Rheumatoid Arthritis

Question 1

Learning objectives

Answer 1

Recognise and identify signs and symptoms of RA

Explain how RA is diagnosed

Describe how the disease is monitored

Question 2

What are the symptoms of RA?

Answer 2

Differs from patient to patient

*1Insidious onset

*2fever, malaise, weakness

*3Symmetrical- inflammation- pain, tenderness, swelling, stiffness, redness and joint warmth. Stiffness for 30 mins before getting up or after resting, gelling effect difficulty to move joints.

*4Usually in the small synovial lined joints of the hands and wrist or feet

*5Can affect any joint

*6Progressive articulate deterioration- loss of function

*7Inflammation, destruction of bone and cartilage
*8Deformity, limited motion, pain on motion.

*9General symptoms- weight loss, fatigue, mental health changes

*10Extra articulation manifestations- lungs, heart, eyes, skin

*11RA nodules.

(Where we see patients with rheumatoid arthritis also at risk of things such as pulmonary fibrosis institutional lung disease for example it can affect the heart where increases a patient’s risk of cardiovascular disease patients with rheumatoid arthritis have a doubled increase of myocardial infraction their increased risk of congestive cardiac failure and of stroke it can affect the eyes in a condition called sjogren’s syndrome this is a condition where patients suffer with very dry eyes it can affect the skin and it can affect the bone as we’ll see increase in patients risk of osteoporosis around 20% of patients also suffer with RHI nodules these are firm lumps that appear subcutaneously around the joints such as the fingers the toes and the elbows and although the incidence of this is falling due to better treatment it is what we call a poor prognostic factor due to the fact that it means these patients have an increased severity of osteoporosis)

Question 3

What is the clinical course of the disease like in patients with rheumatoid arthritis? exacerbations and remissions

Answer 3

The clinical course of the disease is variable, with symptoms coming and going.

1- The disease is characterized by exacerbations (worsening of symptoms) and remissions (improvements in symptoms).

2- The severity of the disease can fluctuate over time, but it commonly results in chronic progression and deformities.

3- Flares can become more frequent and severe as the disease progresses.
- Some cases of the disease are self-limiting, while others are chronic.

5- Extra-articular manifestations (symptoms outside of the joints) increase the risk of cardiovascular disease.

6- Heart disease accounts for approximately 1/3 of deaths in rheumatoid arthritis.

7- Inflammation of blood vessels (vasculitis), changes to vessel function, clotting and cholesterol, and increased risk of infection and respiratory diseases contribute to the risk of cardiovascular disease.

8- Rheumatoid arthritis increases the risk of osteoporosis and certain types of cancer (e.g., lung and lymphoma).

9- Patients with more severe disease are likely to be on multiple drug therapies, which may contribute to these risks.

10- Appropriate treatment can help control inflammation, disease progression, and decrease the risk of extra-articular manifestations and associated comorbidities.

11- However, some treatments for rheumatoid arthritis may increase the risk of certain conditions (e.g., lung disease, certain types of cancer). For example methotrexate can increase a patient’s risk of lung disease and some of the anti-TNFs and some of the biologics can increase particular types of cancer so biologics there’s a link with non Melanoma skin cancer and also things such as infection as well as increased in patients that use biologics also so patient outcomes are compromised when treatment is inappropriate or delayed, because appropriate treatment can actually alter the course of the disease.

12- Patient outcomes are compromised when treatment is inappropriate or delayed.

The clinical course of the disease is very variable between patients especially in the beginning symptoms can come and go however generally the disease is characterised by exacerbations or flares where their symptoms are worsened and remissions which are improvements in their symptoms so the severity can fluctuate over time but most commonly results in chronic progression which leads to the deformities. So what we see happening is each flare not improving as much as it was previously leading to a general deterioration or general worsening of the condition and often these flares can occur more frequently and be more severe as the disease progresses saying that there are some cases although less likely that the disease is self limiting and some cases where it can occur chronically over a patient’s life would be intermittent so their symptoms improve in between each episode of the disease without that general big deterioration so the extra articular manifestations seen in those patients with a more severe disease can increase a patient’s risk of cardiovascular disease and actually heart disease accounts for around 1/3 of the deaths in rheumatoid arthritis now this is a really active area of research at the moment because there are multiple factors that are believed to play a role and these include things such as inflammation of the blood vessels so this is called vasculitis changes to the vessel function changes to the clotting and two cholesterol due to the inflammation it can increase a patient’s risk of infection it can increase a patient’s risk of respiratory diseases and this can account 10% of the death seen from RA it can increase a patient’s risk of osteoporosis and of malignancy so rates of some cancers are higher it’s not for all cancers so actually bowel cancer and breast cancer their rate is seen to be lower in patients with rheumatoid arthritis but there is an increased risk of lung and lymphoma and there’s also an increased risk of depression now because these patients have more severe disease increased number of symptoms they are likely to be on an increased number of drug therapies and it remains unclear as to whether drug therapy is also playing a role in some of these risks that we see so to control the inflammation and the disease progression if we can do that we can decrease the risk of developing these extra articular manifestations and also then the associated comorbidities that go alongside them however we need to be aware that some of the treatments that we use to treat the rheumatoid arthritis can increase the risk of similar conditions so for example methotrexate can increase a patient’s risk of lung disease and some of the anti TNFs and some of the biologics can increase particular types of cancer so biologics there’s a link with non Melanoma skin cancer and also things such as infection as well is increased in patients that use biologics also so patient outcomes are compromised when treatment is inappropriate or delayed so because appropriate treatment can actually alter the course of the disease other things we would want

Question 4

What tests are done to determine RA?

Answer 4

1. Blood tests are used to evaluate inflammatory markers and immunological parameters in patients with rheumatoid arthritis.
2. The erythrocyte sedimentation rate (ESR) is a measure of inflammation within the joints and increases within 24 to 48 hours of inflammation.
3. The ESR test involves placing blood in a solution and measuring the distance it falls within one hour. A faster fall indicates more inflammation.
4. An increased ESR indicates the presence of inflammation, although it is not specific to rheumatoid arthritis and can be elevated due to other conditions.
5. C-reactive protein (CRP) is a protein produced by the liver in response to inflammation. It starts to increase within 4 to 6 hours and peaks between 36 and 50 hours.
6. CRP can be increased for various reasons, not just related to joint inflammation, such as surgery, injury, or infection.
7. Rheumatoid factor is an autoantibody present in some patients with rheumatoid arthritis but not specific to the disease. Its presence can indicate more severe disease.
8. Anti-nuclear antibody (ANA) is an autoantibody present in approximately 40% of patients with rheumatoid arthritis and indicates increased disease severity.
9. Anti-cyclic citrullinated peptide (anti-CCP) is a more specific antibody for rheumatoid arthritis but not present in all patients.
10. X-rays can show joint damage and inflammation, but may not be conclusive in early disease.
11. Patients who test positive for rheumatoid factor or anti-CCP are termed “seropositive” and may have more severe disease, although individual courses of the disease can vary.
12. Limited motion, difficulty forming a tight fist, and pain or tenderness during joint squeezing tests are common symptoms observed during examination.
13. In addition to joint symptoms, extra-articular effects of rheumatoid arthritis in other areas of the body are also assessed during examination.

Test for inflammatory markers and immunological parameters.

Blood tests, So split into two groups we’re looking for inflammatory markers and looking also ask immunological parameters as well so one of those is we look at the emphasise sedimentation rate or the ESR it is a measure of the degree of inflammation within the joints and generally we get begin to see an increase in this within around about 24 to 48 hours of inflammation so erythrocytes segmentation rate is a blood test we’re going to take from patient

the process that happens then to carry out the test is the flood letter settle in a solution in a column over one hour and then we measure the distance that that blood has moved within the hour so a more rapid fall in that blood so the quicker it falls down the column indicates there’s more inflammation present and this is due to inflammation molecules being attached to the red blood cells causing clumping of which will increase the descend of the blood within the column so if we get an increase erythrocyte sedimentation rate it shows us that there is more inflammation present the thing to watch out here is that inflammation isn’t specific to joints it can be present because of other conditions that patient may have as well so it’s not specific to RA

C reactive protein or CRP this tells us about the degree of inflammation and it’s a protein that produced part of the innate immune response from the liver and it begins to increase in around about 4 to 6 hours after inflammation but can take some time to peak up to between 36 and 50 hours again CRP can be increased for a number of reasons not just related to joint inflammation so for example if a patient had surgery or an injury or infection both of these factors CRP and ESR may be increased that being said they are still used and they can be used to see whether there is general inflammation present and to monitor the patient over time

rheumatoid factor is something else that we would do a blood test for rheumatoid factor is that a type of autoantibody however 30% of patients with rheumatoid arthritis don’t actually have it present and there are other inflammatory conditions which can give a positive result for rheumatoid factor so although it’s called rheumatoid factor it’s not specific to rheumatoid arthritis and it is essential to a diagnosis of RA however the presence of rheumatoid factor is one of those poor prognostics factors and can indicate more severe disease

Anti nuclear antibody dy this is a type of auto antibody directed against components of the nucleus and this is a present in only approximately 40% of patients with rheumatoid arthritis however it is still tested for and again it is one of those factors which indicates an increase severity of disease and is a poor prognostic factor also anti cyclic citrullinated peptide anti-CCP this is more specific from rheumatoid arthritis than rheumatoid factor but not all rheumatoid arthritis patients have it this is also an antibody against the unusual amino acid citrulline which is formed when arginine is altered so unusual amino acid that’s present and again this is a sign of more severe disease if it is present we would also carry out tests or for patients haemoglobin to see if there were signs of anaemia this is quite common in RA and can correlate to disease activity

Testing through X-rays so radiology as this can show damage and inflammation present within the joint so you can begin to see if there are changes occurring within the actual joint space however in early disease this isn’t always visible on an X-ray so it may not be conclusive if it’s not present it may not be conclusive the patient doesn’t have RA just to say patients that get a positive result for rheumatoid factor or the anti CCP are termed O positive so you may see this written in the text and as I said zero positive patients this is a general indicator that they have more severe disease but everyone is different and their course of the disease may be different as well

other things that we would see in patients when we think about their diagnosis is that they would have limited motion so patient forming a fist it would be difficult for them to form a very tight fist so that maybe because of pain or stiffness metacarpophalangeal or metatarsophalangeal for the feet squeeze

Squeeze across the knuckle joints of the hand or the foot now if your to do that there is some movement but I wouldn’t say exactly squeegee the squeeze test if a patient has RA often you will feel some jelling since it feels a bit like a gel within those joints this is really very painful for the patients so cause extreme pain or there is a lot of tenderness within those joints so when a patient is examined they want to recognise the symptoms as we’ve already discussed so we wanted to see whether the patient has stiffness or tenderness or pain or motion whether they have swelling or deformity within those joints that can be seen already but we would also be looking for any extra articular effects whether it’s having effect on other areas in patients body

Question 5

How do we diagnose RA?

Answer 5

No one test will provide a diagnosis
Dependent on complete history taking, clinical presentation and investigation.

Morning stiffness for greater than
30-mins stiffness after quiescence family history lifestyle.

Symmetrical effects on synovial joints symptoms as discussed.

Inflammatory markers haematological parameters
Immunological parameters
Radiological investigations

• No specific test for diagnosis; disease varies among patients
• Multiple potential differential diagnoses for arthralgia (joint pain)
  
  • Fibromyalgia
  • Polymyalgia rheumatica
  • Osteoarthritis
• Diagnosis of RA relies on comprehensive patient history
  
  • Morning stiffness
  • Family history
  • Lifestyle factors
  • Environmental triggers
  • Medical history of predisposing conditions (e.g., psoriasis)
• Assessment of clinical presentation
  
  • Symmetrical joint involvement
  • Affecting synovial-lined joints
• Investigation includes:
  
  • Inflammatory markers
  • Hematological markers
  • Immunological parameters
  • Radiological investigations

There is not one single test that can be done which will tell us patient has RA or not and it’s dependent on the doctor gathering a complete history from the patient so we need to know whether they are suffering with morning stiffness or stiffness after they rested which which last for between 30 and 45 minutes after getting up whether there is a positive family history for the disease whether they do have lifestyle factors which put them at increased risk or have come into contact with environmental triggers that could have triggered arthritis whether they have in their medical history other conditions which could predispose them to certain types of rheumatoid arthritis so if they had psoriasis for example we’re also going to be looking at the clinical presentation so whether it’s affecting joints symmetrically whether it’s affecting synovial line joints also the doctors will look at the investigation so they’re going to look for those inflammatory markers haematological markers on the immunological parameters as well as looking at radiological investigations so it becomes a whole host of things that need to be investigated that the rheumatologist will look at before they can say whether the patient does or doesn’t have rheumatoid arthritis

Question 6

How to diagnose RA?

Answer 6

• NICE guidance for RA N G100 (2018) emphasizes referral to rheumatologists for better outcomes.
• Urgent referral is necessary for patients with persistent sinusitis affecting multiple joints or delayed medical advice.
• Delayed diagnosis and treatment worsen outcomes and affect joint function.
• Diagnosis involves clinical examination for synovitis, blood tests for RF, and consideration of anti-CCP antibodies.
• X-rays of hands and feet are recommended if necessary.
• Additional investigations are conducted based on initial findings.
• Positive RF results negate the need for anti-CCP antibody testing.
• Health assessment questionnaires evaluate functional ability and quality of life.
• Questionnaires cover disability, discomfort, pain, drug side effects, toxicity, and treatment costs.

NICE guidance for RA NG100 published back in 2018 so this tells us about referral so as you can imagine many patients go to their GP and primary care with their symptoms however it is known that patient outcomes are improved when the patient is managed by a specialist within the area so a rheumatologist so the NICE guidance tells us that primary care should refer to specialist care any patients suspected persistent sinusitis so that inflammation of the joints

this referral should be done urgently if it’s affecting this more joints of the hands and feet more than one joint or if the patients delayed seeking medical advice because it’s known that the later the diagnosis and effective treatment is started the worse the outcome is for the patient in so much that it’s harder to control and that the patient will begin to potentially begin to see some of those changes within the joints which will bring about changes with their ability to use those joints

so in terms of diagnosisNICE suggest that so patients if they are found to have synovitis on clinical examination which we’ve already discussed we should do be doing blood tests to test for RF and that we should consider doing a blood test for anti-CCP antibodies if the rheumatoid factor blood test is negative we should also be carrying out X-rays off the hands and feet

so basically this is stating that we need to look at many different areas as I discussed on the previous slide to be able to give the patient a diagnosis of with this or not there are some

additional investigations that are done so if for example the RF comes back positive which would indicate we don’t need to test for anti-ccp to make our diagnosis we would then do any outstanding blood tests etc that haven’t been done so that we’ve got a baseline information about the patient

plus we also get patients to fill in a health assessment questionnaire and that tells us about the patients functional ability so it was developed as a comprehensive measure of the outcome in patients with rheumatoid disease and it concentrates on self reported patient orientated outcome measures so it looks at disability discomfort and pain drug side effects and toxicity once we get to treatment and also costs so it covers functional status as well as the patients quality of life

Question 7

How to monitor RA progression?

Answer 7

• Monitoring disease progression is crucial for understanding baseline status and assessing treatment efficacy.
• Disease activity is measured using the DAS 28, which evaluates 28 joints for swelling and tenderness, along with ESR or CRP levels and a global health assessment.
• DAS 28 scores categorize disease activity as active, low, or in remission, guiding treatment decisions.
• Scores above 5.1 indicate active disease, below 3.2 suggest low disease activity, and below 2.6 signify remission.
• DAS 28 scores also determine eligibility for specific drug treatments like biological agents.
• Interpretation pitfalls include exclusion of certain affected joints, like those in the feet, and variability in ESR levels.
• Despite its use, individual patient specifics must be considered alongside DAS 28 scores for accurate assessment.

Monitoring a patient’s disease is important both at baseline so that we get an understanding of where the patient is when we first see them to show how interventions are or are not improving the situation but also to guide where we go next what next steps can be taken and you’ll see when we move onto the management of RA that actually the scores that will get from our monitoring help decide whether a patient should move on to particular therapies so when we’re monitoring disease we use something called the DAS 28 so this is a measure of disease activity and the 28 stands for 28 joints and they are shown in the diagram so there are four different measures that go into this score so the number of swollen joints so we’d assess whether how many out of the 28 swollen the number of tender joints would also do a measure of their ESR or CRP so and we also have a look at a global assessment of health score so this asked for the patient to provide an overall score of disease activity

so the score once calculated will indicate whether we’ve got patient with active disease low disease or remission so if the score is greater than 5.1 we’ve got active disease
less than 3.2 we’ve got low disease activity
and less than 2.6 we’ve actually got mission and this allows us to monitor the disease and also whether the treatments that we’re giving are improving the situation and also as a criteria for eligibility for certain drug treatments such as the biological agents

there are pitfalls to its interpretation for example if patients have joints affected within their feet for example you see that on the diagram they are not included in the 28 joints that we look at

also some patients don’t see that characteristic increase in their ESR so by including that into the score would show that this patient has a lower score overall than actually their disease is showing so it is important that although this is used that we’re also looking at the specifics of each of our individual patients

Question 8

How to manage RA?

Answer 8

• Management of RA involves early therapy to improve symptoms, function, and reduce mortality and comorbidities.
• Treatment is not solely pharmacological; a multidisciplinary team including physiotherapists and occupational therapists plays a vital role.
• Physiotherapists and occupational therapists aid in daily life activities, provide exercises, and offer specific therapies.
• Orthotics may be recommended to assist patients in daily activities.
• In severe cases, surgery may be necessary to enhance functional ability and improve quality of life.
• Overall, RA treatment requires a comprehensive multidisciplinary approach.

The management and we’re going to be looking at the management as described in two different guidelines so we’re going to be looking at the nice guidance and the EULAR guidance European league against rheumatism guidance so with management we need to have appropriate early therapy this improves patient symptoms improves patients function reduces mortality and can reduce patients comorbidities as well just a note that treatment is not always pharmacological an actually there is a large multidisciplinary team that will be looking after patients that are diagnosed with RA this can include physiotherapists occupational therapists who will be thinking about ways in which we can help the patient with the activities of daily life in terms of the occupational therapy or whether there are exercises that can help a patient with RA or particular therapies that physio can provide that can help there may be things like orthotics that can help the patients carry out their activities of daily life and we mustn’t forget that some patients if they do progress to very severe disease the only way in which we can improve that patients quality of life can be surgery so we might have to operate on a patient’s joints to improve their functional ability
so it’s a big multidisciplinary team approach to the treatment of a patient with RA.

Question 9

Learning objectives treatment of RA

Answer 9

Learning objectives by the end of this screencast you should be able to describe and apply appropriate guidelines for the management of rheumatoid arthritis

Question 10

What are the aims of the treatment?

Answer 10

The aims of treatment are to minimise the patients joint pain and swelling prevent deformity and radiological damage such as erosion.

Delay the progression of the disease maintain a patient’s quality of life prevent or control extra articular manifestations all of this relies on fast and effective diagnosis and treatment.

The treatment process is an active one it is not the case of giving the patient a drug and leaving them on it it requires close monitoring of the drug and potential dose or drug adjustments to keep control of the patient’s disease.

Question 11

What are the treatment guidelines?

Answer 11

The guidelines that we will be used are the NICE guidance rheumatoid arthritis in adults management NG100 and for additional detail will be looking at the European league against rheumatism guidance EULAR.

The reference for the EULAR guidance has been updated in the handouts (but not in the screencast), to include the 2023 update.

Question 12

Give the overall treatment of RA?

Answer 12

The main treatments used in RA must start with symptom control you see analgesia is used and the analgesic of choice is a non steroidal anti-inflammatory this shows a small benefit in relieving patient symptoms including pain and stiffness. there is limited evidence for other types of analgesia such as paracetamol compound analgesia opiates etc therefore these are not recommended under the NICE guidance however you may still see patients on other types of analgesia for rheumatoid arthritis pain.

Glucocorticoids are another drug class that are used for the treatment of rheumatoid arthritis they reduce inflammation and pain they can be given systemically either orally or parenterally or they can be given locally intraarticularly into a joint they’re used at multiple levels during treatment so for example they may be used when another drug treatment is being started or they can be used if a patient suffers with a flare in their rheumatoid arthritis.

The mainstay of rheumatoid arthritis treatment are the DMARDs the disease modifying antirheumatic drugs as the name suggests these control the underlying disease so the underlying pathophysiology of rheumatoid arthritis the main goal of treatment with these drugs is to get remission for the patient

1- the conventional DMARDs cDMARDs these are the therapies that patients start their therapy on and drugs in this group include methotrexate sulfasalazine and leflunomide hydroxychloroquine is also discussed in the NICE guidance but is only used for certain types of rheumatoid arthritis you may also see if you look in other literature other drugs being named and these are no longer used as frequently for the treatment of rheumatoid arthritis as they were in the past and these may include azathiporine, penicillamine gold cyclosporin

2-the biological DMARDs and there are different groups of these so we have the anti TNF agents such as adalimumab, etanercept, certolizumab, golimumab, infliximab and other biological agents such as tocilizumab/ sarilumab which are both interleukin 6 receptor inhibitors

Rituximab which is an anti B cell (anti-CD20 antibody)

Abatacept which is an antibody blocking T cell T lymphocyte activation so costimulation modulator

3- The targeted DMARDs and these act on the Jack stacked pathway and so these are called the Jack inhibitors and in this group we have tofacitinib, baricitinib, upadacitinib, filgotinib.

Question 13

What’s the NICE treat to target consists of and what factors are taken into consideration?

Answer 13

The NICE NG100 guidance it’s important to understand the underlying strategy used in the guideline for treatment of rheumatoid arthritis and so that’s where we’ll start

each patient treated for RA will have a specific treatment target and their treatment will be monitored and modified with new strategies being implemented based on the monitoring to achieve their specific targets and we call this treat to target it relies on frequent reviews of both their disease and their treatment, formal assessment of their joints and escalation of their therapy if the inflammation is still present i.e is not being controlled until that control is reached

patients have an individual target and for most patients this is remission so a DAS 28 score of less than 2.6 and for a few patients this maybe slightly higher where we wanted to achieve low disease activity and a DAS score of less than 3.2
what we’re seeing here is tight control of a patient’s rheumatoid arthritis and it’s believed that tight control is what gives the favourable outcomes of treatment so in terms of monitoring a patient will have their blood tests monitored so for example their ESR & CRP will have their DAS disease state activity monitored and this will be done on at least a monthly basis in a specialist care setting with a rheumatologist until their target was reached
and during this monitoring rheumatologist will be reviewing how well they’re achieving their target with potentially implementing changes to their treatment to reach that target

Question 14

What is the initial treatment of RA in NICE guidance?

Answer 14

Initial treatment of a newly diagnosed active RA patients first line therapy are conventional DMARDs and these should be used as monotherapy there is no evidence to suggest that starting with more than 1 DMARD is any more efficacious and actually may increase the potential for adverse effects of those drugs. treatment should be started as soon as possible and ideally within three months of the onset of symptoms the sooner patient starts the more likely they are to get a response from their conventional DMARD and the less likely they are to see deterioration in their symptoms.
so the recommended options for initial first line treatments are oral methotrexate or oral Leflunomide and oral sulfasalazine and for completeness I have added in here just to show you where hydroxychloroquine sits it is recommended as a first line treatment potentially for mild or palindromic rheumatoid arthritis disease and not for more severe cases as it is less effective than the first 3

as you can see one cDMARD is not picked out over another there is no consistent difference in the effectiveness of the monotherapy just add an extra little note in here and although not recommended by nice due to its cost subcutaneous methotrexate you may see it being used in practise sometimes if patients haven’t responded as well to oral methotrexate as expected so it’s considered as a failure or if a patient is suffering from problematic gastrointestinal side effects with oral methotrexate, some rheumatologist will switch patients to subcutaneous methotrexate in practise and this can be significantly more effective than the oral treatments without an increase in potential adverse effects its use can also then prevent having to add in additional treatments so that is something you may see in practise

when rheumatologists make the decision about which treatment a patient should be started on they will do so based on the characteristics of the drugs so the cautions contradiction side effects etc the drug and also the patients characteristics regarding other medical conditions they have other drug therapies they’re receiving you do however still see lots of methotrexate being used first line rheumatologists have lots of experience of using this drug is being used for really long time in rheumatoid arthritis and also it is a drug that can have other therapies added to it which we’ll see later on

one started on therapy patients will have their doses escalated up to effective treatment dosage for rheumatoid arthritis however this does sometimes become a balancing act between getting up to an efficacious dose and also potential adverse effects that the drug causes so this will be considered by the rheumatologist at the time of them being reviewed the patient being reviewed and it may well be that the patient either has to do the escalation more slowly or they have to stay at certain dose because higher doses cause them adverse effect

as you know all cDMARDs take time to have their therapeutic effect or their full therapeutic effect during this time patients will still be experiencing symptoms and potentially adverse effects as well which can lead to patients discontinuing their therapy an so to manage this patients could be offered bridging therapy with glucocorticoid so this may be considered for patients this is where the patient is given a short course of steroids when starting their cDMARDs and what we do with short courses aiming to have it removed as soon as possible but generally by three months and the patients benefit from the anti-inflammatory effects of the steroids this gives us the bridge to when their conventional DMARD is fully active this may be particularly important for patients with more active disease because getting some relief from that active disease and some control of the inflammation is really important but may not be needed for patients with less active disease so it’s considered on a case by case basis now currently there is a lot of variation in the drug that’s used the corticosteroids that is used and also the corticosteroids dose that used and NICE has made a research recommendation determine the effectiveness of corticosteroids as a bridging therapy but also the best strategy for the best dose the best drug that should be used so for examples that you might see used oral Prednisolone 7.5mg or 10mg today up to 30 milligrammes a day you might see methylPrednisolone intravenously intramuscularly intraarticulary120 milligrammes weekly on different weeks.
you might see triamcinolone intramuscular or intra articular.

Question 15

What is the NICE step up strategy?

Answer 15

In the treat to target strategy we are monitoring the patient we’re aiming for disease remission and if we don’t get that effect we want with our conventional DMARD monotherapy even once it’s been optimised this is when we bring in a step-up strategy and NICE recommends that we offer an additional conventional DMARDs so either methotrexate Leflunomide sulfasalzine, hydroxychloroquine that’s not currently being used, being added onto the conventional team of the patient was initially on in mono-therapy.

This should give better control and hopefully target achievement but it may also increase the risk of adverse effects and will require more intensive monitoring than monotherapy especially as lots of the agents and have similar adverse effects and so these can make the effect worse.

Question 16

What procedure is taken if step-up strategy fails?

Answer 16

• If mono-therapy fails, escalate to step-up strategy
• Consider other therapies for target not achieved
• NICE technology appraisals recommend treatments
• Treatments for moderate disease: Anti-TNF agents, targeted DMARDs
• Treatments for severe disease: More choices including different agents
• Licensing and use with methotrexate indicated, some exceptions
• Specialized team manages these drugs in trusts
• Consider patient characteristics, other conditions for therapy choice
• Consider delivery route, storage, adverse effects in drug selection
• Dose, frequency, comorbidities influence agent choice
• Patient allergies, individual needs impact drug selection

Offer additional DMARDs

If we have used a mono-therapy and that has been escalated and not bought about the target that we require we have used the step up strategy so we’ve added in a second conventional DMARD and escalated that therapy and we still don’t get the target that we require then we have the potential to consider other therapies that can be used and there are a number of NICE technology appraisals which recommend different treatments if this is the situation and these can be split into treatments used for moderate disease and those used for severe disease and I’ve added the DAS 28 scores for moderate and severe at the top of the table now this table summarises the technology appraisals for you generally what we’re talking about here is when a patient has had two or more conventional DMARDs which have failed to bring about the target that they are aiming for and you may sometimes see some of these agents being used if for example the patient can’t have those conventional DMARDs or have reactions to them etc so you may see them used at different points then but in terms of what we’re discussing here in the flow of things we’ve got the monotherapy escalation, the step up therapy the escalation and then the potential for these therapies to then be used and if you look at the therapies we’ve got here we’ve got the anti-TNFs we’ve got the targeted DMARD and then we have the other biological agents.

The treatments available for moderate disease we have the anti-TNF agents adalimumab, Etanercept and infliximab now these are relatively new addition to treatment for moderate RA following a technology appraisal back in 2021 we also have certain targeted DMARDs filgotinib and upadacitinib and also antibody blocking T cell activation Abatacept and that should say CD8-/86 as these are what is bound by the antibody so you’ll notice there’s no anti IL-6 and no anti B-cell antibodies that are used in moderate disease

whereas in severe disease there is a lot more choices, so you’ve got the addition of the anti TNF agents certolizumab and Golimumab but also some of the targeted DMARDs such as baricitinib, tofacitinib, the anti IL 6. sarilumab and tocilizumab and also the anti- B cell Rituximab.

in the table as well that most of these agents are licenced and should be used with methotrexate as well and that’s denoted by their plus methotrexate but you also see for some of them there’s also a minus there as well and that means that for example if the patient couldn’t take methotrexate that agent could be used without methotrexate if you were to look any of these agents up in the BNF on the SPC for example you may well find that they have licencing for both moderate and severe disease but you are only seeing them on this table or one of those and this happens where the guidance is for either moderate or severe generally this is based on cost and whether there is evidence that this agent is better or worse than another agent that’s being currently being used

this is a specialised area of pharmacy and often within trusts that use a lot of these agents and there will be a dedicated team or pharmacist and a technician or a team of people more than just the pharmacist and the technician who look after these drugs and also ensure that the correct pathways are set up for being paid for the treatment and also for the patients receiving the treatment as some of these agents if they are given for example by subcutaneous injection can be given by the patient themselves to themselves and often what happens is the supply chain will be set up so that these patients are on what we call home care and the supply of medication goes straight to the person’s home it doesn’t come via the hospital so that they can then administer as they need to

as with the other DMARDs that we’ve discussed the choice of therapy will be additionally based on their patients characteristics, other conditions they have other, medications that they’re taking but also the drug characteristics as well and often there’s quite a bit of local guidance to help prescribers when making these choices if there is no clear indication for use of a specific agent then the most cost effective one should be used and we should be considering
staff time and site time as well so for example if you were using an intravenous therapy that would have to be done in the hospital setting using nursing staff time and also bed time and whereas if a patient can you somethings subcutaneously they don’t have to come into hospital they don’t have to then rely on that nurse as well so she’s going to provide you with a few examples why you may choose one agent over another so we’ve already talked about the fact that subcutaneous could free up bed spaces free up nursing time

however if we have a patient whose adherence isn’t very good or someone who has manual dexterity issues who couldn’t give subcutaneous injections then we might want to have them using IV therapy or coming into hospital to have that done

The delivery route can be quite important with most of these agents they are given as some form of injection but you’ve got your targeted therapies your tDMARDs these are actually oral therapies so they might be first consideration when we’re considering patient with manual dexterity issues or with a needle phobia for example we’ve got storage to think about as well most of the agents most of the biologics need to be stored in a fridge but our targeted DMARDs are oral therapies that don’t need to be stored in the fridge so that might be a consideration we need to be thinking for example about the adverse effects of the drug so you’re are targeted DMARDs are not going to have an injection site reaction because they’re oral therapies however lots of the injectable agents could lead to injection site reactions and

we would look at drugs risk of causing certain side effects so for example tocilizumab or sarilumab can increase the risk of GI perforation so we wouldn’t want to give that to a patient at risk of or with a history of gastric ulceration

similarly some agents have increased risk of. venous thromboembolism that targeted DMARDs therefore we wouldn’t want to give these to patients with increased risk of venous thromboembolism

We may also consider the dose and frequency of agents so for example some agents can be used less frequently such as filgotinib we may also consider our patients other comorbidities if for example they had conditions where certain ones of these drugs were also indicated we could end up using one drug to treat two conditions reducing obviously patients risk of adverse effects cost etc so for example golimumab is licensed for UC but also RA and similarly Adalimumab is licensed for RA as well UC and Crohn’s or for example a patients comorbidity may mean that we shouldn’t be using a certain agent so for example if the patient had severe heart failure then we wouldn’t want to be using the anti-TNF agent

we may also consider a patient allergy so for example just as an example of this if a patient had an allergy to latex some of these agents will contain latex within their manufacturing process within their containers but there is the biosimilar of Etanercept which is actually latex free so you can see how the drug treatment choice would be very dependent on the individual patient that we were treating.

AI:

• Treatment escalation strategies may involve mono-therapy, step-up therapy, or consideration of alternative therapies.
• If mono-therapy fails to achieve target remission, step-up therapy involves adding a second conventional DMARD.
• If target remission is still not attained, alternative therapies may be considered based on NICE technology appraisals.
• Treatments for moderate RA include anti-TNF agents (adalimumab, etanercept, infliximab), targeted DMARDs (filgotinib, upadacitinib), and antibody blocking T cell activation (abatacept).
• Treatments for severe RA offer a wider range of options, including additional anti-TNF agents (certolizumab, golimumab), targeted DMARDs (baricitinib, tofacitinib), anti-IL 6 agents (sarilumab, tocilizumab), and anti-B cell agent (rituximab).
• Most agents should be used with methotrexate, denoted as “plus methotrexate,” but some can be used without methotrexate, indicated by “minus.”
• Treatment choice depends on patient characteristics, comorbidities, drug characteristics, and local guidance.
• Route of administration (oral vs. injection), storage requirements, adverse effects, and drug interactions are important considerations.
• Dosing frequency, potential for adverse effects, and suitability for patient’s other conditions influence treatment selection.
• Patient allergies, such as latex allergy, may impact drug choice, with alternatives available in some cases.
• Overall, treatment decisions are individualized based on patient-specific factors and treatment goals.

Question 17

What are the targets for moderate and severe RA to continue treatment for patient?

Answer 17

As with all drugs and specifically in RA with our treat to target strategy these treatments will also have their effectiveness monitored and this will be done using the European league against rheumatism criteria at six months

they must show a moderate response to the treatment that they have been given and this moderate response is indicated by a particular DAS score and a moderate response for patients with moderate disease is different from a moderate response for patient with severe disease which will see now

so for those with moderate disease they must have a moderate response which is a DAS score of greater than 0.6 and less than 1.2 at 6 months to be able to continue their therapy

whereas if a patient has severe disease they must also have a moderate response but their DAS score must be greater than 1.2 response to be able to continue their therapy

I just want to say that treatment options after failure of biological or targeted DMARDs are not considered in this screencast you are not going to be expected to say what treatment options you should be using after these therapies have failed

Question 18

What happens if remission is maintained for 1yr?

Answer 18

• Achieving target remission for at least a year without corticosteroids may prompt consideration of a step-down therapy.
• Step-down strategy involves cautiously reducing drug doses or stopping certain medications based on patient’s therapy regimen.
• Reduction or cessation of therapy depends on patient’s response and absence of flares.
• Patients must be educated about recognizing signs and symptoms of flare-ups and how to contact the rheumatology department, often through a specialist nurse.
• Flares may be treated with corticosteroids before returning to previous DMARD regime or adjusting doses.
• Symptom control includes the use of NSAIDs and COX-2 selective inhibitors if pain and stiffness are inadequately controlled, considering potential toxicities.
• NSAIDs should be prescribed at the lowest effective dose for the shortest duration, with concurrent proton pump inhibitor (PPI) use to protect the gastrointestinal tract.
• Treatment should be regularly reviewed, considering patient’s risk factors such as cardiovascular disease (CVD) risk.
• Symptom control strategies are typically short-term, as the focus is on appropriate DMARD therapy to achieve target remission and pain/stiffness control.

*If we have provided the patient with the therapies that they require to get them to their target remission and if this is maintained for at least a year without the need for using corticosteroids and we would use these for example if the patient has a flare in their disease so if they haven’t used the corticosteroids then we may consider step down therapy or step down strategy this is where we consider cautiously reducing drug doses or stopping certain drugs so it depends on how many therapies the patient is on but it may well be that we can step down doses and as long as the patient doesn’t come up with any flares we may be able to remove a certain drug for patients or more than one or it may well be that we can step down their therapy just in terms of the doses that they’re needing to receive however this can be associated with flare ups and so patients need to have access to the rheumatology department and know what they should do if they begin to suffer with flare ups they must know the signs and symptoms that they are suffering and know to contact the rheumatology department often a specialist nurse in that department

what happens then is if they all suffering with a flare they probably be given a course of corticosteroid to help bring that under control but they will return to previous DMARD regime that was known to achieve the target that they were looking for
increasing that dose up to where we know the patient was well controlled or it may be that we had to add in another agent and agent the patients already being on that we know brings them good control

symptom control: evidence for everything except NSAIDs is pretty spars but you do sometimes see other analgesics used

NICE recommends and what you see in most patients is the use of traditional NSAIDs and COX-2 selective inhibitors when the control of pain and stiffness is inadequate again it’s important to be considering which is the most appropriate to start your on patient due to the potential toxicities that NSAIDs have

we want to ensure that we are using the lowest effective dose for the shortest time that we’re offering the patient of PPI to protect their gastrointestinal tracts and that we’re reviewing the treatment very regularly and that we’re reviewing the patient for risk factors associated with NSAIDs so CVD risk for example

we would expect symptom control strategies to be quite short term as the patient should be on an appropriate DMARD therapy which is getting them to their targets and their target will include control of their pain and stiffness so these are just a potential additional agent that would be used if the patient had inadequate pain control or was suffering with stiffness.

Question 19

How do we manage flare ups of RA?

Answer 19

The management of flares so this is where the patient’s condition quickly deteriorates and their symptoms get worse

For the most patient treatment of a flare consists of short term glucocorticoids which rapidly reduce the inflammation so the short term therapy should be stopped it’s not something that continues long term the only reason you may see this continue long term is for a patient who has exhausted all other treatment options all other treatments have been offered and the patient is well aware of the potential issues associated with long term use of glucocorticoids and this is quite a rare occurrence for a patient to be on glucocorticoids for long term control

Question 20

What monitoring is done for patients on treatment of RA?

Answer 20

Monitoring patients will be under the care of a rheumatologist and they will be provided with information on how and when to access specialist care so for example a specialist nurse who they might be able to speak to in relation to symptoms they’re experiencing or issues with their medication and also this enables them to have rapid access to a rheumatologist if they suffer up with a flare get the treatment that they require and also the fact that they will be having ongoing drug monitoring as well as disease monitoring to ensure that their drugs aren’t causing them any adverse effects or any issues or that their patients risk factors have changed and so the drug would then not be as appropriate for them or need dose adjustments

so once stabilised a patient should be reviewed every six months after they’ve achieved their target and to ensure that they are being maintained at that target if they’re not being maintained that’s when their monitoring increases but also we make changes to their therapies to try and achieve the target

all patients should also have an annual review which assesses their disease activity their damage and functional ability using the HAQ questionnaire they at this check we should also be checking for the development of any comorbidities that the patient might now have which again as I said might make one drug is now no longer appropriate for them
this is where for example we might get organisational cross referrals to others within the MDT so such as the physio occupational therapist, dietitian etc and also it will assess the effect on patients personal life as well because of the treatments that patients are receiving and the fact that rheumatoid arthritis itself increases risks patients should will be directed to have the seasonal flu injection and we also have the pneumococcal injection prior to starting therapy

Question 21

What does the EULAR state for the management of RA? Phase-1,2,3?

Answer 21

The EULAR guidance for RA there are many similarities to the NICE guidance so use of the best care, making shared care decisions ensuring that it’s under the care of a rheumatologist and that the treatments is based on the patient’s disease and their characteristics as well as the drug characteristics that we’re treating to target we having regular monitoring and we start therapy as soon as possible

EULAR states that the first line treatment therapy should be with methotrexate unlike NICE which has the three options EULAR recommends methotrexate as the first line

however it does recommend it as monotherapy and it should be escalated a quick escalation 4-6 weeks to effective doses which are best known to control RA again this is monotherapy so we’re not seeing it used in combination with other DMARDs

what to do if patients have contraindications o methotrexate we can use Leflunomide or sulfasalzine and also the option for bridging therapy with glucocorticoid also

now the recommendation for review here is a relatively short period of time so if improvement is at 3 months is seen and that the patient’s target is reached at six months then they should remain on their current therapy and then have the potential to reduce doses if that maintenance of the patient’s remission is achieved if not the patient moves on to phase-2 and this is where EULAR differs from NICE because it considers specific factors about the patients and they call these poor prognostic factors so if the patient has any of these presents they feel that they should be stratified here to have different therapy to patients who didn’t have these factors presence

so poor prognostic factors could be persistent moderate or high disease even with the conventional DMARDs increased acute phase reactants CRP and ESR increase number of joints affected the presence of rheumatoid factor or ACPA these autoantibodies if the patient has earlier erosion or if they’ve had failure of two or more drugs

for these patients their RA thought to be more severe and more progressive and this is why they are put down a different route so end up with slightly different therapies so here if you were a patient with poor prognostic factors it would be a case of adding a biological DMARD or adding a Jack inhibitor

if you didn’t have the poor prognostic factors then it would be a change so again this is different to NICE this will be a change in the DMARDs that you will be using or the addition of a conventional DMARDs

further reviews then we’re hoping to see improvement at 3 months and target achievement at 6 months to maintain the therapy if you don’t maintain the therapy, phase-3 must be considered but you are not expected to know what to do if phase-2 fails

Question 22

What is considered in deciding initial phase of RA therapy?

Answer 22

Patient preference
Patient characteristics
Co-morbidities
Risk factors
Treatment characteristics
Cautions, contraindications, side effects, dosing, interactions, and monitoring requirements

so appropriate type control manages the underlying pathology but also the occurrence of flares so it’s important to make sure that the patient ends up on the correct drug to control their disease

It’s important that this is based on patient preference to have that shared decision making process but also on the patients characteristic their comorbidities risk factors for example as well as the treatments characteristics so it cautions, contraindications, side effects, interactions etc you should now be able to describe and apply appropriate guidelines to the management of patients with RA.