Clinical outcomes are measurable changes in health, function or quality of life that result from our care. Constant review of our clinical outcomes establishes standards against which to continuously improve all aspects of our practice.
About the Rheumatology Service
The Rheumatology department at Great Ormond Street Hospital (GOSH) is the largest paediatric rheumatology department in the UK. We are a pioneering centre for research into musculoskeletal conditions, autoimmunity, and autoinflammatory diseases.
We treat, in accordance with the national guidelines, patients with arthritis and other inflammatory conditions. We also have a special interest in the treatment of children's non-inflammatory rheumatology problems. We work closely with other specialties within the hospital including Infectious Diseases, Immunology, and Nephrology.
We are a multidisciplinary team of doctors, physiotherapists, occupational therapists, psychologists, podiatrists, nurse specialists and administrators who all work together to support our patients and their families.
Cryopyrin-Associated Periodic Syndrome (CAPS)
Cryopyrin-Associated Periodic Fever Syndrome (CAPS) is an autosomal dominant genetic inflammatory disorder caused by excessive production by the immune system of an inflammatory hormone (cytokine) called interleukin-1. There are three subtypes as follows: familial cold urticarial syndrome; Muckle-Wells syndrome; and the most severe form, chronic infantile neurological cutaneous and articular (CINCA) syndrome. Affected adult patients have a 50% chance of passing the condition on to their children. Thus, it is not uncommon to have many generations of a family affected by the disease. The diagnosis and treatment of this group of conditions has been revolutionised by the discovery that the disease is caused by a mutation in a gene called NLRP3. This led to the realisation that treatment could be offered since this mutation causes excessive production of interleukin-1. In the UK, excessive amounts of interleukin-1 can be blocked using either Anakinra (given by daily subcutaneous injection), or the more recently introduced interleukin-1 blocker called Canakinumab, which is given every 8 weeks by subcutaneous injection. A curious observation is that some patients have what appears to be very typical clinical features of CAPS, and respond well to treatment even though no genetic mutation in NLRP3 is detected using current conventional genetic tests available on the NHS. We now know that a significant proportion of these ‘mutation-negative patients’ do actually harbour NLRP3 mutations, affecting their white blood cells at a level too low to be detected by conventional genetic tests - but detectable using more sensitive genetic tests (next generation sequencing).
The CAPS clinic at GOSH was established in January 2011. Funding for this was secured from the National Specialist Commissioning Group (NSCG, NHS England) by Professor Phil Hawkins at the Royal Free Hospital. This means that between GOSH and the Royal Free, there is a truly lifelong clinical service that caters for children, young people and adults with this rare genetic condition. The Royal Free provides the routine genetic testing; and we offer patients access to our research programme that uses next generation sequencing genetic testing to detect low levels of NLRP3 mutation, as well as screening for other potentially important genetic mutations.
We offer treatment for CAPS from early in life: Canakinumab is now available from the age of 2 years; Anakinra is available for those younger than 2 years old. We have published preliminary experience of using this treatment in children. As of 1st April 2019, the service has treated 50 paediatric CAPS patients, with some patients now transitioned to adult services. Currently 33 paediatric patients receive care at GOSH, with 25 receiving their active treatment at GOSH and eight at other UK hospitals. GOSH specialists monitor eye involvement, hearing involvement, and neurological involvement - all important complications of CAPS in some patients. To make our system even more efficient and cost effective for the NHS, we are establishing a dedicated pharmacist to prepare exact paediatric doses of Canakinumab in advance for individual children. This saves the NHS many tens of thousands of pounds per annum since vials of expensive drug can be used more efficiently, and the patient journey through the clinic can be optimised.
CAPS clinical outcomes
When assessing the response to these treatments, we apply a clinical score: the CAPS disease activity score (CAPS DAS). A score of 3 or less out of 20 indicates minimal or no clinical disease activity; higher scores indicate active disease. In addition, we routinely measure an inflammatory marker in the blood called serum amyloid A (SAA). Levels less than 10 are normal; higher levels may indicate that the disease is not sufficiently under control, even if there are few or no clinical symptoms.
We thus report the important summary outcome measures for the CAPS clinic at GOSH for current patients on active treatment: percentage of patients with disease activity score of 3 or less; percentage of patients with serum amyloid A less than 10; percentage of patients with both disease activity score less than 3 and normal serum amyloid A levels.
Figures reported below exclude patients whose care is actively reviewed at GOSH but who currently receive their treatment at other hospitals in the UK (using agreed clinical guidelines).
1. CAPS Disease Activity Score
Before treatment, 4% of the patients had a CAPS DAS score of 3 or below. This means almost all patients had active disease. After treatment, 88% of patients were in clinical remission with a score of 3 or less.
Fig. 1 CAPS Disease Activity Score pre-treatment and on treatment, as at April 2019
2. Serum Amyloid A levels
Prior to treatment, 43% of patients had abnormally high levels of SAA, meaning that their disease was not under control. After treatment with IL-1 blockade, 80% of patients had achieved normal SAA levels, indicating that their disease and related symptoms were under control.
Fig. 2 Serum Amyloid A levels pre-treatment and on treatment, as at April 2019
3. CAPS Disease Activity Score and Serum Amyloid A levels
This graph shows that only 4% of patients had both normal CAPS DAS scores and SAA level pre-treatment. However, once on treatment, 80% of patients were normal on both their CAPS DAS scores and their SAA levels.
Fig. 3 CAPS Disease Activity Score and Serum Amyloid A levels pre-treatment and on treatment, as at April 2019
Our outcomes for the treatment of CAPS indicate clinical effectiveness in diagnosing and controlling the disease. We continue to research how to improve diagnosis and treatment for patients with this rare condition.
This information was published in August 2019, and will be updated in August 2021.
Russo, R. A. G., et al. Efficacy and safety of canakinumab therapy in paediatric patients with cryopyrin-associated periodic syndrome: a single-centre, real-world experience, Rheumatology, 2014, 53: 665–670, https://doi.org/10.1093/rheumatology/ket415