DMARDs & Biologics

Rheumatoid arthritis and osteoarthritis can both involve the proximal interphalangeal joints of the hands, but metacarpophalangeal joint involvement occurs in rheumatoid arthritis and not osteoarthritis. Distal interphalangeal joint involvement is characteristic of osteoarthritis but not rheumatoid arthritis.

If they are on steroids for more than 3 months and if the dose is more than 5 mg/d, start Ca + Vit D + bisphosphonate suppementation

Oral DMARDs typically take 3 months to produce a clinical response and up to 6 months for a full response. Biologic DMARDs require less time to demonstrate efficacy.

Patients commonly undergo 3 to 6 months of methotrexate therapy; if the clinical response is inadequate, sulfasalazine and hydroxychloroquine, or a tumor necrosis factor α (TNF-α) cyclooxygenase inhibitor, can be added.

Add folic acid to reduce this effects.

The most common severe adverse effect of methotrexate is hepatotoxicity, and a temporary but acute increase in liver enzyme levels may occur. The risk of hepatotoxicity is increased by alcohol consumption, pre-existing liver disease, and possibly diabetes and obesity. Methotrexate also suppresses the immune system and increases the risk for opportunistic infection.

Contraindications to methotrexate therapy include liver disease, abnormal findings on liver chemistry studies, and regular alcohol consumption.

• Measuring serum methotrexate levels is not helpful in monitoring therapeutic efficacy.
• Patients using methotrexate should undergo monthly liver chemistry studies and a complete blood count until the dosage is stable and every 4 to 8 months thereafter.

• Liver biopsy is indicated in patients treated with methotrexate who have persistently elevated liver chemistry study results or decreased serum albumin levels.
• In patients with persistently elevated liver study results, the methotrexate dosage should be decreased or therapy discontinued.

renal or hepatic insufficiency

• Macular toxicity is a severe side effect of hydroxychloroquine therapy but is unlikely at a dosage of 6.5 mg/kg/d or less and rarely occurs before completion of 5 years of treatment. Nevertheless, referral to an ophthalmologist for a baseline examination and routine monitoring every 6 to 12 months is indicated in patients using hydroxychloroquine.
• Nausea and skin discoloration also occasionally occur.

Sulfasalazine is contraindicated in patients with sulfa allergy or glucose-6-phosphate dehydrogenase deficiency

Sulfasalazine

should be monitored for neutropenia and elevated aminotransferase levels every 1 to 3 months

The most common side effects of leflunomide include diarrhea, nausea, and hair loss. Use of a loading dose is associated with diarrhea and hepatotoxicity; this agent is more commonly begun at a dosage of 10 mg/d that, if tolerated, is increased.

• Because leflunomide is teratogenic, women who plan to become pregnant must discontinue this therapy and undergo a course of cholestyramine elimination therapy.
• Women should attempt pregnancy only when serum leflunomide levels are less than 0.02 mg/L on two occasions at least 14 days apart.

Azathioprine is approved for the treatment of rheumatoid arthritis but is more commonly used as a corticosteroid-sparing agent in patients with SLE and systemic vasculitis.

Patients using azathioprine should undergo periodic complete blood counts and liver chemistry studies. Patients with a genetic deficiency of thiopurine methyltransferase (TPMT), the primary enzyme responsible for metabolizing azathioprine, are highly susceptible to serious azathioprine toxicity, such as pancytopenia. Therefore, although this condition is rare, genotype testing for TPMT may be warranted before initiating azathioprine therapy.

Cyclophosphamide is primarily used to treat lupus nephritis and systemic vasculitis and is an effective initial therapy for Wegener granulomatosis.

Frequent complete blood counts and urinalyses, as well as prompt evaluation of gross hematuria, are critical in patients treated with cyclophosphamide. After several months of oral or intravenous therapy, progressive cytopenias may necessitate a dosage reduction.

Mycophenolate mofetil was developed to prevent rejection of transplanted organs but has emerged as an off-label treatment for lupus nephritis, for which it is as effective as intermittent intravenous cyclophosphamide therapy with considerably less toxicity.

Mycophenolate mofetil has been associated with birth defects and is therefore contraindicated during pregnancy. Women of child-bearing age should use effective contraception while taking this agent.

• TNF-alpha inhibitors: etarnecept, infliximab, adalimumab
• Abatacept - for RA
• Rituximab - for RA that is not responsive to TNF-alpha
• Anakinra - for RA and Adult still disease

Stop the biologics

Find out if the patient is on TNF-alpha or biologics because these need to be discontinued.

• Arrange for preconception counselling
• Approx. 75% of women with RA has a remission of their disease that usually begins in the second trimester of pregnancy. During pregnancy, most women with rheumatoid arthritis can therefore safely discontinue therapy for this condition. However, pregnant patients with persistent disease activity may require treatment with low-dose prednisone, which generally is believed to be safe in pregnancy.
• Hydroxychloroquine and sulfasalazine also can be used during pregnancy, if necessary.