Drugs Used in Rheumatoid Arthritis

Question 1

Drugs for Rheumatoid Arthritis

Answer 1

DRUGS FOR RHEUMATOID ARTHRITIS

Three classes of drugs are used in the treatment of rheumatoid arthritis: NSAIDs, glucocorticoids, and DMARDs (Disease Modifying AntiRheumatic Drugs).

NSAIDs and glucocorticoids have a short onset of action while DMARDs can take several weeks or months to demonstrate a clinical effect.

NSAIDs offer mainly symptomatic relief; they reduce inflammation and the pain it causes and often preserve function.

Oral corticosteroids can relieve joint symptoms and control systemic manifestations, but their chronic use can cause many complications.

Neither NSAIDs nor glucocorticoids prevent disease progression or joint destruction.

The DMARDs are a miscellaneous group of drugs with the potential to reduce or prevent joint damage.

DMARDs have no immediate analgesic effects, but over time can control symptoms and have been shown to delay and possibly stop progression of the disease.

The effects of disease-modifying therapies may take 6 weeks to 6 months to become clinically evident, although some biologics are effective within 2 weeks or less.

Methotrexate is generally the first DMARD prescribed; it can be used in mild, moderate or severe rheumatoid arthritis.

Biologic DMARDs, particularly the tumor necrosis factor (TNF) inhibitors, are generally reserved for use in moderate to severe disease.

Question 2

Methotrexate

Answer 2

NON-BIOLOGIC DMARDS

METHOTREXATE

DMARD of first choice to treat rheumatoid arthritis. Doses of methotrexate required for rheumatoid arthritis are much lower than those needed in cancer chemotherapy and are given once a week; therefore adverse effects are minimized.

Question 3

Leflunomide

Answer 3

NON-BIOLOGIC DMARDS

LEFLUNOMIDE

Leflunomide seems to be as effective as methotrexate at reducing disease activity and progression.

Patients who do not respond to methotrexate alone may benefit from combination therapy with leflunomide and methotrexate.

Question 4

Hydroxychloroquine

Answer 4

NON-BIOLOGIC DMARDS

HYDROXYCHLOROQUINE

Hydroxychloroquine is moderately effective for mild rheumatoid arthritis and is usually well tolerated. It has the least toxicity of any of the DMARDs but also is the least effective as monotherapy.

It is often used with other drugs, particularly methotrexate and sulfasalazine. The drug’s effectiveness may require 3-6 months to become apparent.

Question 5

Sulfasalazine

Answer 5

NON-BIOLOGIC DMARDS

SULFASALAZINE

Sulfasalazine is effective in rheumatoid arthritis.
Beneficial effects typically require 2-3 months to become apparent.

Question 6

Cyclosporine

Answer 6

NON-BIOLOGIC DMARDS

CYCLOSPORINE

Cyclosporine can be helpful in some patients with rheumatoid arthritis, but nephrotoxicity and many interactions with drugs and foods have limited its use.

Question 7

Azathioprine

Answer 7

NON-BIOLOGIC DMARDS

AZATHIOPRINE

Azathioprine is sometimes used for patients with refractory rheumatoid arthritis or systemic involvement such as rheumatoid vasculitis.

Question 8

Cyclophosphamide

Answer 8

NON-BIOLOGIC DMARDS

CYCLOPHOSPHAMIDE

Cyclophosphamide is generally limited to the most severe cases of rheumatoid arthritis with systemic features such as vasculitis. Long-term use increases risk of infection and malignancy.

The drug appears to be active against rheumatoid arthritis when given orally but not when given IV.

Question 9

Adalimumab

Answer 9

BIOLOGIC DMARDS

ANTI-TNF-α DRUG

Question 10

Infliximab

Answer 10

BIOLOGIC DMARDS

ANTI-TNF-α DRUG

Question 11

Etanercept

Answer 11

BIOLOGIC DMARDS

ANTI-TNF-α DRUG

Question 12

ANTI-TNF-α DRUGS

Answer 12

BIOLOGIC DMARDS

TNF-α effects are mediated by specific membrane-bound TNF receptors (TNFR1, TNFR2).

Although a wide range of cytokines are expressed in the joints of rheumatoid arthritis patients, TNF-α appears to be particularly important in the inflammatory process.

TNF inhibitors act more quickly than nonbiologic DMARDs.

Use of TNF inhibitors in combination with methotrexate has synergistic beneficial effects.

Question 13

Rituximab

Answer 13

BIOLOGIC DMARDS

RITUXIMAB

Commonly given concurrently with methotrexate or another nonbiologic DMARD.

Question 14

Abatacept

Answer 14

BIOLOGIC DMARDS

ABATACEPT

Effective in some patients who did not respond to nonbiologic DMARDs or anti-TNF agents.

Question 15

Anakinra

Answer 15

BIOLOGIC DMARDS

ANAKINRA

Approved for moderate to severe rheumatoid arthritis. Modestly effective.

Question 16

Glucocorticoids

Answer 16

GLUCOCORTICOIDS

Oral corticosteroids can relieve joint symptoms and control systemic manifestations, but their chronic use can cause many complications.

Many rheumatologists use short courses of low-dose corticosteroids for symptomatic relief until the beneficial effects of DMARDs become apparent.

The effect of glucocorticoids on rheumatoid arthritis is prompt and dramatic.

ADVERSE EFFECTS

The adverse effects of systemic glucocorticoids include osteoporosis, weight gain, fluid retention, cataracts, poor wound healing, gastric ulcers, GI bleeding, hyperglycemia, hypertension, adrenal suppression and increased risk of infection.

Intra-articular injection of a corticosteroid can often relieve an acutely inflamed rheumatoid joint with minimal adverse effects.

Question 17

NSAIDS

Answer 17

NSAIDs

NSAIDs have immediate analgesic and antiinflammatory effects. NSAIDs are used mainly as bridge drugs for relief of symptoms.

Question 18

Choice of Drugs

Answer 18

CHOICE OF DRUGS

For initial treatment of rheumatoid arthritis, most clinicians prescribe a non-biological DMARD and add a NSAID or a corticosteroid to control symptoms.

Methotrexate is generally the DMARD of choice.

Hydroxychloroquine and sulfasalazine may be appropriate in the mildest cases.

In patients with moderate to severe disease, combining a biologic DMARD with a non-biologic DMARD (usually methotrexate) for initial treatment may provide better disease control than a DMARD alone.

TNF inhibitors are typically the first-line biologic agents prescribed.

For patients who do not respond adequately to one TNF inhibitor, switching to another TNF inhibitor or a non-TNF biologic agent may be effective.

Question 19

Combination Therapy

Answer 19

COMBINATION THERAPY

Combination DMARD therapy may be more effective than monotherapy without a significant increase in toxicity.

Combination therapy typically includes weekly methotrexate, to which other agents are added.

Hydroxychloroquine has little toxicity and is often used with other drugs, particularly methotrexate and sulfasalazine.

Leflunomide in combination with methotrexate increases risk of hepatotoxicity: patients must be monitored closely.

The combination of different biological agents increases the risk of infection and is not recommended.