Opinion 23 July 2014

Transcription

1 The legally binding text is the original French version TRANSPARENCY COMMITTEE Opinion 23 July 2014 IMUREL 50 mg, film-coated tablet (B/100) (CIP: ) IMUREL 25 mg, film-coated tablet (B/50) (CIP: ) Applicant: H.A.C PHARMA INN ATC Code (2013) Reason for the review List concerned Indication concerned Azathioprine L04AX01 (immunosuppressant) Renewal of inclusion in rheumatoid arthritis National Health Insurance (French Social Security Code L ) "Severe rheumatoid arthritis" HAS - Medical, Economic and Public Health Assessment Division 1/5

2 01 ADMINISTRATIVE AND REGULATORY INFORMATION Marketing Authorisation (national procedure) Prescribing and dispensing conditions/special status Date initiated: 22 April 2004 List I ATC Classification 2013 L L04 L04A L04AX L04AX01 Antineoplastic and immunomodulating agents Immunosuppressants Immunosuppressants Other immunosuppressants azathioprine 02 BACKGROUND In the renewal of inclusion opinion for this proprietary medicinal product on 3 April 2013, the Committee was in favour of retaining a substantial AB for all the MA indications except for rheumatoid arthritis for which the AB was undergoing re-assessment. 03 CHARACTERISTICS OF THE MEDICINAL PRODUCT 03.1 Therapeutic indications Indications already assessed in April 2013: "Organ transplantation: prophylaxis of transplant rejection in combination with corticosteroids or other immunosuppressive agents. Autoimmune disease: treatment of systemic lupus erythematosus, autoimmune hepatitis (except for viral diseases), idiopathic thrombocytopaenic purpura, autoimmune haemolytic anaemia, dermatomyositis, polymoyositis, systemic vasculitis (except for viral diseases), pemphigus, Crohn's disease and ulcerative colitis. Imurel is indicated in the severe forms of these diseases, in patients intolerant to corticosteroids or corticosteroid-dependent or whose therapeutic response is insufficient despite high doses of corticosteroids." Indication forming the subject of this assessment: "Severe rheumatoid arthritis." HAS - Medical, Economic and Public Health Assessment Division 2/5

3 03.2 Dosage See SPC 04 ANALYSIS OF NEW AVAILABLE DATA 04.1 Efficacy The applicant has not provided any new clinical efficacy data for azathioprine in the treatment of rheumatoid arthritis. The literature search carried out by the documentation department of HAS did not identify clinical data with acceptable methodology published since the last Committee opinion and enabling the efficacy of azathioprine in the treatment of rheumatoid arthritis to be assessed Safety/Adverse effects No new safety data is available since the last assessment in The commonest adverse effects were haematological and gastrointestinal in nature Usage/prescription data According to IMS data (moving annual total winter 2013), I86,630 prescriptions were issued for IMUREL 25 and 50 mg. The small number of prescriptions is insufficient to allow reliable analysis of the data. There is no specific usage data for this proprietary medicinal product in rheumatoid arthritis (RA). According to the GERS [Group for the Development and Implementation of Statistics] pharmacy sales data, 316,060 boxes of IMUREL were sold between April 2012 and March 2013 and 273, 577 boxes between April 2013 and March Therapeutic strategy The current treatment of rheumatoid arthritis involves the prescription of a fast-acting anti-inflammatory (NSAID, corticosteroid) and a disease modifying drug to induce remission (clinical and laboratory parameters). Methotrexate is the standard reference disease modifying drug for rheumatoid arthritis. If there is inadequate response or contraindication to methotrexate, one of the following can be used depending on the presentation of the disease (clinical and laboratory parameters) and the pathophysiological context of the patient: - another disease modifying antirheumatic drug (DMARD) as monotherapy or; - a combination of DMARDs or; - an anti-tnf; - a biological therapy. The therapeutic use of azathioprine: HAS - Medical, Economic and Public Health Assessment Division 3/5

4 Azathioprine was not included in the latest update of the American College of Rheumatology (ACR) recommendations 1 in 2012 due to the rarity of its use and the absence of new data. In the previous version of the EULAR recommendations from 2010, 2 azathioprine could be used in exceptional circumstances (severe refractory RA or contraindication to biological agents or conventional DMARDs). This statement was removed (unanimously) from the updated version of the recommendations from In the rationale, this removal was justified by the existence of numerous effective biological and synthetic DMARDs and the unconvincing benefit/risk ratio in particular regarding the available treatments. Its use as first-line treatment should be rare and reserved for exceptional situations. According to the French Society of Rheumatology, "Imurel (azathioprine) should, in our view, be preserved because it is a powerful immunosuppressant which is particularly indicated in forms with systemic extra-articular manifestations. ". Given these factors, the Transparency Committee considers that azathioprine (IMUREL) retains a role in the therapeutic strategy for rheumatoid arthritis in particular in forms with systemic extra-articular manifestations. 05 TRANSPARENCY COMMITTEE CONCLUSIONS In view of all the above information, and following the debate and vote, the Committee considers that the conclusions of its previous opinion on 1 February 2006 relating to the RA indication have changed as follows: 05.1 Actual benefit Rheumatoid arthritis is a serious and debilitating chronic disease. IMUREL is intended as symptomatic treatment. Its efficacy/adverse effects ratio remains high. There are numerous treatment alternatives (synthetic and biological DMARDs). Azathioprine retains a role in the therapeutic strategy for rheumatoid arthritis in particular in forms with systemic extra-articular manifestations. Taking account of these points, the Committee considers that the actual benefit of IMUREL remains substantial in the "Treatment of severe rheumatoid arthritis" indication. 1 Singh et al Update of the 2008 American College of Rheumatology Recommendations for the Use of Disease- Modifying Antirheumatic Drugs and Biologic Agents in the Treatment of Rheumatoid Arthritis. Arthritis Care & Research 2012; 4: Smolen JS et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis 2010; 69: Smolen et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis 2014; 73: HAS - Medical, Economic and Public Health Assessment Division 4/5

5 05.2 Transparency Committee recommendations: The Committee recommends continued inclusion on the list of medicines refundable by National Health Insurance in the indication "severe rheumatoid arthritis". Proposed reimbursement rate: 65% Packaging Appropriate for the prescribing conditions according to the indication, dosage and treatment duration. HAS - Medical, Economic and Public Health Assessment Division 5/5