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Take a look at a selection of our recent media coverage:

Oral upadacitinib approved by NICE for active psoriatic arthritis

17th January 2022

Oral upadacitinib has been approved by NICE either alone or in combination with methotrexate for the treatment of active psoriatic arthritis

Oral upadacitinib has been recommended by the National Institute for Health and Care Excellence (NICE) for use in adults with active psoriatic arthritis whose disease has failed to respond sufficiently to a disease-modifying anti-rheumatic drugs (DMARDs) or who cannot tolerate them.

However, in its final appraisal document, NICE made two further stipulations for its use. Firstly, that patients should have peripheral arthritis with 3 or more tender joints and 3 or more swollen joints and secondly, been previously treated with two conventional DMARDs and at least one biological DMARD and where tumour necrosis factor-alpha inhibitors are contra-indicated but would have otherwise been considered.

Oral upadacitinib is a once-daily biological DMARD and a Janus kinase 1 inhibitor (JAK 1) which has several indications in addition to active psoriatic arthritis including rheumatoid arthritis, atopic dermatitis and ankylosing spondylitis.

The clinical need for a range of treatment options for those with psoriatic arthritis is because the disease can develop at any age, is lifelong and has a hugely negative impact on patient’s quality of life, including education, career, relationships and family life.

The clinical efficacy of oral upadacitinib is based on two Phase III trials. In the first, SELECT PSA 1, upadacitinib at doses of 15 and 30mg, was compared with placebo and adalimumab in patients with an inadequate response to non-biologic DMARDS. The primary outcome of the trials was American College of Rheumatology (ACR) 20 response, which is a composite measure defined as an improvement of 20% in both the number of tender joints and the number of swollen joints, and a 20% improvement in 3 of the following 5 criteria: patient global assessment, physician global assessment, functional ability measure, visual analogue pain scale and erythrocyte sedimentation rate or C-reactive protein. The study found that both upadacitinib doses were non-inferior to adalimumab for the primary endpoint but significantly better than placebo.

The second trial, SELECT PSA 2, was a placebo-controlled trial without an active comparator and included patients with a prior inadequate response or intolerance to at least one biologic DMARD. The study, which employed the same primary endpoint as SELECT PAS 1, concluded that oral upadacitinib 15mg and 30mg was more effective than placebo over 24 weeks in improving signs and symptoms of psoriatic arthritis.

Due to the lack of direct comparative evidence for oral upadacitinib with other biological DMARDS, the manufacturer, Abbvie, submitted to NICE a network meta-analysis which compared their drug with two groups of patient, those with and without previous treatment with a biological DMARD. The results of the analysis, showed that overall, upadacitinib had broadly equivalent results compared with the current therapeutic options for people with psoriatic arthritis who either had, or not not had a biological DMARD.

However, the final appraisal document did conclude that oral upadacitinib was not recommended for patients who had not been previously treated with a biological DMARD.


ME/CFS guidance from NICE seeks to improve awareness and understanding of condition

3rd November 2021

Updated NICE ME/CFS guidance is designed to facilitate a greater awareness of the condition to ensure that is can be diagnosed earlier.

An updated guideline from NICE on myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome, ME/CFS, seeks to provide a clinicians with a better understanding of the condition, including its identification and assessment, management, monitoring and review. The terms “ME” and “CFS”, although used interchangeably, relate to the persistence of the symptom complex described below (suspecting ME/CFS). Although precise figures are not available, NICE suggests that there are over 250,000 people in England and Wales with ME/CFS and that the condition affects 2.4 times as many women as men.

The updated NICE guideline is designed to replace the original ME/CFS guidance from 2007.

Suspecting ME/CFS

NICE accepts the absence of a specific diagnostic test for ME/CFS and instead indicates that healthcare professionals should rely upon a clinical diagnosis where the following symptoms have persisted for a minimum of 6 weeks in adults and 4 weeks in children.

  • Debilitating fatigue that is worsened by activity, is not caused by excessive cognitive, physical, emotional or social exertion, and is not significantly relieved by rest
  • Post-exertional malaise after activity in which the worsening of symptoms, is is often delayed in onset by hours or days, is disproportionate to the activity and has a prolonged recovery time that may last hours, days, weeks or longer.
  • Un-refreshing sleep or sleep disturbance that may last hours, days, weeks or longer and might include feeling exhausted, feeling flu-like and stiff when walking.
  • Cognitive difficulties which may include problems finding words or numbers, difficulty in speaking, slowed responsiveness, short-term memory problems, and difficulty concentrating or multitasking.

In addition to the above, NICE recommends that clinicians suspect ME/CFS where “a person’s ability to engage in occupational, educational, social or personal activities is significantly reduced from pre‑illness levels” and “symptoms are not explained by another condition.” The guidance adds that clinicians “diagnose ME/CFS in a child, young person or adult who has the [above] symptoms that have persisted for 3 months and are not explained by another condition.”

The updated guideline is extensive, covering areas such as assessment and support, the importance of multidisciplinary care, symptom management as well as the need for healthcare professional training. Perhaps one of the most important sections in the guideline is the recognition that previously, people with ME/CFS  “may have experienced prejudice and disbelief and could feel stigmatised by people (including family, friends, health and social care professionals, and teachers) who do not understand their illness.”

Management

With no cure currently available, the guideline focuses on supportive measures such as energy management, defined as a “self-management strategy that involves a person with ME/CFS managing their activities to stay within their energy limit, with support from a healthcare professional.” In addition, though NICE advises against the use of any medicines or supplements to cure ME/CFS, the is a recognition that “pharmacological interventions are however commonly used for symptomatic relief in people with ME/CFS, for example for pain and sleep, even though evidence from clinical trials in ME/CFS may be lacking.”

While cognitive behavioural therapy is mentioned, ‘the committee wanted to highlight that cognitive behavioural therapy (CBT) has sometimes been assumed to be a cure for ME/CFS. However, it should only be offered to support people who live with ME/CFS to manage their symptoms, improve their functioning and reduce the distress associated with having a chronic illness.”

In a summary of the potential value of the updated guideline, Baroness Finlay, Consultant in Palliative Medicine, Clinical Lead for Palliative Care for Wales, and vice-chair of the guideline committee, suggested that “those with ME/CFS need to be listened to, understood and supported to adapt their lives.” Adding how “the committee members involved in this guideline have worked particularly hard to ensure care becomes more empathetic and focused on the individual’s needs.”

Finally, commenting in a post for the ME Association, Dr Charles Shepherd, who was a member of the guideline committee, said that the updated guideline “should be widely welcomed by people with ME,” adding that “the next challenge involves educating and training all health professionals on how to diagnose and manage ME and setting up a full network of hospital-based referral services where GPs can refer for further help.”

Citation

NICE. Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management. NICE guideline [NG206]

Crizanlizumab approved by NICE for preventing sickle cell crises

14th October 2021

NICE has approved crizanlizumab for sickle cell crises in patients with sickle cell disease but only as part of a managed access agreement.

NICE has given the green light to crizanlizumab for the management of sickle cell crises in people with sickle cell disease. The term sickle cell disease describes a group of inherited red blood cell disorders that affect haemoglobin and which, according to the World Health Organization, approximately 5% of the world’s population carries trait genes for such disorders. Sickle cell disease affects around 1 in 500 African American children and 1 in 36,000 Hispanic American children and is characterised by a change in the shape of red blood cells which become more ‘sickle-like”, reducing their flexibility of the cells. These sickle-like red blood cells can lead to recurrent and unpredictable blockage of small blood vessels producing ischaemic pain, referred to as vaso-occlusion (VOC) or sickle cell crises. In addition, activated and adherent leukocytes are the likely drivers of VOC in collecting venules and this process appears to be initiated by a transmembrane protein, P-selectin. Studies have shown that blockage of P-selectin appears to improve blood flow and thus reduce the risk of VOC and sickle cell–related pain crises.

Clinical efficacy

The monoclonal antibody crizanlizumab binds to P-selectin blocking its action. The approval by NICE was based on data from the SUSTAIN trial. This double-blind, randomised, placebo-controlled, Phase II trial, assigned 198 patients to either a low-dose crizanlizumab (2.5 mg per kilogram of body weight), a high-dose crizanlizumab (5.0 mg per kilogram), or placebo and which were administered intravenously 14 times over a period of 52 weeks. The primary outcome was the annual rate of sickle cell–related pain crises with high-dose crizanlizumab versus placebo. For the study, this was defined as acute episodes of pain caused by a VOC that resulted in a visit to a medical facility and treatment with pain relief medication. The results showed that the median rate of crises per year was 1.63 with high-dose crizanlizumab versus 2.98 with placebo (p = 0.01). In addition, the median time to the first crisis was significantly longer with high-dose crizanlizumab than with placebo (4.07 vs. 1.38 months, p = 0.001),as was the median time to the second crisis (10.32 vs. 5.09 months, p=0.02). In addition, the overall incidence of serious adverse event was comparable across the three arms.

NICE recognised that a limitation of the trial was the absence of longer term data on crizanlizumab such as mortality or among those who did not seek medical advice on VOCs. There was also no data on the prolonged treatment benefit and what happens when patients stop taking crizanlizumab.

While the appraisal document concluded that “Crizanlizumab is not recommended for routine use in the NHS“, the drug could be used where specific criteria are met. Thus, guidance notes that “crizanlizumab is recommended as an option for preventing recurrent sickle cell crises (vaso-occlusive crises) in people aged 16 or over with sickle cell disease only if the conditions in the managed access agreement are followed.

Source. NICE 2021