Musculoskeletal System 2 Study Pack

6PY011 Musculoskeletal System 2 Study Pack 2025-26 Musculoskeletal System (2) The diagnosis and therapeutic management of musculoskeletal conditions. Facilitators References Fatimah Abbas f.abbas4@wlv.ac.uk Required references: • 5PY022 Musculoskeletal System TBL pack • British National Formulary (current edition). • The Summary of Product Characteristics for all drugs mentioned in this study pack, which may be accessed via the following link to the electronic Medicines Compendium: http://www.medicines.org.uk/emc/ • Medical Pharmacology and Therapeutics, 4th edition Saunders Elsevier 2014, edited by Waller, Sampson, Renwick and Hillier • Clinical Pharmacy and Therapeutics, 6th edition, Churchill Livingston 2018, edited by C. Whittlesea and K. Hodson • Community Pharmacy, 5th Edition, Elsevier, by Paul Rutter. • Minor Illness or Major Disease, 6th Edition, Pharmaceutical Press, by Brian Addison et. al. Mumtaz Jivraj mumtaz.jivraj@wlv.ac.uk Aikaterini Karakoula a.karakoula@wlv.ac.uk Study pack based on work by Dr Mike and Jan Daly Additional reading: • An introduction to Health Psychology, 4th edition, Pearson Books 2016, edited by Morrison and Bennett. • Clinical skills for pharmacists: a patient focused approach, 3rd edition, Elsevier 2011, edited by Tietze. Learning Outcomes: 1. To understand the diagnosis, therapeutic and non-drug management of major musculoskeletal conditions. 2. To understand advanced drug delivery design, such as biologics and their use in patients with musculoskeletal conditions. 3. By the end of the cycle - to review the appropriate clinical management of patients based on patient factors and application of the evidence base. 1 6PY011 Musculoskeletal System 2 Study Pack 2025-26 Contents Musculoskeletal Conditions in the Community Pharmacy.……….……..………. 3 When to Refer to the GP …………………………………………………… 3 Metabolic Bone Disease ……………………………………………………………. 5 Osteoporosis.……………………………………………………………….….…….. 5 Osteoarthritis.…………………………..……………………………………..…..…. 9 Rheumatoid arthritis (RA) ..…………………………………………….….…….…. 10 Conventional DMARDs …………………………………………………….. 11 Biological DMARDs.…..…………………………………………….…….… 13 Gout …………………………..…………………………………………………….… 18 2 6PY011 Musculoskeletal System 2 Study Pack 2025-26 Musculoskeletal Conditions in the Community Pharmacy Musculoskeletal disorders are those that affect bones, muscles, or soft tissues (tendons and bursae). There are several musculoskeletal conditions that are frequently encountered in a community pharmacy. Although the majority of these are caused by injury, some are the result of organic disease. The most common presenting signs and symptoms are pain, swelling and immobility. Management options are pharmacological or nonpharmacological. Non-pharmacological options include: • PRICE (protect, rest, ice, compression & elevation) • Application of heat or cold • Physiotherapy • Posture and exercise • Joint supports • Lifestyle modification • Weight loss • When sleeping, use a firm mattress Figure 1: Diagram showing the appendicular and axial skeleton Pharmacological treatment options include: • Paracetamol • Topical NSAIDS e.g. ibuprofen 5% gel • Oral NSAIDS e.g. ibuprofen 400mg tablets • Mild opioids e.g. co-codamol 8mg/500mg tablets When to refer to the GP Most musculoskeletal problems are self-limiting. If a patient has managed to come into the pharmacy, they are unlikely to have a serious injury. However, whenever a patient presents in a pharmacy, you must know the common signs and symptoms that could indicate a serious pathology or injury requiring referral. Some key red flags in patients presenting with back pain that require urgent referral to a GP and/or A&E are: • Pain following major trauma such as vehicle accident • New back pain in patients aged under 20 years or over 50 years • Weight loss • Past medical history of malignancy • Associated bladder or bowel symptoms • Widespread or progressive motor weakness in the legs or gait disturbance 3 6PY011 Musculoskeletal System 2 Study Pack 2025-26 Task 1: complete the tables below. You may find it useful to refer to the textbooks “Community Pharmacy” and/or “Minor Illness or Major Disease”, referred to at the front of this study pack. What signs or symptoms require referral in a patient with a soft tissue or muscle injury and why? Signs or symptoms to refer Rationale for referral Aside from the red flags listed above, what other signs or symptoms require referral in a patient reporting back pain and why? Signs or symptoms to refer Rationale for referral Clinical guidelines • • Throughout this study pack, you will need to familiarise yourself with clinical guidelines – both local and national. Pharmacists must be aware of the different types of guidance issued by the National Institute for Health and Care Excellence (NICE) [particularly NICE guidelines [NGs] and technology appraisals guidance [TAGs]. Both types of guidance are referred to in this pack. A summary of the NICE guidelines can be found at the following link: https://www.nice.org.uk/about/what-we-do/our-programmes/nice-guidance • Task 2: What is the main difference between NICE Guidelines and NICE Technology Appraisal • Guidance? 4 6PY011 Musculoskeletal System 2 Study Pack 2025-26 Metabolic Bone Disease Osteopenia vs. Osteoporosis – A recap from 5PY022 Osteopenia is a reduction in the mineral content of bone, whereas osteoporosis is a reduction in actual bone mass. The onset of both conditions is often age-related, and they can cause bones to fracture easily. The main causes of osteoporosis include: • Postmenopausal oestrogen deficiency • Age-related deterioration in bone homeostasis • Long term levothyroxine use. Subclinical hyperthyroidism may be associated with bone loss. To minimise the risk of osteoporosis, dosage of levothyroxine sodium should be titrated to the lowest possible effective level. • Prolonged glucocorticoid therapy, with associated bone loss • Myeloma (a type of cancer that develops from cells in the bone marrow) Osteoporosis Diagnosis Diagnosis of osteoporosis is dependent on multiple factors: • Clinical history to assess risk factors; females, increasing age, low BMI, maternal history of osteoporosis or fragility fracture, history of steroid use >5mg/day, hyperthyroidism, alcohol and smoking, malabsorption causing decreased calcium intake. • Fracture risk: o QFracture® is a calculator to work out a patient’s risk of developing any osteoporotic (i.e. hip, wrist, shoulder or spine) fracture or hip fracture over 10 years by answering some simple questions. o QFracture®-2016 has been developed for the UK population and is intended for use in the UK. All medical decisions need to be taken by a patient in consultation with their doctor. QFracture is recommended for use in England and Wales. o It considers age, gender, medical history, smoking and alcohol intake and specific medication use. Risk is given as a percentage score. o FRAX® is another risk tool (fracture risk assessment tool that is similar to QFracture. • DEXA (dual-energy X-ray absorptiometry) scan; this is a bone density scan performed using low dose X-rays. o Patients at high risk of a fracture should be offered a DEXA scan to confirm osteoporosis. o Patients at intermediate risk whose fracture risk is close to the recommended threshold and who have risk factors that may be underestimated by FRAX®, such as people taking high doses of oral corticosteroids, should be offered a DEXA scan. o Bone Mineral Density (BMD) is calculated using a T score: ▪ > -1 is healthy, with no evidence of osteoporosis ▪ -1 < -2.5 slightly decreased BMD (osteopenia) with risk of fracture ▪ < -2.5 is osteoporosis, which requires therapeutic management and prevention of fractures • X-ray; although this is commonly performed after a fracture which later results in a diagnosis of osteoporosis. • Blood tests: 5 6PY011 Musculoskeletal System 2 Study Pack o o o o 2025-26 Calcium Phosphate Alkaline phosphatase Thyroid function tests (TFTs) Differential Diagnoses Osteoporosis may be mistaken for other conditions such as: • Osteomalacia • Hyperparathyroidism • Multiple myeloma • Paget’s disease • Scurvy • Sickle Cell Disease (SCD) Pharmacological Management • • • • • There are currently no clinical guidelines produced by NICE for the stepwise management of osteoporosis, however there are various NICE TAGs in place that support the use of several treatments discussed below. First-line treatment is commonly bisphosphonates o A bisphosphonate should be offered to people with a BMD T-score of -2.5 or lower, if appropriate and there are no contraindications. o Not all bisphosphonate formulations are licensed for use in males. Bisphosphonates are usually paired with calcium and vitamin D (colecalciferol) replenishment: o 400units colecalciferol /day if adequate calcium intake o 400units colecalciferol /day + 1000mg calcium /day if inadequate calcium intake. NB greater doses of colecalciferol are advised for elderly or house-bound patients. o There are multiple preparations available on the market, allowing patient preference dependent on: ▪ Taste/flavour ▪ Dosage form e.g. chewable tablet or soluble tablet ▪ Frequency of administration Selective oestrogen receptor modulators (SERMs) have agonist actions on some tissues and antagonist actions on others. For example, raloxifene has agonist actions on bone and the cardiovascular system, but antagonist actions on mammary tissue. Raloxifene’s mechanisms include: o Increased osteoblast activity in a dose-dependent manner o Reduced activity of osteoclasts o It undergoes extensive first-pass metabolism, so its bioavailability is low (2%), but it is well distributed around the body. o See the link below for more information: Overview | Raloxifene for the primary prevention of osteoporotic fragility fractures in postmenopausal women | Guidance | NICE Strontium ranelate – this reduces osteoclast activity, which results in decreased bone resorption. It also increases osteoblast activity which increases bone formation. o Limited to use in patients in whom other treatments are not tolerated or contraindicated. o Can cause allergic reactions, particularly severe cutaneous adverse reactions (SCARs). 6 6PY011 • • • Musculoskeletal System 2 Study Pack 2025-26 PTH and PTH fragments: These increase bone mass by paradoxically stimulating osteoblast numbers and decreasing osteoblast apoptosis. They act on PTH-1 receptors (GPCR), activating adenylate cyclase, PLA2, PLC and raise intracellular Ca2+ levels. These are given subcutaneously and are generally well tolerated. Examples include: o Teriparatide – the most widely available with several biosimilars on the market. Overview | Raloxifene and teriparatide for the secondary prevention of osteoporotic fragility fractures in postmenopausal women | Guidance | NICE o Abaloparatide is a new drug licensed for use in post-menopausal patients with a very high risk of fracture. It is not currently available widely through the NHS but may be prescribed via a patient access scheme. See the link below for more information: Overview | Abaloparatide for treating osteoporosis after menopause | Guidance | NICE Monoclonal antibodies o Denosumab (as Prolia®)– a human monoclonal antibody that binds to RANKL to inhibit osteoclast formation, which results in decreased bone resorption. It is licensed for postmenopausal patients who are intolerant to or have a contraindication to bisphosphonates and are at high risk of a fracture. See the link below for the NICE TAG: Overview | Denosumab for the prevention of osteoporotic fractures in postmenopausal women | Guidance | NICE o Romosozumab – a humanised monoclonal antibody that inhibits sclerostin, which leads to increased bone matrix production by osteoblasts. It also decreases bone resorption, with an overall improvement in bone structure and strength. o This is a new drug that is not currently available widely through the NHS but may be prescribed via a patient access scheme. It is restricted to patients who are unable to tolerate other osteoporosis treatments. See the link below for more information: Overview | Romosozumab for treating severe osteoporosis | Guidance | NICE Hormone Replacement Therapy (HRT) – offered to post-menopausal patients who desire symptomatic relief menopause. HRT is useful for its additional impact on bones, but it is NOT a selective or specific treatment for osteoporosis. Non-pharmacological Management • • • • • Exercise; strength-based and weight-bearing mobility exercises Smoking cessation – smoking is a risk factor for a fragility fracture Limiting alcohol intake – increased alcohol consumption is a risk factor for a fragility fracture Ensuring adequate dietary calcium (at least 700mg/day) and vitamin D intake Weight management – obesity is associated with increased stress on joints, which can result in a fragility fracture 7 6PY011 Musculoskeletal System 2 Study Pack 2025-26 Task 3: Using the BNF and SmPCs, identify and list the bisphosphonate formulations that are licensed for use in males. Task 4: What monitoring is required in patients diagnosed with or at risk of osteoporosis? You may find it useful to refer to “Clinical Pharmacy and Therapeutics” as well as the BNF and SmPC. 8 6PY011 Musculoskeletal System 2 Study Pack 2025-26 Osteoarthritis (OA) – A recap from 5PY022 Diagnosis Osteoarthritis is diagnosed clinically, i.e. it is based upon signs and symptoms and does not usually require radiological imaging. The following criteria are used to inform a diagnosis: • Is 45 or over and • Has activity-related joint pain and • Has either no morning joint-related stiffness or morning stiffness that lasts no longer than 30 minutes Differential Diagnoses OA may be mistaken for other conditions such as: • Inflammatory arthropathy • Gout • Fibromyalgia • Bone fracture of the adjacent joint • Malignancy • Sciatica (if OA of the hip) Non-pharmacological Management The following advice if recommended as first line treatment for patients with osteoarthritis: • Mobility aids for patients with OA affecting the legs or knees • Exercise; muscle strengthening and flexibility to reduce joint pain and damage • Weight management – obesity is associated with increased stress on joints, which can increase joint degradation. Any loss of weight is beneficial; see the guidance from NICE for further information: Overview | Obesity: identification, assessment and management | Guidance | NICE Pharmacological Management Medication may be used alongside non-pharmacological measures to manage osteoarthritis; treatment should be limited to the lowest effective dose for the shortest possible time. Management options include: • Topical NSAIDS for OA affecting joints • Oral NSAIDS if topical formulations are unsuitable or ineffective. o A gastro-protective agent must be co-prescribed e.g. a PPI • Intra-articular corticosteroid injections if other treatments are unsuitable or ineffective. o Relief is short term and may range from 2-10 weeks. Paracetamol and weak opioids are NOT recommended except in the following circumstances: • Infrequent use for short term analgesia • Other treatment options are unsuitable or ineffective. Surgical Management Patients should be referred for hip, knee or shoulder joint replacement if all other treatment options are unsuitable or ineffective AND if the symptoms have a detrimental impact on their quality of life. Refer to the following NICE guideline for further information on the management of OA: Overview | Osteoarthritis in over 16s: diagnosis and management | Guidance | NICE 9 6PY011 Musculoskeletal System 2 Study Pack 2025-26 Rheumatoid Arthritis (RA) Diagnosis • • • Signs and symptoms include: o Joint pain, stiffness and swelling o Crippling deformities o Atrophy of muscles, bones, and skin adjacent to affected joints Referral to a rheumatologist is required for suspected RA to confirm diagnosis, evaluate disease activity and commence treatment. However, there is no single European or international method of diagnosing rheumatoid arthritis and no single diagnostic test to detect it. Investigations recommended include: o Clinical history; particularly family history, presence of systematic and extra-articular features o Blood tests: ▪ Rheumatoid factor ▪ Anti-Cyclic Citrullinated Peptide (CCP) antibodies ▪ Full blood count to review markers of inflammation ▪ C-Reactive Protein (CRP) ▪ Liver function tests (LFTs) ▪ Urea & electrolytes (U&Es) o X-ray of hands and feet Refer to the NICE guidelines for further information: Overview | Rheumatoid arthritis in adults: management | Guidance | NICE Task 5: Define synovitis: Task 6: You will need to have a good understanding of the word’s “remission” and “active disease”. Consider these two words whilst you find out what the DAS-28 score is and how is it used to assess disease severity. 10 6PY011 Musculoskeletal System 2 Study Pack 2025-26 Differential Diagnoses RA may be mistaken for other conditions such as: • Osteoarthritis • Systemic lupus erythematosus • Fibromyalgia • Infective arthritis • Polymyalgia rheumatica • Psoriatic arthritis, reactive arthritis or septic arthritis Pharmacological Management We have already discussed first line treatment of RA in your stage 2 MSK TBL - RECAP THESE • • • • Treatment of RA aims primarily to reduce inflammation. NSAIDs may be used for control of symptoms in the initial management of the condition or during an acute flare-up, but the main approach to treatment is to achieve disease remission or low disease activity if remission cannot be achieved, and to improve the patient's ability to perform daily activities. Conventional DMARDs (referred to by NICE as cDMARDs) include drugs such as methotrexate, leflunomide and sulfasalazine and should be offered as first-line treatment in RA. Other drugs which affect the immune response and must be used under specialist supervision include the biological DMARDs (often referred to as ‘biologics’); a group of drugs including monoclonal antibodies and soluble receptors that modify the disease process by blocking key protein messenger molecules (such as cytokines) or cells (such as B-lymphocytes). Targeting key components of the immune system allows efficient suppression of the pathological inflammation cascade that gives rise to RA symptoms and subsequent joint destruction. Conventional DMARDs • The choice of a cDMARD should consider any co-morbidities and patient preference. • Methotrexate, sulfasalazine, intramuscular gold, and penicillamine are similar in efficacy. However, methotrexate and sulfasalazine may be better tolerated. Azathioprine, ciclosporin and cyclophosphamide are considered more toxic, and they tend to be used in cases that have not responded to other cDMARDs. • NICE [2018] recommends that for adults with newly diagnosed active RA: o Offer first-line treatment with cDMARD monotherapy using oral methotrexate, leflunomide or sulfasalazine as soon as possible and ideally within 3 months of onset of persistent symptoms. o The dose of the cDMARD should be escalated as tolerated o Consider hydroxychloroquine for first-line treatment as an alternative to oral methotrexate, leflunomide or sulfasalazine for mild or palindromic disease o Escalate dose of the cDMARDs as tolerated. • Short-term ‘bridging treatment’ with glucocorticoids (oral, intramuscular or intra-articular) should be considered when starting a new cDMARD. 11 6PY011 Musculoskeletal System 2 Study Pack 2025-26 Bridging treatment is where glucocorticoids are used for a short period of time when a person is starting a new DMARD, intended to improve symptoms while waiting for the new DMARD to take effect (which can take 2 to 3 months). Glucocorticoids should be restricted to short-term treatment for managing flares in adults with recent-onset or established disease to rapidly decrease inflammation. In patients with established RA, long-term treatment with glucocorticoids should only continue when the long-term complications of glucocorticoid therapy have been fully discussed, and all other treatment options (including biological and targeted synthetic DMARDs) have been offered. Patient taking cDMARDs require regular monitoring with blood tests. These are carried out in secondary care (hospital) but may be done in primary care under a shared care agreement (which outlines ways in which the responsibilities for managing the prescribing of a medicine can be shared between the specialist and a primary care prescriber). o • • Task 7: list the monitoring requirements and any patient and carer advice for each of the following conventional DMARDs - this is key patient safety information. You may find it useful to refer to the BNF, SmPC and “Clinical Pharmacy& Therapeutics”, referred to at the start of this study pack. • Methotrexate • Sulfasalazine • Sodium aurothiomalate • Leflunomide (include the washout procedure) • Penicillamine • Hydroxychloroquine 12 6PY011 Musculoskeletal System 2 Study Pack 2025-26 Biological DMARDs Note that all these agents should be used under specialist supervision and must be prescribed and dispensed by brand name. • • • • • • Over recent years, the use of so-called ‘biologic’ agents for the treatment of RA, based on immunologically active agents, has become a major new route for the effective treatment of this debilitating condition. Patient-focused information about biologics for the treatment of RA has been produced by the National Rheumatoid Arthritis Society (NRAS) and can be accessed at: https://www.nras.org.uk/biologics Biological DMARDs are expensive and so their availability on the NHS is primarily controlled by NICE TAGs. The introduction of the biological DMARDs has generated the development of a range of ‘biosimilar’ medicines. A biosimilar medicine is a biological medicine which is highly similar to another biological medicine already licensed for use. It is a biological medicine which has been shown not to have any clinically meaningful differences from the originator biological medicine in terms of quality, safety and efficacy. These agents have the potential to offer the NHS considerable cost savings and widen access to more innovative technologies and treatment options. Due to the sophisticated and complex manufacturing processes involved in the production of biologics, biosimilars are not classed as ‘generic’ medicines, because they are not absolutely identical to the original biologic medicine. The characteristics of biologic drugs cannot, in general, be reproduced exactly, so to gain approval for clinical use, biosimilar medicines must demonstrate that they are as safe and effective and of the same quality as the original reference medicine. Biosimilar medicines have been developed in anticipation of the impending patent expiry of innovator biologic drugs. Read the information in the current BNF on prescribing biologic and biosimilar medicines in the section containing guidance to prescribers, available using the following link: https://bnf.nice.org.uk/guidance/guidance-on-prescribing.html • • • In January 2016 NICE published Technology Appraisal 375 (TA375) which provides guidance on seven biological technologies for the treatment of RA. These are adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept for rheumatoid arthritis not previously treated with DMARDs or after conventional DMARDs only have failed. The guidance can be viewed at this link: https://www.nice.org.uk/guidance/ta375 NICE reviewed the evidence for this TA in September 2019 and is currently updating the guidance for people with moderate disease. The recommendations in this TA also apply to biosimilar products of the technologies that have a marketing authorisation allowing the use of the biosimilar for the same indication. The technologies in TA375 have different mechanisms of action: o Infliximab, adalimumab, golimumab, certolizumab pegol and etanercept all inhibit the activity of tumour necrosis factor (TNF)-alpha, a pro-inflammatory mediator that is partly responsible for damage to the joints in RA 13 6PY011 Musculoskeletal System 2 Study Pack o o 2025-26 Abatacept is a selective modulator of the T-lymphocyte activation pathway. It binds to molecules on the surface of antigen-presenting cells, preventing full activation of the T-lymphocytes and interrupting the inflammatory process Tocilizumab inhibits the activity of interleukin-6 (IL-6), a pro-inflammatory cytokine that is also partly responsible for joint damage in RA The science of monoclonal antibodies will be covered in a separate lecture by Dr Jones, and in more depth in the biotechnology/molecular biology lecture series of this strand. Naming of Monoclonal Antibodies (mAbs) • Monoclonal antibodies are named based on a specific structure developed by the International Non-proprietary Names (INN) Working Group, under the direction of the World Health Organisation. This structure consists of a prefix, substem A, substem B, and suffix. Naming scheme: • prefix + substem A + substem B + suffix The prefix does not follow any specific criteria, except that it must distinguish a particular antibody from other products. Figure 2: Structures and sites of action of technologies appraised in NICE TA375 • • • Substem A specifies the target of the antibody, such as a tumour or bacterial target Substem B specifies the sequence from which the monoclonal antibody was derived so, for example, antibodies that were derived from a mouse would contain the substem -o-. The suffix –mab is a common stem for all monoclonal antibodies. 14 6PY011 Musculoskeletal System 2 Study Pack 2025-26 Table 1: Monoclonal antibody substems and their respective targets or origins: Substem A -b(a)bacterial -c(i)cardiovascular -f(u)fungal -k(i)interleukin -l(i)immunomodulating -n(e)neural -s(o)bone toxin tox(a)-t(u)tumour -v(i)viral • • • Substem B A Rat Axo rat/mouse E Hamster I Primate O Mouse U Human Xi Chimeric Xizu chimeric/humanised Zu humanised This naming scheme may seem complicated, but it provides useful information about a monoclonal antibody. For example, consider the name for rituximab: o the prefix ri- is its individualised prefix. o the substem –tu- shows that it targets a tumour o the substem -xi- denotes that it is of chimeric origin and o the suffix -mab indicates that it is a monoclonal antibody Due to the association between biological DMARDs and various infections and conditions, pre-treatment screening is required to rule out the following: o Tuberculosis ▪ This will include a chest x-ray if a recent one is not available, to exclude signs of previous TB, as well as a Mantoux or Interferon-gamma release assay (IGRA) test ▪ Active or latent TB should be treated before starting a biological DMARD (see individual drug monographs in the current BNF for details). During treatment, patients should be advised to seek medical attention if symptoms suggest TB such as a persistent cough, weight loss and fever. Patients should also be counselled to seek medical attention if symptoms suggestive of blood disorders, such as fever, sore throat, bruising or bleeding develop. o Septicaemia o Hepatitis B – mab treatment can result in reactivation of the virus o Multiple sclerosis o Recurrent infection o Leg ulcers o History of cancer o Heart failure Routine blood tests are also required Task 8: What monitoring is required in patients treated with mAbs? 15 6PY011 Musculoskeletal System 2 Study Pack 2025-26 Targeted Synthetic DMARDs - Janus kinase inhibitors in RA • Low molecular weight, orally available, small molecules that target and inhibit components of the intracellular inflammatory signalling cascade have more recently been developed as an important alternative to biologic therapies for RA. • Many pro-inflammatory cytokines implicated in RA pathogenesis bind to a specific group of so-called Type I and Type II cytokine receptors, which are structurally distinct from other receptors such as those that bind TNF and IL-1. Cytokines binding the Type I and II receptors rely on the Janus kinase (JAK) family of enzymes for signal transduction. The JAK family comprises four members: JAK1, JAK2, JAK3 and TYK2. Drugs that inhibit the activity of these Janus kinases therefore block cytokine signalling. Several JAK inhibitors (jakinibs) with variable degrees of selectivity and specificity for the JAK enzymes have been investigated in RA. • To date, several JAK inhibitors have been approved for the treatment of RA: o Tofacitinib, a first-generation, selective oral JAK1, 3 inhibitor (with less activity against JAK2 and TYK2), has undergone extensive clinical trials of twice daily dosing in RA. o Baricitinib is a novel, potent and selective, first-generation, oral JAK1, 2 inhibitor (with moderate activity against TYK2 and significantly less activity against JAK3) that was generated by modifying the structure of tofacitinib. o Upadacitinib is an oral JAK1/3 inhibitor o Filgotinib is the most recent oral agent, which acts predominantly against JAK1. • NICE has published technology appraisals outlining the place of these agents in the management of patients with moderate to severe RA. Links to the NICE recommendations for each agent can be viewed using the following links: Baricitinib https://www.nice.org.uk/guidance/ta466/chapter/1-Recommendations Tofacitinib https://www.nice.org.uk/guidance/ta480/chapter/1-Recommendations Upadacitinib https://www.nice.org.uk/guidance/ta665/chapter/1-Recommendations Filgotinib https://www.nice.org.uk/guidance/ta676/chapter/1-Recommendations RA Complications • RA is known to be associated with an increased risk of infection, although it is difficult to distinguish the infection risk associated with the disease per se from the therapy-associated infection risk. o Corticosteroids, some DMARDs and targeted biologic therapies all have a negative impact on the capacity of RA patients to mount an adequate immune response and therefore superimpose additional infection risk to the intrinsically increased infection susceptibility of this patient population. Rheumatoid Arthritis in Children • • There are around 12,000 children under 16 in the UK with the juvenile form of the disease juvenile idiopathic arthritis (JIA), and although some children with JIA do not require DMARDs, methotrexate is an effective option. Sulfasalazine is an alternative but should be avoided in systemic-onset JIA. 16 6PY011 • Musculoskeletal System 2 Study Pack 2025-26 A number of biological DMARDs (abatacept, adalimumab, etanercept and tocilizumab) are currently recommended by NICE [TA373], as treatment options for JIA. Non-pharmacological Management • • • • Encourage regular exercise, particularly joint flexibility and muscle strengthening Physiotherapy – accessed via referral by medical team Occupational therapy – accessed via referral by medical team Podiatry – accessed via referral by medical team o Consider the need for therapeutic footwear and support Dietary Advice and the use of Complementary therapies in RA • NICE reviewed the evidence (three meta-analyses and 14 RCTs) on diet and dietary supplements in RA and concluded there was no consistent evidence of benefit (in terms of symptoms, joint damage, or function and quality of life) of any one particular diet. • However, NICE concluded that the principles of a Mediterranean diet (more bread, fruit, vegetables and fish; less meat; and replace butter and cheese with products based on vegetable and plant oils) could be encouraged if the person wishes to modify their diet, as people with RA are at an increased risk of cardiovascular disease compared with the general population. • Patients with RA who wish to try complementary therapies should be informed that although some may provide short-term symptomatic benefit, there is little or no evidence for their long-term efficacy. • Patients should also be advised that such therapies should not replace conventional treatment. However, NICE recommends that the decision to try complementary therapies should not prejudice the attitudes of members of the multidisciplinary team, or affect the care offered. Surgical Management • • Patients should be referred to a specialist surgeon in the following conditions, despite optimal non-surgical approaches: o If there is persistent pain o Deteriorating joint function o Worsening deformity o Persistent localised synovitis Patients experiencing the following complications should also be referred to a specialist surgeon: o Tendon rupture o Nerve compression o Stress fracture 17 6PY011 Musculoskeletal System 2 Study Pack 2025-26 Gout Diagnosis • • • • • Clinical history – joints affected, symptom onset and severity, frequency and duration of attacks, diet, drug history, medical history, family history Physical examination of affected joints Blood tests – serum urate levels Joint aspiration of synovial fluid X-ray of affected joint Differential diagnoses Gout may be mistaken for other conditions such as: • Osteoarthritis • Rheumatoid, psoriatic, septic or reactive arthritis • Trauma • Cellulitis • Haemochromatosis Pharmacological management • • • • The first attack/flare of gout is treated with a short course of either of the following oral drugs: o NSAID (excluding aspirin), colchicine or an oral corticosteroid ▪ NB corticosteroids are not licensed for use in acute flares of gout. ▪ A gastro-protective agent, such as a PPI should be considered in patients treated with an NSAID. The patient should be assessed in a follow-up to review the flare, possible contributing medicine use and repeat urate levels. For patients who experience several attacks of gout, or suffer with CKD stages 3-5, or have concomitant use of a thiazide-like diuretic, a urate-lowering therapy (ULT) should be considered, such as allopurinol and febuxostat. o These are usually lifelong treatments. o Treatment initiation should NOT commence during an acute attack but should commence several weeks after a flare has settled, unless the patient experiences frequent flares. o The dose is based on serum urate levels, as a treat-to-target strategy. For further information, refer to the NICE guidelines below: Overview | Gout: diagnosis and management | Guidance | NICE Non-pharmacological management • • • • Limiting alcohol intake – increased alcohol consumption can exacerbate a flare of gout. Weight management – excess body weight and obesity can exacerbate a flare of gout. Maintaining a balanced diet – there is insufficient evidence to support the use of a specific diet in managing gout. Ensuring adequate fluid intake. 18