Structure modifying Gene therapy will prove beneficial and we are getting closer to that - Prof. Syed Atiqul Haq


 Rheumatology Conference Proceedings-III

Structure modifying Gene therapy will
prove beneficial and we are getting
closer to that - Prof. Syed Atiqul Haq

Steroids reduce bone mineral density, leads to
early bone loss hence early interventions
become crucial - Ms. Dierdre Shawe

LAHORE: Prof, Kamran Hameed along with Dr. Tariq Mian and Dr. Mahfooz Alam chaired the second scientific session during the Rheumatology conference held at Lahore from October 12-14th 2012. Dr. Javed Malik was the first speaker who talked about back pain- is it a rheumatic disease. Its prevalence, he said, ranges from 0.1 to 1.4%. There is significant burden of disease and treatment is unsatisfactory. He pointed out that there is a 14% probability in case of inflammatory back pain. It has positive response to NSAIDs. Aim of treatment is relief form pain, stiffness, fatigue, restoration of fitness and prevention of complications. He then talked about prognostic factors and said that in male gender there is early onset. Treatment consists of biologics which were introduced in 2000, patient education, exercise, physical therapy, and rehabilitation. Lately patient education groups have become quite useful.
Use of NSAIDs provides 80% relief from pain. Sulfasalazine is being used a lot and it has 59% response. Infliximab results in significant improvement. Back Pain, he stated is not uncommon, there is delay in diagnosis and recognition. Early recognition can improve functions and results. His suggestion was that patients should be referred to rheumatologists for proper guidance and management.
Prof. Syed Atiqul Haq from Bangladesh made a presentation on disease modification of osteoarthritis - a myth or reality. He pointed out that there are about sixteen guidelines on this topic including guidelines by NICE from UK, ACR, and EULAR. He also talked about wear and tear, molecular pathogenesis; molecules tested by chance and targeted therapies. He then referred to the use of Neutriceuticals. Osteoarthritis, he said, is a genetic disease and in 39-78% of patients genetic factors are associated. In fact it is a multifactorial disease. Speaking about future diagnosis and therapy he pointed out that specific molecular biomarkers will emerge as a tool for pre-clinical diagnosis. In Gene therapy structure modifying therapy will prove beneficial and we are getting closer to that, he remarked.
Ms. Dierdre Shawe from UK talked about steroid induced osteoporosis. This, she said, is a significant problem. Many patients getting steroids are not appropriately evaluated and treated to prevent the risk of osteoarthritis. About 1% of population is on glucocorticosteroids. Steroids were first used in 1948 with dramatic results. However, use of high dose had serious side effects. For almost thirty years there were no guidelines for use of steroids. They are effective treatment for inflammatory diseases. Now there are a number of guidelines for use of steroids. They do reduce bone mineral density, leads to early bone loss and early interventions become crucial. Most common cause of secondary osteoporosis is steroids. They reduce new bone formation and increase apoptosis. He also talked about reduced intestinal absorption of calcium, increased serum calcium loss, impact of steroids on fracture risk. With the use of steroids, hip fracture and vertebral fracture risk are increased. About 25% of patients on steroids will develop osteoporosis. Bone quality is also reduced in patients on steroids. He also talked about clinical impact of osteoporosis on spine as these patients have an increased tendency to fall. Almost 19% of hip fractures need long term nursing care. Early intervention with bone protection therapy is important. Higher dose of steroids increase risk of fractures. Fracture risk, she said increases with the start of steroids and decrease with the stoppage of therapy. Inhaled steroids are better. One should start bone protection therapy with the start of steroid therapy in patients over sixty five years of age with prior fragility of fractures. Recommend good nutrition and consider alternate route. Treat all patients over sixty five years of age with extra care. She also talked about newer therapies. Fracture risk, she further stated matters a lot She then referred to FRAXTOOL developed by WHO which is a computer based risk assessment score. It also has certain problems which were discussed in detail. She then talked about ACR guidelines and said that biphosphonates are effective in steroid induced osteoporosis. Recommend these patients good nutrition, calcium, Vitamin D. Take into account cost benefit and tolerance. Osteonecrosis of jaw is associated with long term use of allendronates. Her conclusions were that osteoporosis is under treated. Inhaled intermittent steroids, she opined, are safe. One should treat all patients over sixty five years and all post menopausal women but there is no consensus on time for withdrawal of steroids. Prof.Kamran Hameed in his concluding remarks said that BMD is not necessary in red zone. Investigate in moderate cases and start treatment of patients who fall in green zone.

Synovial fluid analysis and
injection techniques workshop

In the afternoon Prof. Terence Gibson conducted a workshop on synovial fluid analysis and injection techniques. He talked about steroids injections use and mentioned hydrocortisone in tendons, depot methyl Prednisolone mixed with 1% lignocane for joints. Talking about the shoulders he mentioned about supraspinatus tendonitis, bicipital tendonitis and frozen shoulder. In UK microscope is used for looking at joints. In the Emergency Room, all trainee rheumatologists use it. We have microscope in every emergency department. He was of the view that all rheumatology departments should have hand wash facilities. He also talked about aspiration of joint effusion for rapid diagnosis or therapeutic effect. He then referred to microscopy of fresh sample for cell density and felt that one should have microscope in the department to see for infections.

Treat to target approach in Rheumatoid Arthritis

Prof. Kamran Hameed along with Dr. Azra Ali chaired the first session on third day of the conference. Dr. Drerdre Shawe from UK was the first speaker who talked about treat to target approach in Rheumatoid Arthritis- the UK experience. To achieve remission or low disease activity is target, suppressing inflammation does not stop disease progression. Traditional approach, it was stated, has been to treat patient symptomatically and referral to specialist team was delayed. After one year’s use of DMARDs, joint erosion was seen in 30% in one study which increased to 70% after second year. The presentation discussed in detail inflammation, disability, radiological damage and emphasized the importance of re-evaluation of approach in treating rheumatoid arthritis. DMARDs used in combination gives better results as compared to monotherapy. MRI, CT, better images help in early diagnosis. In case of early effective therapy, joint destruction is reduced and checked effectively. There is a window of opportunity in early referrals. Early aggressive therapy is indicated for long term better results. There is a steering committee looking after Treat to Target recommendations. It should be a shared decision between the patient and rheumatologist regarding treatment. In long term it offers better quality of life and health.
In treating Rheumatoid Arthritis one should reach a target. It should be clinical remission, ensure assessment on regular basis, and adjust treatment after every three months until target is achieved. Involve the patient in treatment decisions, audit the service and ensure education of professional healthcare colleagues and hospital staff. She laid emphasis on early arthritis clinics, optimizing use of assessment tools and diagnostic ultrasound. Patients with RA visit the GP three to four times before being referred to specialist care. More efficient effective referrals from many early arthritis clinics is ensured. The best way to process referrals need extra manpower; imaging with portable ultrasound can be incorporated. Diagnostic Ultrasound and MRI are not rivals in showing synovitis and erosion of joints. MRI is more expensive but less operator dependent. In contrast to MRI sonography provide no information on bone marrow oedema. Diagnostic ultrasound is becoming useful. Primary objective is remission with no inflammatory symptoms. Clinically diagnosed as remission patients, still show evidence of synovitis on image. Training rheumatologist in use of ultrasound is difficult. Portable machines are expensive and they have no time in busy clinics to do ultrasound as well. It was emphasized that tight control needed for T2T can achieve remission or low disease activity. It is the only way forward in RA.
Dr. Mahboobur Rehman from USA talked about safety of biologic DMARDS- experience from the registries. He described the different classes of TNF inhibitors, Meta analysis of safety results from various RCTs and pointed out that risk of serious adverse events is not significantly increased with biologics. Most did not increase risk of serious infections. He also talked about short term vs. long term safety profile. As regards short term safety profile approved for RA, some adverse events are rare and occur in long term use. Registries, he further pointed out have the benefit of large sample size than RCTs. Sustained long term follow up is possible and there is low drop out. But the disadvantages is that it is not randomized, there can be biases and missing data. However, there is low discontinuation rate due to adverse events. As regards serious infection, results from registries report it 40-50/1000 patients. Risk of serious infections was lower with TNF-I treated RA patients and hospitalization time was also reduced. Higher RA disease activity is associated with increased risk of infection. It means you need to control your disease as well. There was a high risk of TB in both RA and AS patients treated with Anti TNF-mAbs. He also talked about risk of malignancy in RA patients and cardiovascular risk and adverse events is lower as in patients on TNF are compared with methotrexate.
Is safety an issue with biological drugs was the topic of presentation by Dr. Abdus Samad from Islamabad. He also discussed how to assure the quality of drugs. He pointed out that now we have special laws for testing and assuring quality of biological drugs. How to control quality of molecules is very sophisticated. After the expiry of patents many new biosimilars are being introduced. They originate from living cells and safety profile may differ from batch to batch. We assure that the data provided is biologically safe. The dossier defines those asking for registration will have to provide answers to all the questions in the new law including complete manufacturing process and quality control as well. Raw material will also be tested. Clinical trial data must be published only then it will be accepted. Bioavailability, bio sensitivity safety and efficacy will all be assured. Drug Registration Board will have experts using biological drugs. Hence rheumatologists will be sure that drugs you are using are of quality, he added.
Prof. Abid Farooqui along with Prof. Javed Akram chaired the last session. Prof. Kamran Hameed gave details of METOR (Measurement of Efficacy of Treatment in the Era of Outcome in Rheumatological) experience. He pointed out that as regards prognostic markers at presentation, we see severe disease but the GPs may be seeing a much milder disease. Most of our patients are on methotrexate and 2% of our patients are on biologicals. He was of the view that using this tool is easy, it will provide central data base which can be used for research. It will enhance and strengthen relationship between doctors and Rheumatological patients. He suggested that all of us should start recording the data.
Dr. Imran Tanveer discussed new trends in serological and diagnostics, consequences of wrong ANA testing, strategy for ANA diagnostics, special advantages of BIOCHIP technique. IIFT, he opined, was the best method for ANA screening. Dr. Hans Rasker from Netherlands talked about managing difficult LUPUS. He discussed in detail management of severe and refractory SLE. His presentation was based on 196 SLE patients. They had infection and renal involvement. Pakistan has less joint involvement, less skin and kidney involvement as compared to Netherlands. Asians, he said, have high rate of renal involvement and between 6-40% patients die. General treatment measures include use of drugs, biologicals. Half of the SLE patients at some stage have severe lupus. He also talked about Cardiac SLE, Gastrointestinal SLE and Haematologic Severe SLE. All have different diagnosis. Gastrointestinal SLE has pulmonary and nervous system involvement. Digital gangrene, he said, should be treated with steroids. In some patients eyes and ears can be involved. He also referred to retinal vasculitis and renal involvement. As regards general treatment measures, he said that it has to be specific to each patient and it cannot be generalized. It also depends on which organ is involved. One should exclude infection and other causes. It has an unpredictable course of disease.
Mild SLE can be managed with HCQ of DMARAD alone or with low dose of steroids. One should start with a low dose. HCQ results in 50% reduction of dose. Methotrexate is as effective as HCQ in mild to moderate SLE. Leflunamide results in 20% remission after six months treatment. Cyclophosphomide dose depends on severity of the disease and weight of the patient. Azathioprime is a steroid sparing drug. MMF is as good as HZA for maintenance therapy. It is not effective in external lupus. Include methotrexate as a therapeutic option for refractory SLE and it has been included and recommended by both ACR and EULAC in their recommendations. He also referred to ongoing studies with interferon therapy and anti IL6 and IL10 molecules. Patient should visit the treating physician once in three months. Blood pressure and blood glucose control is important. He also suggested yearly bone denometry. Sun exposure as prophylaxis and topical steroids are effective. Methotrexate is as effective as HCQ and Thalidomide is also being used in severe SLE. Continuing, he said, that severe SLE can be treated by standard approaches. Every patient needs specific treatment. Every university needs to establish a rheumatology department and rheumatology education should be included in medical schools and nursing schools. He also laid emphasis on cooperation between countries to learn from each other.

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