment with infliximab prior to 1 December 2004 and who have received methotrexate at a dose of less than 7.5 mg per week will be able to continue to receive PBS-subsidised treatment with infliximab in combination with methotrexate at this lower dose for the duration of the first bDMARD treatment cycle. For subsequent treatment cycles, patients must receive concomitant methotrexate at a dose of at least 7.5 mg weekly.

Applications for patients who have received PBS-subsidised treatment with infliximab within this treatment cycle and who wish to re-commence therapy with this drug within this same cycle, must be accompanied by evidence of a response to the patient's most recent course of PBS-subsidised infliximab treatment, within the timeframes specified below.

Where the most recent course of PBS-subsidised infliximab treatment was approved under either of the initial treatment restrictions (i.e. for patients with no prior PBS-subsidised bDMARD therapy or, under this restriction, for patients who have received previous PBS-subsidised bDMARD therapy), patients must have been assessed for response following a minimum of 12 weeks of therapy. This assessment must be provided to the HIC no later than 4 weeks from the date that course was ceased.

Where the most recent course of PBS-subsidised infliximab treatment was approved under the continuing treatment criteria, patients must have been assessed for response, and the assessment must be submitted to the HIC no later than 4 weeks from the date that course was ceased.

The authority application must be made in writing and must include:

(1) a completed authority prescription form; and

(2) a completed Biological DMARD PBS Authority Application for Use in the Treatment of Rheumatoid Arthritis - Supporting Information Form [may be downloaded from the HIC website (www.hic.gov.au/providers/forms/pbs/medical_practitioners.htm)].

At the time of the authority application, medical practitioners should request the appropriate quantity of vials, based on the weight of the patient, to provide sufficient for a single infusion at a dose of 3 mg per kg. Up to a maximum of 3 repeats may be authorised.

Where fewer than 3 repeats are requested at the time of the initial application, authority approvals for sufficient repeats to complete a maximum of 22 weeks of treatment may be requested by telephone by contacting the HIC on 1800 005 750 (hours of operation 8 a.m. to 5 p.m. EST Monday to Friday).

Patients who fail to demonstrate a response to treatment with infliximab under this restriction will not be eligible to receive further PBS-subsidised treatment with this drug, in this treatment cycle. Patients may re-trial infliximab after a minimum of 5 years have elapsed between the date the last prescription for a PBS-subsidised bDMARD was approved in this cycle and the date of the first application under the new cycle.

Once patients fail to respond to treatment with 3 bDMARDs, they are deemed to have completed this treatment cycle and must cease PBS-subsidised therapy. These patients may re-commence a new bDMARD treatment cycle after a minimum of 5 years have elapsed between the date the last prescription for a PBS-subsidised bDMARD was approved in this cycle and the date of the first application under the new cycle.

Public and private hospital authority required

Initial PBS-subsidised supply for continuing treatment with infliximab, in combination with methotrexate at a dose of at least 7.5 mg weekly, by a rheumatologist or clinical immunologist with expertise in the management of rheumatoid arthritis, of adults who:

(a) have severe active rheumatoid arthritis; and

(b) were receiving treatment with infliximab prior to 1 March 2005; and

(c) failed to qualify for PBS-subsidised therapy after 1 November 2003 due to testing negative for rheumatoid factor; and

(d) have demonstrated a response as specified in the criteria for continuing PBS-subsidised treatment with infliximab.

Medical practitioners who wish to apply for authority to prescribe a bDMARD for patients who commenced treatment with infliximab prior to 1 March 2005 and who have not demonstrated a response to treatment should contact the HIC on 1800 005 750.

The authority application must be in writing and must include sufficient information to determine the patient's eligibility. The date of assessment must be provided.

At the time of the authority application, medical practitioners should request the appropriate quantity of vials, based on the weight of the patient, to provide sufficient for a single infusion at a dose of 3 mg per kg. Up to a maximum of 2 repeats may be authorised.

Patients who fail to demonstrate a response to treatment with infliximab under this restriction will not be eligible to receive further PBS-subsidised treatment with this drug, in this treatment cycle. Patients may re-trial infliximab after a minimum of 5 years have elapsed between the date the last prescription for a PBS-subsidised bDMARD was approved in this cycle and the date of the first application under the new cycle.

Once patients fail to respond to treatment with 3 bDMARDs, they are deemed to have completed this treatment cycle and must cease PBS-subsidised therapy. These patients may re-commence a new bDMARD treatment cycle after a minimum of 5 years have elapsed between the date the last prescription for a PBS-subsidised bDMARD was approved in this cycle and the date of the first application under the new cycle.

Public and private hospital authority required

Continuing PBS-subsidised treatment with infliximab, in combination with methotrexate at a dose of at least 7.5 mg weekly, by a rheumatologist or clinical immunologist with expertise in the management of rheumatoid arthritis, of adults:

(a) who have severe active rheumatoid arthritis; and

(b) who have demonstrated an adequate response to treatment with infliximab; and

(c) whose most recent course of PBS-subsidised bDMARD treatment in this treatment cycle was with infliximab.

An adequate response to treatment is defined as:

an ESR no greater than 25 mm per hour or a CRP level no greater than 15 mg per L or either marker reduced by at least 20% from baseline;

AND either of the following:

(i) a reduction in the total active (swollen and tender) joint count by at least 50% from baseline, where baseline is at least 20 active joints; or

(ii) a reduction in the number of the following major active joints, from at least 4, by at least 50%:

- elbow, wrist, knee and/or ankle (assessed as swollen and tender); and/or

- shoulder and/or hip (assessed as pain in passive movement and restriction of passive movement, where pain and limitation of movement are due to active disease and not irreversible damage such as joint destruction or bony overgrowth).

Patients who were commenced on treatment with infliximab prior to 1 December 2004 and who have received methotrexate at a dose of less than 7.5 mg per week will be able to continue to receive PBS-subsidised treatment with infliximab in combination with methotrexate at this lower dose for the duration of the first bDMARD treatment cycle. For subsequent treatment cycles, patients must receive concomitant methotrexate at a dose of at least 7.5 mg weekly.

The authority application must be made in writing and must include:

(1) a completed authority prescription form; and

(2) a completed Biological DMARD PBS Authority Application for Use in the Treatment of Rheumatoid Arthritis - Supporting Information Form [may be downloaded from the HIC website (www.hic.gov.au/providers/forms/pbs/medical_practitioners.htm)].

All applications for continuing treatment with infliximab must include a measurement of response to the prior course of therapy. This assessment must be provided to the HIC no later than 4 weeks from the cessation of that treatment course. If the application is the first application for continuing treatment with infliximab, it must be accompanied by an assessment of response to a minimum of 12 weeks of treatment with an initial treatment course.

At the time of the authority application, medical practitioners should request the appropriate quantity of vials, based on the weight of the patient, to provide sufficient for a single infusion at a dose of 3 mg per kg. Up to a maximum of 2 repeats may be authorised.

Where fewer than 2 repeats are requested at the time of the application, authority approvals for sufficient repeats to complete a maximum of 24 weeks of treatment may be requested by telephone by contacting the HIC on 1800 005 750 (hours of operation 8 a.m. to 5 p.m. EST Monday to Friday).

Patients who fail to demonstrate a response to treatment with infliximab under this restriction will not be eligible to receive further PBS-subsidised treatment with this drug, in this treatment cycle. Patients may re-trial infliximab after a minimum of 5 years have elapsed between the date the last prescription for a PBS-subsidised bDMARD was approved in this cycle and the date of the first application under the new cycle.

Once patients fail to respond to treatment with 3 bDMARDs, they are deemed to have completed this treatment cycle and must cease PBS-subsidised therapy. These patients may re-commence a new bDMARD treatment cycle after a minimum of 5 years have elapsed between the date the last prescription for a PBS-subsidised bDMARD was approved in this cycle and the date of the first application under the new cycle.

There has been no change to the ankylosing spondylitis indication.

Changes notified by hospital circular will be updated in the Guidelines on the internet and the relevant claim forms amended.

WEB SITE ADDRESS: www.health.vic.gov.au/hsdp

Noreen Dowd
Director, Programs
Metropolitan Health & Aged Care Services