Rheumatoid Arthritis (RA) is a chronic disease characterized by a distinctive pattern of bone and joint destruction. Incidence peaks in individuals aged around 70 years of age, but all ages can develop the disease. First line treatment for RA is through disease modifying antirheumatic drugs (DMARDs). In addition, a short course of low-dose oral corticosteroids is recommended. As corticosteroid (CS) therapy is associated with a variety of adverse outcomes, this study sets out to examine the risk of several important adverse outcomes in a population of RA patients. We will further assess healthcare resource utilisation associated with corticosteroid use in RA patients, as well as the incidence of all-cause hospitalisation in RA patients compared to non-RA patients.
Rheumatoid Arthritis (RA) is a chronic, erosive inflammatory arthritis characterized by a distinctive pattern of bone and joint destruction. It can follow at least three potential disease courses; monocyclic, polycyclic and progressive. Symptoms include tender and swollen joints, stiffness, nodules, fatigue, fever and weight loss. As the disease progresses joint deformation may occur. Juvenile rheumatoid arthritis (JRA) occurs in children under 16 years of age causing joint pain, swelling and stiffness. Symptoms may last a few months, but for some they can be long-term.
Incidence for RA varies across regions, with incidence rates ranging from 20-50 cases per 100,000 population in North America and Northern Europe, and 9 to 24 cases in Southern Europe. In the UK, it is estimated that approximately 1.5 men and 3.6 women per 10,000 people develop RA per year. Cases of JRA are much rarer, with an incidence rate of 1 per 10,000 children per year in the UK. The incidence of RA peaks around 70 years of age, but all ages can develop the disease. The JRA incidence is greater in females compared to males, with an early disease onset reported more common in girls than boys. The etiology of JRA and RA is not completely understood, but alongside immunologic and hormonal factors it is thought that genetic, environmental, lifestyle factors and infectious agents are involved.
Disease activity remission and prevention of joint damage are the main goals of treatment. First line treatment for RA is through disease modifying antirheumatic drugs (DMARDs), which include methotrexate, hydroxychloroquine, sulfasalazine, and leflunomide. A combination of methotrexate with at least one other DMARD is recommended. In addition, a short course of low-dose oral corticosteroids, consisting of prednisolone or prednisone, is recommended in combination with DMARD therapy to provide short term relief of symptoms and to minimize radiologically documented joint damage. In some cases, intra-articular corticosteroid injections may also be required. Biological drugs may be required in patients who are non-responsive to or intolerant to traditional DMARD therapies. If all other treatment options have been exhausted, long-term treatment with corticosteroids may have to be administered. Flares in RA disease activity are common; these are generally managed through the increase of methotrexate doses and by short term treatment with corticosteroids. In some cases, steroid injections may be advised. In addition to the above treatment regimes, non-steroidal anti-inflammatory drugs are generally prescribed to reduce pain and to minimize inflammation; proton pump inhibitors are recommended in combination to reduce NSAID induced gastrointestinal toxicity. For JRA, NSAIDs may be sufficient to control symptoms if few joints are involved. If not, as with adult RA, DMARDS as well as biological drugs are generally used in JRA treatment, alongside corticosteroids during periods of disease flare.
It is well established that corticosteroid therapy is associated with a variety of adverse effects. These may include weight gain, osteoporosis, fractures, hypertension, diabetes, cataracts, and myopathy. In patients with RA an increased risk in the development of serious adverse effects with corticosteroids has been observed. However, studies specifically examine the relationship between corticosteroid exposure and the development of adverse effects such as diabetes and glaucoma in RA patients are rare, and those undertaken appear to be limited by specific sub-populations and small sample size. Despite extensive work on the association between corticosteroids and the risk of fractures and infection in RA patients, many studies examined a limited number of fracture sites or infection types, with few investigating the overall risk associated with corticosteroid exposure. Furthermore, a lack of accounting for residual confounding by RA severity/flares is apparent in many studies. As patients with high disease activity may be more likely receiving corticosteroids this may produce misleading results due to an inability to separate the effects of corticosteroid use from disease severity. The need for additional large-scale, population-based studies which attempt to account for disease severity, are required, examining the threshold at which corticosteroid related serious adverse effects occur. This is important not only to further add to the knowledge and understanding of the adverse effects associated with corticosteroids use in RA patients, but also to help maximise the benefits of their use whilst minimising patient risks.
The current proposal describes a study to examine the risk of developing serious adverse effects (SAEs) in RA patients, specifically examining the effect of prednisolone/prednisone use in RA patients on the development of adverse outcomes. In addition, healthcare resource utilisation in RA patients will be examined.
Christoph Meier - Chief Investigator - University of Basel
Jessica Claire Wilson - Corresponding Applicant - Queen's University Belfast
Alexandra Mills - Collaborator - BCDSP - Boston Collaborative Drug Surveillance Program
Attila Petho Schramm - Collaborator - F. Hoffmann - La Roche Ltd
Khaled Sarsour - Collaborator - Genentech, Inc.
Pavel Napalkov - Collaborator - Roche
Susan Jick - Collaborator - BCDSP - Boston Collaborative Drug Surveillance Program
HES Admitted Patient Care