Arthritis Treatment Today
Starfish Slime Could Hold Key To New Treatment For Asthma, Arthritis
A non-stick slime made by starfish may lead to new treatments for asthma, arthritis, hay fever and other inflammatory conditions, say marine biologists in Scotland.
The scientists, from the Scottish Association for Marine Science (SAMS) in Oban, Argyll, have been studying the slime produced by the spiny starfish, Marthasterias glacialis, commonly found in the waters around Scotland and other parts of the British Isles, and say it could be vital for treating human infections.
Lead researcher Dr Charlie Bavington, founder and managing director of Glycomar, a marine biotechnology company based at SAMS, has been talking to the media about their work.
In an interview with the BBC aired on Thursday 9 December, he demonstrated how the starfish produced the slime: he took a starfish with a span of about 30 cm or 12 in out of a tank, held it, after a few seconds the slime began visibly to ooze from the creature’s spiny body.
The slime is a defence mechanism and also prevents debris from sticking to the starfish.
Bavington said the compound they were interested in was only part of the starfish’s “goo”; he showed BBC reporter Rebecca Morelle the purified compound, which looks like a white powder, and explained that they are planning to work with chemists to produce a man-made version.
They are hoping that the compound can do for blood vessels what it does for the starfish: stop things sticking to them.
Inflammatory conditions like asthma and arthritis are what happens when the body’s natural immune response to infection overreacts and white blood cells stick to and build up on the inside walls of blood vessels, damaging tissue.
Starfish are continually bathed in micro-organisms, bacteria, larvae, and viruses looking to set up camp on their spiny skin. But the slime that they secrete protects them from this continual onslaught by making their skin too slippery:
“… starfish are better than Teflon: they have a very efficient anti-fouling surface that prevents things from sticking,” said Bavington, according to a report in The Scotsman.
He said they want to see if the compounds they have isolated from the starfish slime could be developed into a drug that coats blood vessels to create the same effect and allow white blood cells to flow through without sticking to the sides.
“In humans cells stick from a flowing medium to a blood vessel wall, so we thought we could learn something from how starfish prevent this so we could find a way to prevent it in humans,” explained Bavington.
Clive Page, professor of pharmacology at King’s College London, is working with Bavington on this. He said discovering this substance in the starfish slime has dramatically shortened the usual timescale for developing a new treatment:
“The starfish have effectively done a lot of the hard work for us,” said Page, explaining that normally scientists have to screen hundreds of compounds before they find such a lead.
The starfish has had “billions of years in evolution to come up with molecules that do specific things,” he added.
The field of research that this kind of discovery belongs to is called glycobiology, a branch of biology that studies the structure, biosynthesis and function of sugar chains or saccharides, for which there is increasing interest because of the important role they play in cells.
Saccharides exist on cell surfaces, they mediate interaction between cells, and also between cells and the extracellular matrix and effector molecules.
Studies in this field are opening up possibilities for the discovery of new drugs made from saccharides or other molecules that target the biosynthesis and function of saccharides.
Managing inflammatory arthritis treatment for adults and children
Dr David Kane provides an update from the Irish Society for Rheumatology Annual Scientific Meeting, where delegates heard about advances in biological therapy and other care developments
The Irish Society for Rheumatology Winter Meeting was held at Killiney Castle on September 23-24 last. The theme of the meeting was ‘The Management of Inflammatory Arthritis in Adults and Children’. The meeting highlighted the major advances that have been made in the care of adults and children with inflammatory arthritis, particularly as a result of novel developments in biological therapy.
Importance of early treatment
Rheumatoid arthritis (RA) is estimated to affect 45,000 people in Ireland, with 2,250 new cases diagnosed each year. Some 75 per cent of these patients are of working age; 30 per cent of patients stop work within one year due to the effects of rheumatoid arthritis, with this increasing to 50 per cent at three years.
Dr Patrick Kiely of St George’s Hospital in London outlined the new paradigm of early, aggressive therapy in RA. Two pivotal studies published by Lard and Nell confirmed that there is an early window of opportunity to treat patients within the first three months of symptoms.
These patients should be commenced at the earliest opportunity on immunomodulatory therapy (disease modifying anti-rheumatic drugs) and/or steroids to obtain control of joint inflammation.
The benefits of early control of joint inflammation in preventing joint damage will persist for many years. However, in patients who have a delay in obtaining treatment for rheumatoid arthritis, there is clear evidence that they will have worse outcomes in terms of function, disability and radiological damage. There are three factors in the delay in obtaining treatment for rheumatoid arthritis.
In the early rheumatoid arthritis network in the United Kingdom, patients waited an average of four months before they sought a GP opinion for their joint pains. There was a second delay from the initial consultation with their GP before a referral to a rheumatologist was made. There was a third delay from referral to achieving the appointment with a rheumatologist.
Clearly, if strategies can be implemented to make patients aware to consult their GPs earlier, and if GPs can access the early arthritis referral pathways present in most Irish hospitals, then the possibility of treating people within the first three months of symptoms could be attainable. Most Irish hospitals now have early inflammatory arthritis referral criteria and designated rapid-access clinics or appointments.
The Fin-RACo study showed the treatment of RA within the first four months of diagnosis led to remission of 40 per cent, but treatment after four months led to remission of just 10 per cent. With remission, the new target of rheumatoid arthritis therapy, the consensus was that more work must be focused not just on earlier rheumatology appointments, but also on patient education.
The choice of treatment is also critical. Immunomodulatory treatment with disease-modifying, anti-rheumatic drugs should be started immediately on making the diagnosis of rheumatoid arthritis.
EULAR guidelines suggest the use of methotrexate, while recent NICE guidelines recommend a combination of methotrexate and sulfasalazine or another DMARDs.
Both EULAR and NICE guidelines recommend initial use of corticosteroids, either oral or intramuscular, to obtain rapid symptom control and to maintain patients at their usual level of social function.
Treat to target: remission
In addition to early treatment with immunomodulatory drugs, there is clear evidence that patients should be seen very frequently at the early stages of the disease and treated according to standardised protocols to obtain remission of joint symptoms. This requires practice change, whereby formal disease activity scores are recorded in patients at each visit, with therapy escalated until the disease activity score is less than 2.6 in early disease and 3.2 in established disease.
The optimal frequency in the TICORA study was one-monthly review of patients until they had obtained remission. Recent data from the RAISE study in Ireland suggest that most patients get an appointment on average of every six months, probably due to issues of capacity within the current system. The consensus was that any service reconfiguration in the future must accommodate frequent visits for patients with new or unstable rheumatoid arthritis until therapeutic target has been obtained.
The gains highlighted were clear, with a change from previous remission rates of approximately 10 per cent to a potential remission rate of 70 per cent using these. Dr Andrew Oster of Addenbrooke’s Hospital, Cambridge, reviewed the data on anti-TNF therapy. There are now five licensed anti-TNF therapies: adalimumab, etanercept, infliximab, golimumab and certolizumab.
All have proven efficacy in not just rheumatoid arthritis but also in psoriatic arthritis, ankylosing spondylitis and other inflammatory conditions. Dr Oster reviewed data from the ATTRACT, PREMIER and ARMADA studies, all of which demonstrate superiority to traditional disease-modifying, anti-rheumatic drugs. The Quinn study also suggests that the earlier these are introduced, the greater the potential to induce remission in patients with rheumatoid arthritis. Further data from the Irish RAISE study demonstrated the beneficial effects of these drugs in Irish patients.
In addition to the anti-TNF therapies, rheumatologists have the option to use anti-IL6 therapy (tocilizumab), anti-B cell therapy (rituximab) and anti-T cell therapy (abatacept).
Dr Oster reviewed the data from the REFLEX, ATTAIN and RADIATE studies demonstrating that all of these agents were effective when used in rheumatoid arthritis, with equivalent efficacies. Selection of optimal therapy for the patient depends on specific features of their disease activity and co-morbidities. There has been a revolutionary change in the management of RA now that eight novel, extremely efficacious biologic agents exist.
Managing co-morbidity and preventing premature mortality
Rheumatoid arthritis causes inflammation and damage of the joints. Most doctors, however, are unaware that most patients with RA will have a reduced life expectancy if the disease is inadequately controlled. It is expected that with the newer therapeutic approaches that the standard of treatment will improve and the frequency of co-morbidities of osteoporosis and coronary disease will diminish. At present, however, established rheumatoid arthritis patients must be viewed as being at significantly increased risk of coronary artery disease and osteoporotic fractures.
Advances in osteoporosis therapy
Prof Eugene McCloskey of the University of Sheffield reviewed the treatment of rheumatoid arthritis-related osteoporosis fractures. It is essential that doctors now recognised that patients with rheumatoid arthritis have an increased risk for osteoporotic fractures. The FRAX score has been developed for clinical diagnosis of osteoporosis within a primary care setting. It is available from www.shef.ac.uk/frax. By entering clinical data, the 10-year risk of all fractures and the 10-year risk of hip fracture can be calculated, allowing a decision on osteoporosis treatment.
Rheumatoid arthritis is an independent risk in the FRAX model, highlighting the strong association between rheumatoid arthritis and osteoporotic fractures.
Treatment for rheumatoid
arthritis-related osteoporosis
1. Antiresorptive: Oestrogen/SERMS; Bisphosphonate; Calcitonin
2. Calcium/vitamin D/calcitriol
3. RANK ligand targeted therapy
4. Anabolic therapy: Parathyroid hormone
5. Novel action: Strontium ranelate
Prof McCloskey outlined all of the available therapies for osteoporosis, particularly in the setting of rheumatoid arthritis. Currently, bisphosphonates, calcium and vitamin D are the mainstay of therapy. However, he presented data on a novel agent denosumab, which acts by inhibiting osteoclast formation.
Data in the FREEDOM trial demonstrated that three years of denosumab therapy produced a reduced risk of vertebral fracture (68 per cent), non-vertebral fracture (20 per cent) and hip fracture (40 per cent). The therapy is administered by two six-monthly subcutaneous injections, which were felt to improve patients’ compliance.
Added benefits may exist in rheumatoid arthritis where inhibition of osteoclast function has been shown to reduce the development of bone erosion, a key feature of rheumatoid joint damage.
Managing cardiovascular disease
Dr Vincent Maher of the Adelaide and Meath Hospital, Dublin, reviewed the increased risk of coronary heart disease and sudden death that exists in rheumatoid arthritis. Patients with rheumatoid arthritis have had a threefold increase in the incidence of acute myocardial infarction and a twofold increase in the incidence of sudden death. This appears to be related to therapy in the pre-biologic age and there is much hope from initial studies that more effective biological therapy may reduce the risk of coronary artery disease. This remains to be proven.
At present, rheumatoid arthritis patients must be viewed at a high risk for coronary artery disease and should have regular cardiovascular assessment, including lipid profile and blood pressure. Dr Maher pointed out that the patient with rheumatoid arthritis may not present with the usual angina pectoris symptoms due to their reduced capacity for exercise.
Thus, traditional tests such as stress ECG may be limited, while newer modalities – such as CT coronary angiography – are likely to become more widely available, given the combination of high accuracy and the non-invasive nature of the test.
Economic and social impact
Prof Carol Black, the National Director for Health and Work in the UK, presented an overview of work and musculoskeletal diseases. Musculoskeletal disease is the second-leading cause of sickness absence and long-term incapacity in Ireland, with an estimated 14,000,000 working days lost last year due to ill health overall.
It is estimated that the direct cost of musculoskeletal disease due to sickness absence and disability is € 750,000,000 per annum in Ireland.
Rheumatoid arthritis in particular is a serious concern to rheumatologists, as only 22 per cent of rheumatoid arthritis patients in Ireland remain in full-time employment. There is now clear evidence that intervention in the first few months of disease has a major impact on maintaining rheumatoid arthritis patients in the workforce.
While there are obvious economic benefits to this, it is important to realise that work is also a strong social determinant of health. It is imperative that the patients with all musculoskeletal disorders have early intervention to maintain them in the workforce.
Replacing the sick note
In the UK, the ‘sick note’ is being replaced with the ‘fit note’. This has resulted in the Fit for Work Services, which provide early interventions to actively manage the return of patients with musculoskeletal disorders back to work. The fit note was designed to create a management plan for a return to work, rather than an all-or-nothing scenario practised under the old sick note system.
The fit note outlines directions for a graded return to work, in addition to guidance on hours of work, change of duties and adaptations in which the employer needs to engage. The roll-out of this new scheme has been underpinned with planned changes within undergraduate and postgraduate training so that GPs can play a more active role in managing work disabilities.
Prof Black advocated a fit-for-work programme for Ireland that would involve a national plan for musculoskeletal disorders led by a national clinical director. She recommended a change from our current sick-note system to a fit note, with early diagnosis and management of sickness absence due to musculoskeletal disorders.
Arthritis in children
Prof Helen Foster outlined the current state of managing inflammatory arthritis in children. The commonest condition is juvenile inflammatory arthritis which, like many adult diseases, was previously thought to be relatively benign. It is estimated that there are 1,000 juvenile inflammatory arthritis patients in paediatric services in Ireland and 700 adult patients with juvenile inflammatory arthritis.
It is now clear that juvenile inflammatory arthritis is a chronic disorder that is not benign. Joint damage occurs early and it is recognised that early aggressive treatment provides a window of opportunity to obtain tight control and better outcome in terms of overall health and functioning for children with inflammatory arthritis. Methotrexate is the drug of choice in juvenile inflammatory arthritis, but all of the biologic agents used in adults are currently being used in juvenile inflammatory arthritis with good results.
There are many challenges for these children as they grow up, with 1/3 continuing to have active disease and 1/3 having disability problems, despite eventually going into remission of inflammation. Adult patients with JRA are best managed by a transition model run by paediatric and adult rheumatologists. It was highlighted that there is only one paediatric rheumatologist through the whole of Ireland, which makes provision of these services extremely difficult.
The lack of services for children prevents implementation of modern standards of therapy, thus exposing paediatric patients to irreversible loss of joint damage and function, with consequent high risk of permanent disability.
Joint replacement might be best arthritis treatment
December 8, 2010 — Arthritis is a group of conditions involving damage to the joints of the body. There are more than 100 different forms of arthritis.
The most common form, osteoarthritis, is a result of trauma to the joint, infection of the joint – or age. Other arthritis forms are rheumatoid arthritis, psoriatic arthritis, and autoimmune disease.
Arthritis is the most common cause of disability in the United States. More than 20 million people with arthritis have severe limitations that affect their function on a daily basis. Each year, arthritis results in nearly 1,000,000 hospitalizations and close to 45,000,000 outpatient visits to health care centers.
Causes of arthritis include injury metabolic abnormalities, hereditary factors, the direct and indirect effect of infections and a misdirected immune system with autoimmunity. Symptoms of arthritis include pain, limited function of joints, and inflammation of the joints, which is characterized by joint stiffness, swelling, redness, and warmth. (SOURCE: The Arthritis Foundation)
MYTHS: How much do you really know about arthritis? Did you know it’s a two billion dollar a year business?
Many medications promise miracle cures, but doctors say a quick fix with unproven pills, devices, and minimally invasive surgery may be a waste of money if you have an advanced form of arthritis.
The best option: joint replacement surgery.
When joint replacement surgery occurs, the artificial surfaces of the joint replacement are shaped in such a way as to allow joint movement similar to that of a healthy natural joint.
MYTH # 1: ARTHRITIS ONLY AFFECTS OLDER PEOPLE!
The truth: Some forms of arthritis do mainly affect elderly people, including the most common, osteoarthritis. Yet many types can affect younger people, and joint injuries at any age can lead to osteoarthritis. Currently more than half of the population with arthritis is under 65.
MYTH # 2: WEATHER AFFECTS ARTHRITIS SYMPTOMS!
The truth: Many people with arthritis believe that cold and dampness can set off joint symptoms. Indeed, according to the Arthritis Foundation, nearly half of arthritis patients think their flare up happens when they have to take their sweaters out off the closet.
MYTH # 3: EXERCISE BOOSTS ARTHRITIS PAIN!
The truth: Regular moderate exercise can help prevent and treat arthritis. Exercise promotes function and mobility, controls weight and strengthens the muscles that support the joints. Though you may want to avoid high-impact exercises if your knees bother you, low-impact exercises such as walking, tai chi or aquatics are all beneficial. Talk to your physician about the best exercise regimen for you. Pool therapy has been shown to cause improvement in mobility in arthritic joints.