Clinical Pharmacology And Prescribing Biology Essay

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This case shows a 45 year old male patient with severe ankylosing spondylitis. Ankylosing spondylitis (AS) is a form of arthritis that occurs at the lower back of the body. It is a chronic inflammatory disease that affects the spine and also the sacroiliac joints, which can be located between the sacrum and iliac bones1. The sacrum bone is located right above the tailbone whereas the iliac bones are the bones that can be found on the either side of the upper buttocks. The term ankylosing is defined as the fusion of joints and spondylitis is the inflammation of the spinal bones, also known as the vertebrae2. This condition causes the tendons that are being attached to the bones and also the joints between the spinal bones to be inflamed3. When inflammation occurs, the body will produce new bones to repair the damage, which will eventually fuse together, causing the spine to have permanent damage such as losing spinal mobility and also the development of a "question mark posture" called neck hyperextension1,3. Ankylosing spondylitis does not just affect the spinal bones but it is also a systemic disease which will spread to other parts of body and joints such as neck, eyes, heart and lungs and sometimes the kidney. Around 70% of patients complained of having neck pain while 10-40% of patients suffered from AS will develop cardiovascular disease during the course of the disease3. During the later stage of the disease progression, up to 40% of patients with AS will develop uveitis, which is the inflammation of the eye that can lead to scarring and blurring of vision and even blindness if not treated carefully4.

The prevalence of AS is around 0.25%-1% in the general population1. So it is roughly estimated that around one in 200 men and one in 500 women in UK develop AS2. The mortality rate is significantly high; with patients having 1.5 to 4 times likelihood to die from this disease especially since AS may increase the risk of developing cardiovascular diseases5,6. AS usually affects young people and patients will present symptoms of the disease around the age of 30. Men are twice as more likely to develop AS than women and their symptoms are also more pronounced compared to women whereby some men will have structural changes such as a "bamboo spine" whereas women might not have such obvious symptoms3.

Symptoms of AS can be as mild as none which occurred in 10% of the patients during the early stages and can also be as severe as losing spinal mobility due to irreversible structural damage4. The common symptoms for AS patients are lower back pain that radiates to the hips with alternating buttock pain which is made worse by rest. Patients are often awake at night due to unbearable back pain and they also experience spinal morning stiffness for more than 30 minutes that can be relieved through exercise1,7. The other common symptoms would be fatigue, and certain patients developed enthesitis, whereby there's an inflammation at the insertion site of tendon or ligaments into the bone especially on the heels such as Archilles tendonitis and also inflammation of the finger known as "sausage digit"1. Other extra articular symptoms includes aortitis, ulcerative colitis and also acute anterior uveitis (AAU), as the prevalence rate of AS with AAU for antigen HLA-B27 positive is 0.4% in the population and 0.02% in HLA-B27 negative population8.

For a patient who suffers from a chronic condition such as ankylosing spondylitis, their life expectancy would be 1.5 times lower than normal people and their quality of life would be greatly affected by it as the onset of the disease occurs at an earlier stage of life6. This affects mostly the working class individuals. About one third of individuals with AS would quit their job prematurely due to fatigue, impaired physical functioning, and low self esteem. The reduction in labour force can seriously damage the economy9. AS also affects patients in a social context due to increased concern about their medical condition and lesser time spent for leisure. Besides, they had to attend for routine medical checkups which will reduce the time spent with their friends and family10. Besides, drugs to relieve inflammation such as NSAIDs create more pain for the patient because of it undesirable gastro-intestinal side effects11. AS also affects patients' quality of life because it causes pain and disables them to a different extend, with certain patients having to undergo surgeries to replace joints and hips or even spinal surgery for patients with severely deformed spine6.

Patients with suspected AS are commonly diagnosed based on physical examination, clinical features and radiology evidence. The Modified New York criteria 1984 for ankylosing spondylitis is the most widely used diagnostic tool for AS4. They must fit the clinical criteria of having more than 3 months of lower back pain and morning stiffness which can be relieved through exercising, a reduction of spinal mobility and also a restricted chest expansion. MRI scan is also useful to detect any structural changes to the spine and to detect if any inflammation is present1,3

Aetiology (Cause) of disease

The cause of the disease is still unknown. However, there was a strong association between AS and the human leukocyte antigen B27 (HLA-B27), which is said could trigger inflammatory response towards infectious agents. The association between HLA-B27 and AS is more common among the Caucasian population12. A study done by the University of Leeds showed that 90.2% of their AS patients with HLA-B27 positive gene had a significantly longer duration of disease compared to AS patients with HLA-B27 negative gene even though their age is similar8. Over 90% of Caucasian AS patient are positive for HLA-B27 antigen but only 6-8% of the general population that are HLA-B27 positive will develop AS. Therefore, the HLA-B27 antigen is only responsible for 20-50% of patients that developed AS and most people with HLA-B27 positive antigen still remains healthy and free from AS3,13. A recent study shows that AS is not only caused by one gene, but it's a polygenic disease. The other genetic markers that are also linked to AS includes interleukin-1 (IL-1) gene cluster, aminopeptidase regulator of TNFR1 shedding (ARTS1), and the IL-23 receptor gene (IL-23R)14. Despite having theories regarding environmental and genetic predisposition that leads to AS, there are still no concrete evidence to what causes this disease and what is the mode of action for it13.

Treatment options

Mode of action

Clinical Outcome (% of success rate)

Side Effects, Costs, Advantages and Disadvantages compared with other drugs

Clinical Evidence of efficacy (Journals)

Visual Analogue Score (VAS) Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), which links the relationship between disease activity and fatigue

BASFI index indicates how it affects the patient. (assessment of as pg 9)- to determine how pt respond to treatment and disease activity.

Drug of choice:

NSAID 2. DMARD(methotrexate) 3. TNF a receptor blockers (Disease management pdf)

Cytokine modulators: TNF-α receptors blocker

Etanercept-mode of action and and infliximab undergo RCT.



So far, there are no specific literature guidelines for treatment of Ankylosing spondylitis. However, the International Assessment in AS (ASAS) society and the European League

against Rheumatism (EULAR) came out with evidence based recommendations for treatment of AS that involves 3 main types of drug treatments. The first line drug treatment for AS would be the use of NSAIDs such as phenylbutazone to minimise inflammation and to relieve pain and stiffness. If the patient still couldn't tolerate the pain or they couldn't tolerate NSAIDs, adjuvant therapy with low dose corticosteroids, analgesics and muscle relaxant should be given. The second line treatment comprised of

However, no treatments are available for slowing disease

progression. TNF antagonists seem to have little or no effect

on structural progression within 2e4 years in AS, in contrast

to rheumatoid arthritis (pathophysiology of AS)

Disease management

Cost effectiveness of INFLIXIMAB in (AS Pg 9)