Problem 4: Treatment Options for Progressing RA Flashcards
Explain the role of sulfasalazine in RA and its monitoring requirements?
Sulfasalazine is a medicine formed from salicylic acid (the active ingredient in aspirin) and an antibiotic, sulfapyridine.
Sulfasalazine is a medicine formed from salicylic acid (the active ingredient in aspirin) and an antibiotic, sulfapyridine.
Pharmacology: Around 90% of a dose reaches the colon where bacteria split the drug into sulfapyridine (SP) and mesalazine (ME). These are active, and the unsplit sulfasalazine (SASP) is also active on a variety of symptoms.
Describe how the response to treatment may be measured?
Measure CRP and key components of disease activity (using a composite score such as DAS28) regularly in people with RA to inform decision-making about:
- increasing treatment to control disease
- cautiously decreasing treatment when disease is controlled.
In people with recent-onset active RA, measure CRP and key components of disease activity (using a composite score such as DAS28) monthly until treatment has controlled the disease to a level previously agreed with the person with RA.
In established RA, offer review with frequency and location that is convenient to patient. Annual review at most controlled.
Identify and appraise the next available therapeutic options for Mrs Li
After DMARDs, biological DMARDs and rituximab are used
APPRAISE BIOLOGICALS
Describe how anti-TNF inhibitors work
Tumour necrosis factor alpha or TNFα is a cytokine. Cytokines are substances released by the body during inflammation. An excessive amount of TNFα is present in the blood and joints of patients with rheumatoid arthritis.
TNFα is a particularly powerful cytokine because it causes the release of other cytokines from the body (such as IL1 and IL6). Blocking TNFα can reduce inflammation and joint damage.
NICE guidelines
The patient must have tried at least 2 of the standard DMARDs (such as methotrexate, sulfasalazine, hydroxychloroquine and leflunomide) and one of these must be methotrexate.
The level of disease (measured using an assessment called ‘disease activity score’ or ‘DAS’) should be above 5.1 on two occasions, one month apart. DAS is calculated by a combination of factors, including assessing 28 joints to see if they are swollen/tender and looking at the levels of inflammation showing up in your blood. (click here for more information on DAS).
Discuss the various factors to consider when prescribing anti-TNFa therapy including supply and administration? What about any adverse effects or contraindications?
Disease state - DAS2 score 5.1
Medication tried already; DMARDs, biologicals beforehand?
therapy has not been optimised or because of intolerance to drugs. Pharmacists can help patients manage their medicines, advise on side effects and, with specialist training, perform prescribing and monitoring roles.
Describe key features of rituximab and identify its role in therapy for RA?
These so-called biologic disease modifying anti-rheumatic medications (DMARDs) differ from the traditional DMARDs, such as methotrexate, in that they target specific molecules which are responsible for the inflammation occurring in the joints and other tissues in RA.
Rituximab, (also known as Mabthera or Rituxan) is an antibody which is directed against B-cells, specifically a marker on certain types of B-cells called CD-20. Rituximab binds specifically to the transmembrane antigen, CD20, a non-glycosylated phosphoprotein, located on pre-B and mature B lymphocytes.
In rheumatoid arthritis patients, immediate depletion of B cells in the peripheral blood was observed following two infusions of 1000 mg MabThera separated by a 14 day interval.
Name DMARDs
Methotrexate, Leflunomide, Sulfalazine, Hydroxychloroquine
What is DAS2?
Measures of response to treatment include the American College of Rheumatology (ACR) response criteria (ACR20, 50 and 70). These require a specified improvement in tender joint count, swollen joint count, global assessments, pain, disability and an acute‑phase reactant (for example, erythrocyte sedimentation rate or C‑reactive protein). The disease activity score (DAS28) is an alternative scoring system that has been developed in Europe. It is calculated using a formula that includes counts for tender and swollen joints, an evaluation of general health by the person (on a scale of 0–100), and erythrocyte sedimentation rate or C‑reactive protein. A DAS28 greater than 5.1 indicates high disease activity, between 3.2 and 5.1 moderate disease activity, and less than 3.2 low disease activity. A score of less than 2.6 indicates disease remission.
Which biological DMARDs are available for treatment of RA?
Rituximab
Infliximab
Etanercept
Adalimumab
How is rituximab administered?
Are there any potential adverse effects?
Rituximab is currently administered as an infusion of 1 gram given twice (two weeks apart) on a background of methotrexate. The infusions last between 3-5 hours and are given in special infusion centres in the hospital setting. A small dose of corticosteroid, anti-histamine and paracetamol are also administered at the time of the injection to reduce the risk of an infusion reaction.
The prepared MabThera solution should be administered as an intravenous infusion through a dedicated line. It should not be administered as an intravenous push or bolus.
Patients should be closely monitored for the onset of cytokine release syndrome (see section 4.4). Patients who develop evidence of severe reactions, especially severe dyspnoea, bronchospasm or hypoxia should have the infusion interrupted immediately.
In RA, an alternative subsequent, faster, infusion schedule can be carried out.
If patients did not experience a serious infusion related reaction with their first or subsequent infusions of a dose of 1000 mg MabThera administered over the standard infusion schedule, a more rapid infusion can be administered for second and subsequent infusions using the same concentration as in previous infusions (4 mg/mL in a 250 mL volume).
