Renflexis

For the treatment of rheumatoid arthritis (RA) in patients who have severe active disease (greater than or equal to 5 swollen joints and rheumatoid factor positive and/or, anti-CCP positive, and/or radiographic evidence of rheumatoid arthritis) and have experienced failure, intolerance, or have a contraindication to adequate trials of disease-modifying anti-rheumatic drugs (DMARDs) treatment regimens, such as one of the following combinations of treatments:

A.  i) Methotrexate (20mg/week) for at least 3 months, AND
    ii) leflunomide (20mg/day) for at least 3 months, in addition to
   iii) an adequate trial of at least one combination of DMARDs for 3 months; OR

B.  i) Methotrexate (20mg/week) for at least 3 months, AND
    ii) leflunomide in combination with methotrexate for at least 3 months; OR

C.  i) Methotrexate (20mg/week), sulfasalazine (2g/day) and hydroxychloroquine (400mg/day) for at least 3 months. (Hydroxychloroquine is based by weight up to 400mg per day.)

Maintenance/Renewal:

After 12 months of treatment, maintenance therapy is funded for patients with objective evidence of at least a 20 percent reduction in swollen joint count and a minimum of improvement in 2 swollen joints over the previous year.

For renewals beyond the second year, the patient must demonstrate objective evidence of preservation of treatment effect.

Therapy must be prescribed by a rheumatologist or a physician with expertise in rheumatology.

The recommended dosing regimen is 3mg/kg/dose at 0, 2 and 6 weeks followed by maintenance therapy of 3mg/kg/dose every 8 weeks up to a maximum of six maintenance doses per year.

For the treatment of ankylosing spondylitis (AS) in patients who have severe active disease confirmed by radiographic evidence (see notes below) with:

I.    Age of disease onset less than or equal to 50; AND

II.   Low back pain and stiffness for greater than 3 months that improves with exercise and not relieved by rest; AND

III.  Failure to respond to or documented intolerance to adequate trials of 2 non-steroidal anti-inflammatory drugs (NSAIDs) for at least 4 weeks each; AND

IV.   Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of greater than or equal to 4 for at least 4 weeks while on standard therapy.

Note: Radiographic evidence demonstrating the presence of "SI joint fusion" or "SI joint erosion" on x-ray or CT scan, or MRI demonstrating the presence of "inflammation" or "edema" of the SI joint.

Maintenance/Renewal:

After 12 months of treatment, maintenance therapy is funded for patients with objective evidence of at least a 50 percent reduction in BASDAI score or greater than or equal to 2 absolute point reduction in BASDAI score. For funding beyond the second year, the patient must demonstrate objective evidence of preservation of treatment effect.

Therapy must be prescribed by a rheumatologist or a physician with expertise in rheumatology. 

The recommended dosing regimen is 3 to 5mg/kg/dose at 0, 2 and 6 weeks followed by maintenance therapy of up to 5mg/kg/dose every 6 to 8 weeks.

For the treatment of psoriatic arthritis in patients who have severe active disease (greater than or equal to 5 swollen joints and radiographic evidence of psoriatic arthritis) despite: i) treatment with methotrexate (20mg/week) for at least 3 months; AND ii) one of leflunomide (20mg/day) or sulfasalazine (1g twice daily) for at least 3 months.

If the patient has documented contraindications or intolerances to methotrexate, then only one of leflunomide (20mg/day) or sulfasalazine (1g twice daily) for at least 3 months is required.

Maintenance/Renewal:

After 12 months of treatment, maintenance therapy is funded for patients with objective evidence of at least a 20 percent reduction in swollen joint count and a minimum of improvement in 2 swollen joints over the previous year. For funding beyond the second year, the patient must have objective evidence of preservation of treatment effect.

Therapy must be prescribed by a rheumatologist or a physician with expertise in rheumatology.

The recommended dosing regimen is 5mg/kg/dose at 0, 2 and 6 weeks followed by maintenance therapy of 5mg/kg/dose every 8 weeks.

For the treatment of severe* plaque psoriasis in patients 18 years of age or older who have experienced failure, intolerance, or have a contraindication to adequate trials of several standard therapies**.

Claims for the first 6 months must be written by a dermatologist.

Monitoring of patients is required to determine if continuation of therapy beyond 12 weeks is required.

Patients not responding adequately at 12 weeks should have treatment discontinued.

*Severe plaque psoriasis:

- Body Surface Area (BSA) involvement of at least 10 percent, or involvement of the face, hands, feet or genital regions, AND

- Psoriasis Area and Severity Index (PASI) score of at least 10 (not required if there is involvement of the face, hands, feet or genital regions), AND

- Dermatology Life Quality Index (DLQI) score of at least 10.

**Failure, intolerance or contraindication to adequate trials of standard therapies:

- 6-month trial of at least 3 topical agents including vitamin D analogues and steroids, AND

- 12-week trial of phototherapy (unless not accessible), AND

- 6-month trial of at least 2 systemic, oral agents used alone or in combination

- Methotrexate 15 to 30mg/week

- Acitretin (could have been used with phototherapy)

- Cyclosporine

Maintenance/Renewal:

After 3 months of therapy, patients who respond to therapy should have:

- At least a 50% reduction in PASI, AND

- at least a 50% reduction in BSA involvement, AND

- at least a 5-point reduction in DLQI score

The recommended dosing regimen is 5mg/kg/dose at 0, 2 and 6 weeks followed by maintenance therapy of 5mg/kg/dose every 8 weeks.

Ulcerative Colitis

For the treatment of moderate to severe ulcerative colitis in patients who meet the following criteria:

A. Mayo score greater than or equal to 6 with an endoscopic subscore* of at least 2 (or other validated disease activity score confirming moderate to severe disease); 

AND

B. Failed conventional treatment with a corticosteroid (prednisone 40-60mg/day [or equivalent]) for a minimum of 14 days (or intravenous corticosteroid for 1 week);

OR

Responded to/stabilized on conventional treatment with a corticosteroid, with or without an immunosuppressant (e.g., azathioprine, 6-mercaptopurine);

OR

Conventional treatment with a corticosteroid is contraindicated;

AND

C. Infliximab is being used to induce remission or as a steroid-sparing maintenance therapy.

*The endoscopy procedure must be done within the 12 months prior to initiation of treatment.

The recommended induction dosing regimen is 5mg/kg/dose at 0,2, and 6 weeks.

The recommended maintenance dosing regimen is 5mg/kg/dose every 8 weeks. (Note: higher doses may be considered in patients who have failed to respond to lower doses.)

Maintenance/Renewal:

Maintenance therapy is funded for patients who met the initiation criteria and have demonstrated a treatment response or are in remission. Examples of treatment response include clinically meaningful reductions in disease activity scores (e.g., Mayo score less than 6), along with improvements in endoscopic findings and reduction or discontinuation of corticosteroids.

Prescribers may wish to consider other funded alternatives for patients unable to discontinue corticosteroid therapy.

Exclusion criteria (initial and renewal coverage):

-Combination therapy with another biologic used to treat inflammatory bowel disease will not be funded.

Patients with mild ulcerative colitis (e.g., Mayo score less than 6) may be considered on a case-by-case basis through the Exceptional Access Program.

Luminal Crohn's disease

For the treatment of moderate to severe (luminal) Crohn's disease in patients who meet the following criteria:

A. Harvey Bradshaw Index (HBI) score greater than or equal to 7 (or other validated disease activity score confirming moderate to severe disease);

AND

B. Failed conventional treatment with a corticosteroid (prednisone 40-60mg/day [or equivalent]) for a minimum of 14 days (or intravenous corticosteroid for 1 week);

OR

Responded to/stabilized on conventional treatment with a corticosteroid, with or without an immunosuppressant (e.g., azathioprine, 6-mercaptopurine, methotrexate);

OR

Conventional treatment with a corticosteroid is contraindicated;

AND

C. Infliximab is being used to induce remission or as a steroid-sparing maintenance therapy.

The recommended induction dosing regimen is 5mg/kg/dose at 0, 2, and 6 weeks.

The recommended maintenance dosing regimen is 5mg/kg/dose every 8 weeks. (Note: higher doses up to 10mg/kg/dose may be considered in patients who have failed to respond to lower doses.)

Maintenance/Renewal:

Maintenance therapy is funded for patients who met the initiation criteria and have demonstrated a treatment response or are in remission. Examples of treatment response include clinically meaningful reductions in disease activity scores (e.g., HBI score decrease greater than or equal to 50% from pre-treatment measurement), along with improvements in endoscopic findings and reduction or discontinuation of corticosteroids.

Prescribers may wish to consider other funded alternatives for patients unable to discontinue corticosteroid therapy.

Exclusion criteria (initial and renewal coverage):

- Combination therapy with another biologic used to treat inflammatory bowel disease will not be funded.

Patients with mild Crohn's disease (e.g., HBI less than 7) may be considered on a case-by-case basis through the Exceptional Access Program.

Fistulising Crohn's disease

For the treatment of fistulising Crohn's disease in patients who meet the following criteria:

- Patient has actively draining perianal or enterocutaneous fistula(e) that have recurred OR persist despite a course of appropriate antibiotic therapy (e.g., ciprofloxacin and/or metronidazole)

The recommended induction dosing regimen is 5mg/kg/dose at 0, 2, and 6 weeks.

The recommended maintenance dosing regimen is 5mg/kg/dose every 8 weeks. (Note: higher doses up to 10mg/kg/dose may be considered in patients who have failed to respond to lower doses.)

Maintenance/Renewal:

Maintenance therapy is funded for patients who met the initiation criteria and achieve and maintain response to therapy (e.g., partial or complete resolution of fistulae and symptom improvement).

Exclusion criteria (initial and renewal coverage):

- Combination therapy with another biologic used to treat inflammatory bowel disease will not be funded.

Abatacept

• Brand(s): Orencia
• Dosage Form/Strength: 250 mg/15 mL vial (Note that the SC injection is not approved for this indication)

Infliximab - See formulary for funded biosimilars

• Brand(s): Avsola, Inflectra, Renflexis Biosimilars); Remicade (Originator)
• Dosage Form/Strength: 100 mg/vial

Rituximab

• Brand(s): Riximyo, Ruxience, and Truxima (biosimilar); Rituxan (biologic originator for those meeting biosimilar exemption)
• Dosage Form/Strength: 10 mg/mL intravenous injection

Originator biologics (e.g., Enbrel®, Humira®, Remicade®, and Rituxan®) with a provincially funded biosimilar are only considered for provincial funding in patients who are treatment experienced and stable on the reference biologic or those with existing EAP approvals. Prescribers should refer to the ODB formulary for biosimilars and their funded conditions.

It should be noted that after the date when a biosimilar becomes publicly funded for an approved indication, patients initiated on a originator biologic for this same provincially funded indication through support from a manufacturer’s patient support program, may be expected to be provided ongoing access of the reference biologic through the patient support program or to use a biosimilar upon meeting specified criteria. The Ministry will only consider funding of Originator biologics with a funded biosimilar version in those who are treatment experienced and stabilized on the product prior to transitioning to the ODB program or in patients with an existing EAP approval.

Refer to the Executive Officer Communications on the Ministry website for Frequently asked questions and notifications of funded biosimilars at http://www.health.gov.on.ca/en/pro/programs/drugs/opdp_eo/eo_communiq.aspx

Effective March 31, 2023, the ODB program will start transitioning coverage for Copaxone®, Enbrel®, Humalog®, Humira®, Lantus®, NovoRapid®, Remicade®, and Rituxan® to their biosimilar versions.

Effective December 29, 2023, coverage for these originator biologic drugs through the ODB program will not be available for patients and the ODB program will only provide coverage for the biosimilar version of these drugs for all ODB program recipients, with limited exemptions (see below). In general, for ODB program recipients who are already on these biologic drugs, there is up to a 9-month transition period (see the biosimilar switch policy described on page 6 of this document)

For the treatment of polyarticular-course juvenile idiopathic arthritis in patients meeting the following criteria:

1. Patient has active disease (a minimum of 3 (three) swollen joints and a total of 5 active joints); AND

2. Patient has had an inadequate response to a three-month course of methotrexate administered subcutaneously at a dosage of at least 15 mg/m² per week for at least 3 months. If the patient is unable to tolerate or has a contraindication to subcutaneous methotrexate the nature of the intolerance or contraindication must be described in detail.; AND

3. Patient has had an inadequate response to a three-month course of etanercept OR adalimumab OR tociluzumab. If the patient is unable to tolerate or has a contraindication to etanercept OR adalimumab OR tociluzumab, the nature of the intolerance or contraindication must be described in detail.

Duration of Approval: 1 Year

Renewals will be considered for patients with objective evidence of at least a 20% reduction in swollen joint count. For renewals beyond the second year, objective evidence of preservation of treatment effect should be provided. (i.e., the current joint count should be compared to the count prior to initiating treatment with the biologic agent)

Duration of Approval: 5 Year

Approved Dose:

• Abatacept refer to the Orencia product monograph for dosing information

• Infliximab dose up to 6mg/kg/dose at 0, 2 and 6 weeks followed by maintenance of up to 6mg/kg/dose every 8 weeks

EAP Drug Request Form:

Standard Form for EAP Drug Requests

Adalimumab – see Formulary for funded biosimilars

• Brand(s): Humira and formulary listed biosimilars
• Dosage Form/Strength: 40 mg/0.8mL prefilled syringe, 40 mg/0.8mL and 20 mg/0.2 mL prefilled pens for subcutaneous injection

Anakinra

• Brand(s): Kineret
• Dosage Form/Strength: 100 mg /0.67 mL subcutaneous injection

Certolizumab pegol

• Brand(s): Cimzia
• Dosage Form/Strength: 200 mg/mL prefilled syringe and autoinjector

Etanercept – see Formulary for funded biosimilars

• Brand(s): Enbrel
• Dosage Form/Strength: 25 mg and/or 50 mg prefilled syringe or pens for subcutaneous injection per formulary listed options

Golimumab

• Brand(s): Simponi
• Dosage Form/Strength: 50 mg/0.5 mL prefilled syringe and autoinjector

Infliximab – see Formulary for funded biosimilars

• Brand(s): Remicade
• Dosage Form/Strength: 100 mg/vial intravenous infusion

Originator biologics (e.g., Enbrel®, Humira®, Remicade®, and Rituxan®) with a provincially funded biosimilar are only considered for provincial funding in patients who are treatment experienced and stable on the reference biologic or those with existing EAP approvals. Prescribers should refer to the ODB formulary for biosimilars and their funded conditions.

It should be noted that after the date when a biosimilar becomes publicly funded for an approved indication, patients initiated on a originator biologic for this same provincially funded indication through support from a manufacturer’s patient support program, may be expected to be provided ongoing access of the reference biologic through the patient support program or to use a biosimilar upon meeting specified criteria. The Ministry will only consider funding of Originator biologics with a funded biosimilar version in those who are treatment experienced and stabilized on the product prior to transitioning to the ODB program or in patients with an existing EAP approval.

Refer to the Executive Officer Communications on the Ministry website for Frequently asked questions and notifications of funded biosimilars at http://www.health.gov.on.ca/en/pro/programs/drugs/opdp_eo/eo_communiq.aspx

Effective March 31, 2023, the ODB program will start transitioning coverage for Copaxone®, Enbrel®, Humalog®, Humira®, Lantus®, NovoRapid®, Remicade®, and Rituxan® to their biosimilar versions.

Effective December 29, 2023, coverage for these originator biologic drugs through the ODB program will not be available for patients and the ODB program will only provide coverage for the biosimilar version of these drugs for all ODB program recipients, with limited exemptions (see below). In general, for ODB program recipients who are already on these biologic drugs, there is up to a 9-month transition period (see the biosimilar switch policy described on page 6 of this document)

For the treatment of rheumatoid arthritis in patients who have:

1. Severe active disease (≥ 5 swollen joints and rheumatoid factor positive and/or, anti-CCP positive, and/or radiographic evidence of rheumatoid arthritis) despite the optimal use of various formulary disease-modifying anti-rheumatic drugs (DMARDs)*.

   *Optimal use of DMARDs include:

• Methotrexate (20 mg/week) for at least 3 months and leflunomide (20 mg/day) for at least 3 months in addition to an adequate trial (3 months) of at least one combination of DMARDs;

  OR

• Methotrexate (20 mg/week) for at least 3 months and leflunomide in combination with methotrexate for at least 3 months.

  Note: If the patient could not receive adequate trial(s) of methotrexate and/or leflunomide due to contraindication(s) or intolerance(s), the nature of contraindication(s) or intolerance(s) must be provided along with details of trials of other DMARDs or clear rationale why other DMARDs cannot be considered.

  OR

• Methotrexate (20mg/week), sulfasalazine (2 GM/day) and hydroxychloroquine (400mg/day)* for at least 3 months. If the patient could not receive an adequate trial of methotrexate, sulfasalazine and hydroxychloroquine due to intolerance, then the above DMARD trial criteria must be met.

  *Hydroxychloroquine is based by weight up to 400 mg per day

Duration of Approval: 1 Year

Renewal will be considered for patients with objective evidence of at least a 20% reduction in swollen joint count and a minimum of improvement in 2 swollen joints over the previous year. For renewals beyond the second year, objective evidence of preservation of treatment effect must be provided.

The planned dosing regimen for the requested biologic should be provided.

The recommended doses for the treatment of rheumatoid arthritis are as follows:

• Adalimumab 40mg every two weeks

• Anakinra 100mg per day

• Certolizumab pegol 400mg at 0, 2 and 4 weeks followed by maintenance therapy of 200 mg every 2 weeks. For maintenance dosing, 400mg every 4 weeks may be considered

• Etanercept 25mg twice weekly or 50mg once weekly

• Golimumab 50mg once a month

• Infliximab 3mg/kg/dose at 0, 2 and 6 weeks followed by maintenance therapy of 3mg/kg/dose every 8 weeks up to a maximum of six maintenance doses per year

Duration of Approval:
- First Renewal: 1 Year
- Subsequent Renewals: 5 Years

EAP Drug Request Form:

Standard Form for EAP Drug Requests

Adalimumab – See Formulary for funded biosimilars

• Brand(s): Humira and formulary listed biosimilars
• Dosage Form/Strength: 40mg/0.8mL prefilled syringe, 40mg/0.8mL and 20 mg/0.2 mL prefilled pens for subcutaneous injection

Certolizumab

• Brand(s): Cimzia
• Dosage Form/Strength: 200 mg/mL prefilled syringe and autoinjector

Etanercept – See Formulary for funded biosimilars

• Brand(s): Enbrel and formulary listed biosimilars
• Dosage Form/Strength: 25mg/vial and 50mg prefilled syringe for subcutaneous injection

Golimumab

• Brand(s): Simponi
• Dosage Form/Strength: 50 mg/0.5 ml prefilled syringe and autoinjector

Infliximab- See Formulary for funded biosimilars

• Brand(s): Remicade and formulary listed biosimilars
• Dosage Form/Strength: 100mg/10mL intravenous infusion

Secukinumab

• Brand(s): Cosentyx
• Dosage Form/Strength: 150 mg/mL prefilled syringe and 150 mg/mL prefilled pen

Infliximab - See formulary for funded biosimilars

• Brand(s): Avsola, Inflectra, Renflexis (Biosimilars); Remicade (Originator)
• Dosage Form/Strength: 100mg/vial Injection for Infusion

Adalimumab – See Formulary for funded biosimilars

• Brand(s): Humira and formulary listed biosimilars
• Dosage Form/Strength: 40 mg/0.8 mL prefilled syringe, 40mg/0.8mL and 20 mg/0.2 mL prefilled pens for subcutaneous injection

Infliximab – See formulary for funded biosimilars

• Brand(s): Remicade and formulary listed biosimilars
• Dosage Form/Strength: 100 mg/Vial Injection for infusion

Adalimumab – see Formulary for funded biosimilars

• Brand(s): Humira and formulary listed biosimilars
• Dosage Form/Strength: 40mg/0.8mL prefilled syringe, 40mg/0.8mL and 20 mg/0.2 mL prefilled pens for subcutaneous injection

Etanercept – see Formulary for funded biosimilars

• Brand(s): Enbrel and formulary listed biosimilars
• Dosage Form/Strength: 25mg/vial, 50 mg prefilled syringe for subcutaneous injection

Infliximab – see Formulary for funded biosimilars

• Brand(s): Remicade and formulary listed biosimilars
• Dosage Form/Strength: 100 mg/vial

Updated: March 29, 2021