Therapeutic Management of Rheumatoid Arthritis

1) Pathophysiology and clinical manifestations

Rheumatoid arthritis (RA) is a chronic autoimmune condition. The exact cause of RA is unknown but it is influenced by genetic, hormonal and environmental factors. RA is characterised by inflammation of the synovium joints, typically affecting the proximal interphalangeal joints (PIPs) and metacarpophalangeal joints (MCPs) of the hands, knees, wrists and joints of the feet. Extra-articular manifestations may also affect other organs of the body. There is no cure for RA (Whittlesea and Hodson, 2018). Diagnosis requires a blood test, measuring serum rheumatoid factor and anti-CCP antibodies. To determine erosions, X-ray of the hands and feet should be taken. If RA is active, healthcare professionals should measure disease activity for e.g. DAS 28 and C-reactive protein. The tool that can be used to measure the functional ability is the Health Assessment Questionnaire. The aim of treatment is to reach remission or low disease activity. This should be monitored monthly in specialist care until this target is reached (NICE, 2018).

2) Therapeutic management

In England the treatment of rheumatoid arthritis should be according to the National Institute of Health and Care Excellence (NICE) Rheumatoid arthritis in adults: management.  The aim is to improve the quality of life by slowing the progression of the disease and controlling the symptoms (NICE, 2018).







Pain relief


e.g. ibuprofen + lansoprazole

Control symptoms

Ibuprofen: 300-400mg TDS/QDS; (max: 600mg QDS)

Lansoprazole: 15-30mg OD

Ibuprofen: Renal function, monitor for side effects e.g. GI bleeds/function

Lansoprazole: serum magnesium levels

Ibuprofen: Renal function is monitored if there is renal impairment

Lansoprazole: before treatment


0.5-1g every 4-6 hours (max: 4g/day)

Monitor side effects e.g. nausea and vomiting for as a result of toxicity/overdose

This is rare but can occur with 24 hours of consuming paracetamol

Compound analgesics

e.g. co-codamol 8/500

8/500-16-1000mg every 4-6 hours (max 64/4000mg/day)

Renal function, liver function tests (LFT) if impaired

Monitor at regular intervals if impaired/reduce dose

Bridging therapy


e.g. prednisolone (PO, IM or IA)

Manage symptoms

Prednisolone (PO): 7.5mg OD

Monitor for side effects e.g. GI effects

When signs/symptoms appear, stop treatment and contact healthcare professional



line treatment



Control disease progression

7.5mg once weekly (maximum:20mg/week)

  • Renal function
  • LFT
  • Full blood count (FBC)

Every 1-2 weeks until treatment is stabilised, thereafter every 2-3 months.


500mg OD increased by 500mg/week, maximum 2-3g in divided doses

Every month for the first 3 months.


initially 100mg OD for 3 days, then reduced to 20mg OD

  • FBC
  • LFT
  • Blood pressure (BP)
  • FBC: Before treatment, every 2 weeks for 6 months then every 8 weeks
  • LFT: Every 2 weeks for the first 6 months, then every 8 weeks
  • BP: Every check-up appointment

Alternative 1


line treatment


200-400mg OD, maximum 6.5mg/kg/day

  • Renal and LFT
  • Ophthalmological examination
  • FBC
  • Renal and LFT: before treatment
  • Eye tests yearly
  • Monthly

Step-up treatment:

Escalate dose, if target treatment not reached then offer another cDMARD (combination cDMARD).

Step-down treatment:

If treatment target has been maintained with 2 or more DMARDS for at least 1 year without glucocorticoids, consider reducing doses/stopping drugs. If unsuccessful return to previous treatment.

Further treatment if inadequate response to cDMARDs (severe disease)

Biological DMARDs in combination with methotrexate, monotherapy only if methotrexate is not tolerated

e.g. rituximab, sarilumab, tocilizumab

Control disease progression

Tocilizumab (IV/SC): IV- 8mg/kg every 4 weeks (max. 800mg)

SC- 162mg once weekly, to abdomen, thigh or upper arm.

  • Hepatic transaminases
  • Lipid profile
  • Neutrophil and platelet count (FBC)
  • Monitor for demyelinating disorders during treatment
  • Every 4-8 weeks for the first 6 months, then every 12 weeks
  • 4-8 weeks after starting treatment
  • 4-8 weeks after starting treatment
  • Signs include numbness, blurred vision, check

Non-Pharmacological treatment



Occupational therapy


Hand exercise programmes




Psychological interventions


Diet and complementary therapies


To help adults adjust to their living with RA.

Table 1: Therapeutic management of rheumatoid arthritis (Adapted from NICE, 2018)



has been chosen because it allows disease control and is recommended first-line in patients with rheumatoid arthritis according to NICE (2018).  Strand et al. (1999), found that methotrexate was more efficacious in improving signs and symptoms and delaying disease progression in patients with active RA in comparison to the placebo group (35% vs 19%, ARR=16, NNT=7, P<0.001). The efficacy of treatment was determined by achieving an American College of Rheumatology (ACR) ≥20% after 12 months. A limitation of this study was that patients were commonly taking NSAIDs which would have influenced the improvement in symptoms.

Tocilizumab (biologic)

has been chosen because it is recommended by NICE as a further treatment option in the management of RA. Jones et al. (2009),  found that patients taking tocilizumab 8mg/kg every 4 weeks for moderate- severe RA had a better treatment response rate,  compared to methotrexate 7.5mg-20mg/week with an NNT of only 6 people (69.9% vs 52.5%, ARR=17.4%, P<0.001). The primary endpoint was determined by the number of patients achieving ACR 20 at week 24. A Limitation of this study is that treatment was only carried out for 24 weeks, hence the result may have differed (I.e. not maintained in remission/low disease activity) if carried out for longer or if a follow up was introduced.

Prednisolone (glucocorticoid)

has been chosen because it is recommended by NICE as a bridging therapy to help control the symptoms in patients with RA. Sevnsson et al. (2005) found more patients reached disease remission after 2 years of taking prednisolone, in comparison to no prednisolone (55.5% vs 32.8%, ARR=22.7, NNT=5, P<0.0005). The primary endpoint of disease remission was defined as DAS 28<2.6. A limitation of this study was that in addition to prednisolone the choice of DMARDs was left to the physicians. This may have affected the results as the prednisolone group may have had different DMARD than the no prednisolone group. Therefore the DMARD may have been responsible for the increased number of patients in remission rather than the prednisolone.

3) Pharmacist’s contribution to patient care


side effect

of methotrexate is gastrointestinal (GI) discomfort (BNF, 2018).Jones et al. (2009) found it to be the second most common adverse effect. Methotrexate inhibits the enzyme dihydrofolate reductase affecting the synthesis of cells in the GI tract. The occurrence is reduced by supplementation of folic acid. Pharmacists should inform patients to consume folic acid 24-48 hours post methotrexate dose, and consume methotrexate after meals.

Methotrexate is


in liver toxicity because it can be exacerbated leading to liver cirrhosis which is fatal (BNF, 2018). Pharmacists should identify patients with abnormal liver function tests (LFT)/biopsy and discontinue treatment. Once abnormalities have returned to normal, balance the need for methotrexate (disease control) against the risk of harm (liver toxicity). Where treatment is deemed essential patients should be monitored more frequently (i.e.LFT).

An important


with methotrexate is the increase risk of toxicity when given with aspirin (BNF, 2018). This is because the clearance of methotrexate is reduced. Pharmacists should warn patients and report immediately any signs of blood disorders (i.e. sore throat, bruising and mouth ulcers), liver toxicity (i.e. dark urine, nausea and vomiting) and respiratory effects (i.e. shortness of breath).

Pharmacists should educate patients to avoid self-medication with ibuprofen to reduce risk of toxicity (BNF, 2018).

A common

side effect

of tocilizumab is dyslipidaemia (BNF, 2018). Soubrier et al. (2016), found tocilizumab to increase lipid levels. The exact cause is unclear but it is thought to be due to the inhibition of IL-6. Pharmacists should identify these patients and advise on additional treatments (i.e. atorvastatin).



with tocilizumab is low platelet count (BNF, 2018). Pharmacists should emphasise and encourage patients to go for their regular blood tests to ensure they are monitored.

An important


with tocilizumab is that there is an increased risk of infection if given with influenza vaccine (live) (BNF, 2018). This is because tocilizumab supresses the immune response. Pharmacists should counsel patients not to take the vaccination unless it is essential.

Pharmacists should advise patients to store tocilizumab in the refrigerator (2-8°) ensuring it is stable to maximise the efficacy (BNF, 2018).

A common

side effect

of prednisolone is adrenal suppression (BNF, 2018). Leonie et al. (2015) found that prednisolone inhibits the function of the hypothalamic-pituitary-adrenal axis by negative feedback causing adrenal suppression. Pharmacists should advise patients not to stop treatment abruptly. Prior to treatment cessation, patients should discuss their tapering regimen with a healthcare professional.

Prednisolone is


in diabetes mellitus as it causes hyperglycaemia (BNF, 2018).  Pharmacists should identify patients with diabetes; balance the need for prednisolone (symptom control) against the risk of harm (hyperglycaemia). Where prednisolone is deemed essential, patients should be monitored for any changes in blood glucose levels.

There is a severe


between prednisolone and amiodarone. When given concomitantly it causes hypokalaemia which can lead to torsade de pointes which is fatal. Pharmacists should be vigilant in checking for this interaction, suggesting alternatives (e.g. ibuprofen) to the prescriber.

Pharmacists should advise patients on long-term corticosteroids to carry a steroid treatment card (BNF, 2018). This is to minimise any risks associated with treatment i.e. before surgery.

4) Conclusion

Rheumatoid arthritis is a chronic autoimmune condition negatively impacting the patients’ quality of life. Pharmacological management must be individual taking into account their symptoms and response to medication. The use of cDMARDs and/or biological DMARDS must be tailored to suit the patient to reach target remission/low disease activity.  Pharmacists play a key role in monitoring side effects and counselling patients to optimise their treatment.


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Therapeutic management of rheumatoid arthritis

Drug Name




Drug Group


Biological DMARD


Legal Classification




How the drug works in the condition

Methotrexate inhibits the enzyme dihydrofolate reductase, essential for the synthesis of purines and pyrimidines.

Tocilizumab binds soluble and membrane bound interleukin-6 receptors, preventing IL-6 binding, therefore inhibiting its pro-inflammatory effects

Prednisolone binds to the glucocorticoid receptor. The complex then translocates into the cell nucleus and suppresses IL-2 production reducing pain and inflammation.

The usual adult dose (route, dose, frequency)

Adult: initially 7.5mg once weekly, then increased in steps of 2.5mg once weekly, adjusted according to response; maximum 25mg per week.

Adult,IV infusion


8mg/kg every 4 weeks (maximum per dose 800mg), for dose adjustments in patients with liver enzyme abnormalities, or low absolute neutrophil or platelet count.

Adult, SC: 162 mg once weekly, administer to abdomen, thigh or upper arm, for dose adjustments in patients with liver enzyme abnormalities, or low absolute neutrophil or platelet count.

Adult: 5-25mg, dose according to size; not more than 3 joints should be treated on any one day; where appropriate may be repeated when relapse occurs.

Patient monitoring to check that the drug is working

Disease control. Symptom improvement i.e. flares decreased can be measured against DAS-28 and HAQ.

Lipids: after starting treatment monitor every 4-8 weeks.

Monitor for demyelinating disorders

Liver function tests, transaminases: monitor every 4-8 weeks for the first 6 months, then every 12 weeks.

Symptoms are minimal, i.e. reduced morning stiffness, inflammation and pain reduced and disease is controlled.

Pain and inflammation is reduced.

Important side-effects caused by the drug and monitoring for these side-effects

Side effects: GI side effects including abdominal distress, nausea Headache, leucopoenia, oral disorders,

FBC and renal function and LFTs repeated every 1-2 weeks until therapy stabilised, thereafter patients should be monitored every 2-3months.

Side effects: abdominal pain, dizziness, dyslipidaemia, dyspnoea, gastrointestinal disorders, cough, hypersensitivity, neutropenia

Side effects: abdominal pain, bruising, diarrhoea, dizziness, exophthalmos, hiccups, kaposi’s sarcoma, malaise, vomiting, mayocardial rupture (following recent myocardial infarction).

Important drug interactions

NSAIDs, High dose aspirin

– increase risk of toxicity when given with methotrexate monitor and adjust dose

Live vaccines

– increase the risk of generalised infections


– increase the risk of side-effects when given with methotrexate

BCG, influenza, MMR, yellow fever, rotavirus, varicella zoster vaccine, typhoid oral vaccine= all these vaccines increase the risk of infection


– predicted to cause hypokalaemia when given with prednisolone


– increase risk of digoxin toxicity


– increases the risk of GI bleeding


– decreases exposure to prednisolone

Important disease interactions (Contra-indications and Cautions)


: pulmonary toxicity, bone marrow suppression, GI toxicity, photosensitivity


Active infection, ascites, immunodeficiency syndromes, significant pleural effusion

Contra-indicated: Do not initiate if absolute neutrophil count less than 2 x 10


/litre or if patient has a severe infection.

Caution: Patient with latent tuberculosis should be treated prior to initiating tocilizumab.

Osteoporosis, congestive heart failure

Contra-indicated: systemic infection, live virus vaccines in those receiving immunosuppressive doses

What the patient should be told about their medicine

Report immediately the onset of any feature of blood disorders (e.g. sore throat, bruising and mouth ulcers), liver toxicity (e.g. nausea, vomiting, abdominal discomfort, and dark urine), and respiratory effects (e.g. shortness of breath).

Take folic acid alongside methotrexate

Patients should be advised that this medicine may affect driving or performance of skilled tasks e.g. dizziness.

Patients should seek immediate medical attention if symptoms of: infection, diverticular perforation such as abdominal pain occur. As well as haemorrhage, or fever accompanying change in bowel habits.

Pregnancy: it crosses the placenta, 88% of prednisolone is inactivated

Breast-feeding: appears in small amounts in breast milk but maternal doses of up to 40mg daily are unlikely to cause systemic effects in the infant.

Patients on long-term corticosteroid treatment should carry a steroid treatment card.

Mood and behaviour changes (i.e. more irritable, confused) with high doses.