Indications: Abatacept can be used as monotherapy or in combination with methotrexate or other DMARDs in patients with moderate to severe RA or severe PJIA. It has been tested in combination with methotrexate in early rapidly progressing RA and methotrexate-naïve patients. The combination was superior to methotrexate in achieving minimal disease activity as early as 2 months, significantly inhibiting radiographic progression at 1 year and improving patients’ physical function and symptoms. Such improvement is sustained or improved during the second year. Another trial (ADJUST) tested the effectiveness of abatacept in preventing progression to defined RA in patients with undifferentiated inflammatory arthritis. The results showed that numerically, RA developed in more patients treated with placebo than in those treated with abatacept over 1 year. Abatacept has been tested in other rheumatic diseases like SLE, primary Sjögren’s syndrome, type 1 diabetes, inflammatory bowel disease, and psoriasis vulgaris, but the most beneficial effects were seen in psoriatic arthritis (PsA) patients.
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Adverse Effects: There is a slightly increased risk of infection (as with other biologic DMARDs), predominantly of the upper respiratory or urinary tracts. Concomitant use with TNF-α antagonists or other biologics is not recommended due to the increased incidence of serious infection. All patients should be screened for latent tuberculosis and viral hepatitis before starting this medication. Live vaccines should be avoided in patients while taking abatacept and up to 3 months after discontinuation. Infusion-related reactions and hypersensitivity reactions, including anaphylaxis, have been reported but are rare. Antiabatacept antibody formation is infrequent (<5%) and has no effect on clinical outcomes. There is a possible increase in lymphomas but not other malignancies when using abatacept.
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Mechanism of Action: Azathioprine is a csDMARD that acts through its major metabolite, 6-thioguanine. 6-Thioguanine suppresses inosinic acid synthesis, B-cell and T-cell function, immunoglobulin production, and IL-2 secretion (see Chapter 55).
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Pharmacokinetics: Azathioprine can be given orally or parenterally. Its metabolism is bimodal in humans, with rapid metabolizers clearing the drug four times faster than slow metabolizers. Production of 6-thioguanine is dependent on thiopurine methyltransferase (TPMT), and patients with low or absent TPMT activity (0.3% of the population) are at particularly high risk of myelosuppression by excess concentrations of the parent drug, if dosage is not adjusted.
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Indications: Azathioprine is approved for use in RA at 2 mg/kg per day. It is also used for the prevention of kidney transplant rejection in combination with other immune suppressants.
Controlled trials show efficacy in PA, reactive arthritis, polymyositis, SLE, maintenance of remission in vasculitis, and Behçet’s disease. Azathioprine is also used in scleroderma; however, in one study, it was found to be less effective than cyclophosphamide in controlling the progression of scleroderma lung disease. Another registry study indicated possible usefulness in scleroderma lung disease. Thus it is not clear what place, if any, azathioprine has for treating scleroderma.
4. Adverse Effects: Azathioprine’s toxicity includes bone marrow suppression, GI disturbances, and some increase in infection risk. As noted in Chapter 55, lymphomas may be increased with azathioprine use. Rarely, fever, rash, and hepatotoxicity signal acute allergic reactions.
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