ID012-Canakinumab-Scope.Pdf

NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE

Commissioning Support Programme

Scope to inform clinical evidence review of: canakinumab for the treatment of periodic fever syndromes (TRAPS, HIDS/MKD and FMF)

NICE ID012 / NHS England Policy URN 1813

June 2018

Remit To support the development of an NHS England specialised commissioning clinical policy on canakinumab within its marketing authorisation for the treatment of the following periodic fever syndromes:  Tumour necrosis factor receptor associated periodic syndrome (TRAPS)  Hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD)  Familial Mediterranean fever (FMF). Company Novartis

Regulatory status Canakinumab has a UK marketing authorisation for the treatment of the and licensed following autoinflammatory periodic fever syndromes in adults, adolescents indications and children aged 2 years and older:  Tumour necrosis factor (TNF) receptor associated periodic syndrome (TRAPS)  Hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD)  Familial Mediterranean fever (FMF) and should be given in combination with colchicine, if appropriate.  Cryopyrin-associated periodic syndromes (CAPS) including: o Muckle-Wells syndrome (MWS), o Neonatal-onset multisystem inflammatory disease (NOMID) / chronic infantile neurological, cutaneous, articular syndrome (CINCA), o Severe forms of familial cold autoinflammatory syndrome (FCAS) / familial cold urticaria (FCU) presenting with signs and symptoms beyond cold-induced urticarial skin rash. Canakinumab is also licensed for the treatment of:  active Still's disease including adult-onset Still's disease (AOSD) and systemic juvenile idiopathic arthritis (SJIA) in people aged 2 years and older who have responded inadequately to previous therapy with non-steroidal anti-inflammatory drugs (NSAIDs) and systemic corticosteroids NICE ID012 / Policy URN 1813 1 NICE commissioning support scope for canakinumab for treating periodic fever syndromes © NICE 2018 All rights reserved. Subject to Notice of rights.

 adults with frequent gouty arthritis attacks (at least 3 attacks in the previous 12 months) in whom NSAIDs and colchicine are contraindicated, are not tolerated, or do not provide an adequate response, and in whom repeated courses of corticosteroids are not appropriate. Dosing information The recommended starting dose for the treatment of TRAPS, HIDS/MKD and FMF is 150 mg for people with body weight greater than 40 kg and 2 mg/kg for people with body weight between 7.5 kg and 40 kg. This is administered every 4 weeks as a single dose via subcutaneous injection. For further dosing details please see the Summary of Product Characteristics (SPC) for canakinumab. Population Adults, adolescents and children aged 2 years and older with the following autoinflammatory periodic fever syndromes:  TRAPS  HIDS/MKD  FMF in combination with colchicine, if appropriate. Please note NHS England directly commissions treatment with canakinumab for people with cryopyrin-associated periodic syndromes (CAPS) and therefore this population is not included in this scope. Intervention Canakinumab (Ilaris)

Comparator(s) For TRAPS, HIDS/MKD, or FMF:  Standard care without canakinumab  NSAIDS  corticosteroids  anakinra*  etanercept*  tocilizumab*

For HIDS/MKD only  allogeneic haematopoietic stem cell transplantation

For FMF only:  colchicine**

* not licensed for this indication ** only licensed for the treatment of children with FMF for prophylaxis of attacks and prevention of amyloidosis (see SPC: colchicine for more information) Outcomes Clinical efficacy  Percentage of patients achieving resolution of baseline symptom flare or absence of new flare  Percentage of patients with serologic remission (C-reactive protein (CRP) levels 10 mg/L or less)  Percentage of patients with normalized serum amyloid A (SAA) levels 10 mg/L or less)

 Reduction/control of symptoms associated with the condition  Symptom-free time  Prevention of long-term complications associated with the condition such as amyloidosis, kidney failure, steroid-induced damage  Growth and development in children  Autoinflammatory disease damage index (ADDI)  Reduction in polypharmacy associated with managing individual symptoms  Physician Global Assessment (PGA) score of less than 2  Number of days with fever

Adverse events  Overall number of adverse events  Number of severe adverse events  Discontinuations due to adverse events The following outcomes are included as standard and will be considered where evidence allows: survival; progression free survival; health related quality of life (including mobility; self-care; usual activities; anxiety/depression); replacement of more toxic treatment; dependency on care giver/supporting independence; safety (including adverse effects); and delivery of intervention. Background – a brief The 3 rare diseases TRAPS, HIDS/MKD and FMF are a group of summary of the autoinflammatory conditions, which, have been classified under a single disease, term of inherited periodic fever syndromes. Periodic fever syndromes are epidemiology, characterised by short recurring episodes of fever and localised proposed benefit of inflammation which are not explained by an infection and are due to treatment and activation of the immune system. Onset of symptoms usually begins in current treatment in childhood, however symptoms may be delayed until adolescence. Typical the NHS in England episodes are accompanied by inflammation and blood abnormalities which (no more than 400 include raised white blood cells, and very high C-reactive protein (CRP) words). levels. An episode can last days or weeks, and the inflammatory disease can be sustained chronically in people. Some people with the condition may then go for long periods without significant symptoms until a flare occurs.

TRAPS is an autosomal dominant syndrome (where genetic mutations are inherited from only one parent) and is caused by a mutation of the TNFRSF1A gene. It has been reported in many ethnic groups and affects about 1 person in a million in Europe (UCL: Centre for Amyloidosis and acute phase proteins). Treatment with high dose corticosteroids can ameliorate an acute attack, but this does not prevent further attacks from occurring.

HIDS/MKD, is an autosomal recessive syndrome caused by mutations in the mevalonate kinase (MVK) gene. The prevalence is unknown but the estimated incidence is at around 200 people (Orphanet: HIDS).

FMF is the most common hereditary periodic fever syndrome. It is an autosomal recessive syndrome (where genetic mutations are inherited from both parents) and is caused by mutations of the MEFW gene (which

encodes pyrin, a protein found in white blood cells). This causes the immune system to become disrupted. The number of people living with FMF has not been reported, however, it mainly affects people originating from the Mediterranean (including Armenia, the Middle East, and Turkey). The prevalence is reported to be 1 to 5 per 10,000 in the wider Mediterranean population and 1 in 200 to 1 in 1000 in non-Ashkenazi Jews, Turks, Armenians and Arabs (Orphanet: FMF).

First line treatments primarily use a range of anti-inflammatory and immune- suppressing medicines including high dose steroids and NSAIDs. These medicines can help to reduce symptoms in some people with periodic fever syndromes. However, they are not always effective and some may cause side effects, particularly high dose steroids. Repeated courses of some of these medicines, notably steroids, can cause other problems such as weight gain, skin and bone thinning and susceptibility to diabetes and infections.

Colchicine has shown to be effective in controlling febrile attacks and preventing secondary amyloidosis in the majority of people with FMF However, it has been associated with the significant side effects of diarrhoea and transient elevation of transaminases and the rare side effects of liver dysfunction, leukopenia, and neuromyopathy. People who do not respond to or are intolerant to colchicine have very few, if any, treatment options (European public assessment report [EPAR] for canakinumab).

Other treatment for TRAPS, HIDS/MKD and FMF include anakinra, etanercept, tocilizumab and allogeneic haematopoietic stem cell transplant.

Canakinumab has been studied in adults, adolescents and children 2 years and older with TRAPS, HIDS/MKD and FMF.