18th January 2024

Adverse effects of DMARDs

Conventional DMARDs

Most conventional DMARDs have a similar side effect (SE) profile, including increased risk of infection and GI upset. Certain DMARDs (particularly Methotrexate and Leflunomide) are also teratogenic, so women of childbearing age should ensure they are using adequate contraception. However, there are some adverse effects which are unique to each agent.

Methotrexate, Sulfasalazine and Leflunomide share a similar adverse effect profile, including GI upset, increased incidence of common and serious infections, allergic reactions, bone marrow suppression and hepatotoxicity. Alopecia is a SE of both Methotrexate and Leflunomide. The following unique SEs are also seen:

Methotrexate- pneumonitis and interstitial lung disease, folic acid deficiency, liver cirrhosis, oral ulcers
Leflunomide- hypertension, peripheral neuropathy, weight loss
Sulfasalazine- high risk of GI upset. Can cause decreased sperm count and rarely Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome.

Hydroxychloroquine has perhaps the best safety profile compared to other conventional DMARDs; it does not increase the risk of serious infections or cause renal or liver dysfunction. Common SEs include rash and diarrhoea. The most serious but rare adverse effect associated with Hydroxychloroquine is retinopathy/ maculopathy. This is associated with a higher cumulative dose and greater than 5 years of therapy. Other rare adverse effects of Hydroxychloroquine include anaemia, leukopenia, myopathy and cardiomyopathy.

Biologic DMARDs

All biologic DMARDs can increase the risk of common and serious infections from bacterial, fungal and viral agents. This can also include reactivation of tuberculosis, herpes zoster and hepatitis B and C. Rarer SEs include bone marrow suppression and hepatotoxicity.

Whilst it is acceptable to use a combination of conventional DMARDs or a combination of conventional DMARD and biologic DMARD, a combination of different biologic DMARDs should not be used as the risk of severe immunosuppression reading to severe life-threatening infections is too high.

Specific SEs associated with Anti-TNF agents include: