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You are here: Home / Our Medicines / Actemra

Actemra

Actemra is an anti-IL6 receptor antibody for rheumatoid arthritis, systemic juvenile idiopathic arthritis, and polyarticular juvenile idiopathic arthritis.

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Please review the Data Sheet before prescribing.

Actemra is an anti-interleukin-6 (anti-IL-6) monoclonal antibody used to treat rheumatoid arthritis (RA), systemic juvenile idiopathic arthritis (sJIA), polyarticular juvenile idiopathic arthritis (pJIA) and giant cell arteritis (GCA).1

Actemra is a Prescription Medicine, available as:1

  • 162 mg/0.9 mL pre-filled syringe for subcutaneous (SC) injection
  • 80 mg/4 mL, 200 mg/10 mL and 400 mg/20 mL vials for intravenous (IV) infusion

For information on dosage and administration of Actemra, please refer to the Data Sheet on the Medsafe website here.1

Actemra is registered by Medsafe for the following indications:1

Rheumatoid Arthritis (IV infusion and SC injection)

Actemra is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients:

  • in combination with methotrexate (MTX) in those not previously treated with MTX.
  • in combination with MTX or other non-biological disease-modifying anti-rheumatic drugs (DMARDs) in case of either an inadequate response or intolerance to previous therapy with one or more DMARDs.
  • as monotherapy in case of intolerance to MTX or where continued treatment with MTX is inappropriate.

Actemra has been shown to inhibit the progression of joint damage in adults, as measured by X-ray, when given alone or in combination with MTX.

Systemic Juvenile Idiopathic Arthritis (IV infusion only) 1

Actemra is indicated for the treatment of active systemic juvenile idiopathic arthritis (sJIA) in patients 2 years of age and older, who have responded inadequately to previous therapy with NSAIDs and systemic corticosteroids. Actemra can be given alone or in combination with methotrexate (MTX).

Polyarticular Juvenile Idiopathic Arthritis (IV infusion only) 1

Actemra is indicated for the treatment of active polyarticular juvenile idiopathic arthritis (pJIA) in patients 2 years of age and older who have shown an inadequate response to MTX.

Giant Cell Arteritis (SC injection only).1

Actemra is indicated for the treatment of giant cell arteritis (GCA) in adult patients.

Actemra’s Mechanism of Action

IL-6 is a multi-functional cytokine, produced by a variety of cell types involved in local paracrine function as well as regulation of systemic physiological and pathological processes such as induction of immunoglobulin secretion, T-cell activation, induction of hepatic acute phase proteins and stimulation of haematopoiesis. IL-6 has been implicated in the pathogenesis of diseases including RA.

Actemra is a recombinant, humanised, monoclonal antibody of the immunoglobulin IgG1 subclass which binds to both soluble and membrane-bound human IL-6 receptors.

Actemra has been shown to inhibit sIL-6R and mIL-6R-mediated signalling and as a result it has been proven to be effective in the treatment of RA, sJIA, pJIA and GCA.1

For a short video explaining Actemra’s mode of action click the image below.

Actemra’s Funding Status

Actemra is listed on the Hospital Medicines List (HML) within the Pharmaceutical Schedule for the treatments of RA, sJIA, and pJIA . 2

The SC Formulation of Actemra is not funded by Pharmac for RA nor for GCA.

To download the full funding criteria, go to the 'Resources' section below.

References:

  1. Actemra® (tocilizumab) Data Sheet. Available here.
  2. PHARMAC online hospital medicines list. Available at http://www.pharmac.govt.nz/HMLOnline. Accessed 17 January 2017

Actemra for the treatment of Giant Cell Arteritis (GCA)

GiACTA

The GiACTA study evaluated the efficacy and safety of Actemra in adults with giant-cell arteritis1

CLICK HERE FOR THE CLINICAL PAPER





Actemra monotherapy for RA

AMBITION

The AMBITION study compared Actemra monotherapy versus methotrexate monotherapy in patients with moderate to severe RA for whom treatment with methotrexate or biological agents had not previously failed.1

Click here for the clinical paper

ADACTA

ADACTA was a head-to-head Phase IV study of Actemra monotherapy versus adalimumab monotherapy in RA patients who were intolerant to methotrexate or for whom continuation of methotrexate was deemed inappropriate.2

Click here for the clinical paper


ACT-RAY

The ACT-RAY study compared the efficacy and safety profile of Actemra-plus-methotrexate versus Actemra-plus-placebo in patients with persistent, active RA despite methotrexate therapy.3

Click here for the clinical paper

Actemra combination therapy for RA: DMARD inadequate responders

OPTION

The OPTION study evaluated the efficacy of Actemra together with MTX versus placebo plus MTX in patients with moderate to severe active RA who have an inadequate response to methotrexate.4

Click here for the clinical paper

TOWARD

The TOWARD study examined the efficacy and safety of Actemra versus placebo, both groups in combination with conventional DMARDS, in patients with moderate to severe active RA.5

Click here for the clinical paper

LITHE

The LITHE study investigated the efficacy of Actemra in combination with MTX versus placebo plus methotrexate in patients with active RA who had an inadequate response to DMARDs.6

Click here for the clinical paper


Actemra combination therapy for RA: anti-TNF inadequate responders

RADIATE

The RADIATE study examined the efficacy and safety of Actemra in patients with moderate to severe active RA who failed to respond or were intolerant to TNF inhibitors.7

Click here for the clinical paper


Systemic Juvenile Idiopathic Arthritis (sJIA)

TENDER

The TENDER study evaluated the efficacy and safety of Actemra in children with systemic JIA.8

Click here for the clinical paper

Polyarticular Juvenile Idiopathic Arthritis (pJIA)

CHERISH

This pivotal study investigated the safety and efficacy of Actemra in children with severe active oligoarticular- or polyarticular-onset pJIA intractable to MTX pulses.9

Click here for the clinical paper

Key Safety Information

For the full Actemra safety information, please refer to the Data Sheet available here.10

To assess the long-term safety of Actemra in RA, pooled data was analysed from the five clinical trials OPTION, TOWARD, RADIATE, AMBITION and LITHE and the two long-term extension studies, GROWTH95 and GROWTH96. A total of 4171 patients were included, with a mean treatment duration of 3.9 years and a total observation time of 16,205 patient-years.12

Rates of serious adverse events and serious infections were stable over time (see Figure below).12

Adapted from Genovese M et al, 201312

Contraindications, Warnings and Precautions

Infections

  • Actemra is contraindicated in patients with severe, active infections.
  • Serious, sometimes fatal, infections have been reported. See Data Sheet for full list.
  • Caution in patients with recurring or chronic infections or underlying conditions that predispose patient to infection.
  • If serious infection develops, interrupt treatment until infection controlled.
  • Consider Actemra’s effect on signs and symptoms, including CRP and neutrophils when considering infection.
  • Inform patients and parents/guardians of vigilance for signs and symptoms of infection.
  • Not recommended in HIV, antibody-positive HBV, prior HCV, and symptomatic EBV.
  • Viral reactivation of HBV has been reported.

Complications of diverticulitis

  • Diverticular perforation and complications of diverticulitis reported.
  • Caution in patients with history of diverticulitis and intestinal ulceration.
  • Evaluate symptoms of abdominal pain promptly to identify GI perforation early.

Tuberculosis

  • Screen for latent TB prior to initiating; if positive, treat with standard anti-mycobacterial therapy before starting Actemra.

Vaccinations

  • Do not give live or live-attenuated vaccines concurrently.
  • Immunise prior to treatment.

Hypersensitivity reactions and immunogenicity

  • Serious hypersensitivity reactions reported, including fatal anaphylaxis to IV Actemra.
  • Low rates of immunogenicity (<2%). Medically significant, severe hypersensitivity reactions reported leading to Actemra withdrawal.
  • Do not re-challenge if history of hypersensitivity.
  • Treatment for anaphylactic reactions should be available for immediate use.
  • If serious hypersensitivity or anaphylactic reaction occurs, stop Actemra immediately and permanently discontinue.

Active hepatic disease, hepatic impairment and hepatic transaminases

  • Elevations in hepatic transaminases and bilirubin.
  • Caution patients with active hepatic disease or impairment (AST/ALT > 1.5 x ULN).
  • Treatment not recommended if AST/ALT > 5 x ULN.
  • Monitor 4-8 weekly for first 6 months, thereafter 12 weekly in RA. For patients with pJIA and sJIA, monitor at second infusion and then according to GCP. See Data Sheet for dose modifications and treatment interruptions.

Haematological abnormalities

  • Initiate with caution in patients with low neutrophil count. Not recommended in patients with ANC < 0.5 x 109/L.
  • Decreases in neutrophils and platelets. In RA, monitor at 4 to 8 weeks after start of treatment and in pJIA/sJIA at second infusion, and thereafter according to GCP.
  • Neutropenia risk increased in patients previously treated with TNF antagonist.
  • Serious infections may be increased, although no association to date.

Lipid parameters

  • Increased total cholesterol, LDL, HDL and triglycerides.
  • In majority of patients, no increases in atherogenic indices.
  • Treat according to local guidelines for hyperlipidaemia.

Demyelinating disorders

  • Vigilance for symptoms of new-onset central demyelinating disorders.

Malignancy

  • Immunomodulatory agents may increase risk of malignancy.

Infusion reactions (IRs)

  • IRs observed during and within 24 hours of treatment.

Cardiovascular (CV) risk

  • Monitor CV risk factors (hypertension, hyperlipidaemia).

Combination with other biological therapies

  • Not recommended in combination with other biological therapies.

Sodium

  • IV formulation contains sodium; consider in patients on sodium controlled diets.

Macrophage activation syndrome (MAS)

  • sJIA patients may develop MAS. Actemra has not been studied during an episode of active MAS.

Interactions with other medicines

  • Actemra reverses chronic inflammation and therefore CYP450 expression.
  • Monitor medicines which are individually adjusted or have narrow therapeutic index and metabolised via CYP450 3A4, 1A2, 2C9 or 2C19 (e.g. theophylline, warfarin, phenytoin, cyclosporine). Dose adjustment may be needed.

Pregnancy: Category C

  • Avoid treatment during pregnancy unless potential benefit to mother outweighs potential risk to foetus.
  • Use effective contraception during treatment and for several months following treatment.

Adverse effects: See Data Sheet for full list. In RA, pJIA and sJIA patients, the most common AEs (≥ 5%) were URTI, nasopharyngitis, headache, hypertension, increased ALT and bronchitis.

Please contact the Roche team for further information on the efficacy and/or safety of our products.

References

  1. Jones G, Sebba A, Gu J, et al. Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis 2010;69:88-96
  2. Gabay C, Emery P, van Vollenhoven R, et al. Tocilizumab monotherapy versus adalimumab monotherapy for the treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial. Lancet 2013;381:1541-1550
  3. Dougados M, Kissel K, Sheeran T, et al. Adding tocilizumab or switching tocilizumab monotherapy in methotrexate inadequate responders: 24-week symptomatic and structural results of a 2-year randomized controlled strategy trial in rheumatoid arthritis (ACT-RAY). Ann Rheum Dis 2013;72:43-50
  4. Smolen JS, Beaulieu A, Rubbert-Roth A, et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet 2008;371:987-997
  5. Genovese MC, McKay JD, Evgeny NL, et al. Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs. Arthritis Rheum 2008;58(10):2968-2980
  6. Kremer JM, Blanco R, Brzosko M, et al. Tocilizumab inhibits structural joint damage in rheumatoid arthritis patients with inadequate responses to methotrexate. Arthritis Rheum 2011;63(3):609-621
  7. Emery P, Keystone E, Tony HP, et al. IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biological: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis 2008;67:1516-1523
  8. De Benedetti F, Brunner HI, Ruperto N, et al. Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. N Engl J Med 2012;367:2385-2395
  9. Imagawa T, Yokota S, Mori M, et al. Safety and efficacy of tocilizumab, an anti-IL-6-receptor monoclonal antibody, in patients with polyarticular-course juvenile idiopathic arthritis. Mod Rheumatol 2012;22:109–115
  10. Actemra® (tocilizumab) Data Sheet. Available here.
  11. Campbell L, Chen C, Bhagatet S, et al. Risk of adverse events including serious infections in rheumatoid arthritis patients treated with tocilizumab: a systematic literature review and meta-analysis of randomized controlled trials. Rheumatol 2011;50:552-562
  12. Genovese MC, Sebba A, Rubbert-Roth A, et al. Long-Term Safety of Tocilizumab in Patients with Rheumatoid Arthritis Following a Mean Treatment Duration of 3.9 Years. EULAR 2013. Poster FRI0256

Actemra Funding Criteria

Click on the image for a two-page summary of the Hospital Medicines List funding criteria for the use of Actemra in RA.


Click on the image for a two-page summary of the Hospital Medicines List funding criteria for the use of Actemra in sJIA or pJIA.


Actemra Infusion Guidelines

Click on the image to download the 16-page instruction booklet about how to infuse Actemra for the treatment of RA, sJIA or pJIA.

Actembra Booklet


Actemra RA Patient Booklet

Click on the image below to download a 12-page booklet for patients with RA who have been prescribed Actemra.

This booklet has been created to be a helpful source of information that will support patients throughout their treatment. It is not meant to substitute any guidance, advice or help provided by their doctor, nurse or pharmacist.

More information for patients on Actemra can be found in the Consumer Medicine Information (CMI) leaflet, available here.

Actembra Medicines info


Actemra JIA Patient Booklet

Click on the image below to download a 12-page booklet for patients with sJIA or pJIA who have been prescribed Actemra.

This booklet is intended as an educational resource for parents, guardians and families throughout their child's treatment. It is not meant to substitute any guidance, advice or help provided by their doctor, nurse or pharmacist.

More information for patients on Actemra can be found in the Consumer Medicine Information (CMI) leaflet, available here.

Actemra JIA