Rheumatoid Arthritis Flashcards
Investigations for diagnosis
Offer to carry out a blood test for rheumatoid factor in adults with suspected rheumatoid arthritis (RA) who are found to have synovitis on clinical examination.
Consider measuring anti-CCP antibodies in adults with suspected RA if they are negative for rheumatoid factor.
X-ray the hands and feet in adults with suspected RA and persistent synovitis.
Investigations following diagnosis
measure anti-CCP antibodies, unless already measured to inform diagnosis
X-ray the hands and feet to establish whether erosions are present, unless X-rays were performed to inform diagnosis
measure functional ability using, for example, the Health Assessment Questionnaire (HAQ), to provide a baseline for assessing the functional response to treatment
Initial pharmacological management for adults with newly diagnosed active RA:
Offer first-line treatment with conventional disease-modifying anti-rheumatic drug (cDMARD) monotherapy using oral methotrexate, leflunomide or sulfasalazine as soon as possible and ideally within 3 months of onset of persistent symptoms.
Consider hydroxychloroquine for first-line treatment as an alternative to oral methotrexate, leflunomide or sulfasalazine for mild or palindromic disease.
Escalate dose as tolerated.
Consider short-term bridging treatment with glucocorticoids (oral, intramuscular or intra-articular) when starting a new cDMARD.
Offer additional cDMARDs (oral methotrexate, leflunomide, sulfasalazine or hydroxychloroquine) in combination in a step-up strategy when the treatment target (remission or low disease activity) has not been achieved despite dose escalation
Further pharmacological treatment
Biological and targeted synthetic DMARDs
On the balance of its clinical benefits and cost effectiveness, anakinra is not recommended for the treatment of RA, except in the context of a controlled, long-term clinical study.
Do not offer the combination of tumour necrosis factor-α (TNF-α) inhibitor therapy and anakinra for RA.
Glucocorticoids
Offer short-term treatment with glucocorticoids for managing flares in adults with recent-onset or established disease to rapidly decrease inflammation.
In adults with established RA, only continue long-term treatment with glucocorticoids 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
Symptom control
NSAIDs when control of pain or stiffness is inadequate
When treating symptoms of RA with oral NSAIDs:
- offer the lowest effective dose for the shortest possible time
- offer a proton pump inhibitor (PPI), and
- review risk factors for adverse events regularly.
If patient taking low-dose aspirin consider alternatives before adding NSAIDs if pain relief insufficient.
Bridging treatment
Glucocorticoids 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).
Conventional disease-modifying anti-rheumatic drug (cDMARD)
Conventional disease-modifying anti-rheumatic drugs are synthetic drugs that modify disease rather than just alleviating symptoms. They include methotrexate, sulfasalazine, leflunomide and hydroxychloroquine, but do not include biological DMARDs and targeted synthetic DMARDs.
Treat-to-target
A treat-to-target strategy is a strategy that defines a treatment target (such as remission or low disease activity) and applies tight control (for example, monthly visits and respective treatment adjustment) to reach this target. The treatment strategy often follows a protocol for treatment adaptations depending on the disease activity level and degree of response to treatment.
csDMARD choices include
methotrexate, hydroxychloroquine, sulfasalazine and leflunomide.
Sulfasalazine
Sulfasalazine (enteric-coated) is indicated in mild-tomoderate disease. It has an onset of action of six to 12 weeks.
- Dose is initially 500mg OD, increasing at 500mg weekly intervals to 2–3 g daily in divided doses, enteric coated tablets to be administered.
Haematological abnormalities have occurred with sulfasalazine and, although these are rare, patients should be advised to report unexplained bleeding, bruising, sore throat, fever or malaise.
Patients should also be warned that sulfasalazine can colour urine red and stain contact lenses.
Baseline FBCs and LFTs should be performed and repeated monthly for first 3 months
Leflunomide
Leflunomide inhibits the synthesis of pyrimidine
nucleotides in response cells (particularly T-cells) and reduces proinflammatory cytokines. Studies have shown it to be at least as effective as sulfasalazine and methotrexate, and for quality-of-life measures
some evidence suggests superiority.
Initially 100 mg once daily for 3 days, then reduced to 10–20 mg once daily.
Leflunomide use has been associated with both haematological and hepatotoxic side effects.
FBC and LFTs must be performed before therapy, and every 2 weeks for 6 months, and then every 8 weeks.
When leflunomide and methotrexate are used in combination extra caution is advised.
Leflunomide can also cause hypertension — blood pressure should be checked before starting leflunomide and regularly after.
Effective contraception essential during treatment and for at least 2 years after treatment in women and at least 3 months after treatment in men (plasma concentration monitoring required; waiting time before conception may be reduced with washout procedure)
gold
Although injectable gold (sodium aurothiomalate) has been shown to be efficacious in the management of RA, its use is limited due to its unfavourable side effect profile.
Due to the risk of anaphylaxis an initial 10mg test dose should be given in the first week of treatment, followed
by a maintenance dose of 50mg the following week.
Administration is by deep IM injection. Patients should be monitored for 30 minutes following each dose. FBC and urine (for proteinuria) should be checked after six days, just before giving the next full dose of 50mg IM.
The maintenance dose of 50mg every week is given until the first signs of remission occur. At this point the interval between injections should be extended to two weeks until full remission occurs. The interval between injections
can then be increased progressively to three weeks, four weeks and then, after 18 months to two years, to six weeks.
Azathioprine
Azathioprine is an oral purine analogue that inhibits
lymphocyte proliferation. It becomes biologically active after metabolism by the liver to 6-mercaptopurine. Bone marrow suppression and liver toxicity are associated with its use and FBCs and LFTs should be performed during treatment. Renal function should also be monitored because the drug is renally excreted.
Consider measuring TPMT activity before starting azathioprine.
Initially up to 2.5 mg/kg daily in divided doses, adjusted according to response, rarely more than 3 mg/kg daily; maintenance 1–3 mg/kg daily, consider withdrawal if no improvement within 3 months.
Monitor full blood count weekly for first 4 weeks and then every 3 months.
Azathioprine may also be used for steroid-sparing.
Ciclosporin
Ciclosporin works by impairing the function of B- and Tlymphocytes. Dose-related hypertension and nephrotoxicity are common side effects. FBCs should be performed during treatment and liver and renal function monitored. Ciclosporin drug levels are not routinely measured when it is used for the management of RA.
Initially 1.5 mg/kg twice daily, increased if necessary up to 2.5 mg/kg twice daily after 6 weeks, dose increases should be made gradually, for maintenance treatment, titrate dose individually to the lowest effective dose according to tolerability, treatment may be required for up to 12 weeks.
DaS28 anD itS Significance
DAS28 is a disease activity score based on a 28-joint count. It is calculated from the number of tender and swollen joints, the patient’s ESR or CRP and a self-determined patient assessment of general health status according to a 100mm visual analogue scale.
A score of more than 5.1 indicates high disease activity; ≥3.2 and up to 5.1 indicates moderate disease activity; between 3.2 and 2.6 indicates low disease activity; and <2.6 indicates remission.
DAS28 is often used to determine when treatment with a biologic should be started, and to evaluate the patient’s response. An adequate response is defined as an improvement in the DAS28 of 1.2 points or more. A drawback associated with using DAS28 as an indicator for changing therapy is that some patients may not have particularly high inflammatory markers, but still have severe disease.
DAS28 may also be raised by the perception and reporting of pain by patients and the presence of pre-existing long-term damage. Variations in the score will be caused by different individuals making the assessment, and any sensory, communication or learning difficulties a
patient may have.
When is it appropriate to start a biologic and what is
first-line?
NICE recommends that patients with active RA and a DAS28 of >5.1 who have failed an adequate trial
of at least two DMARDs, including methotrexate (unless
contraindicated), may be started on a biologic medicine.
Biologics - TNF inhibitors: • Sarilumab • Adalimumab • Certolizumab • Etanercept • Golimumab • Infliximab
