Biologics – What Makes Them Different from Immunosuppressives?

In 2025, The American College of Rheumatology (ACR) updated their guidelines for the treatment of Systemic Lupus Erythematosus (SLE) with the goal of clinical remission or low disease activity to prevent accumulating damage. These updated guidelines include universal use of hydroxychloroquine (PLAQUENIL®), tapering glucocorticoid use, and introduction of immunosuppressives for organ-threatening lupus. In addition, the new guidelines recommend earlier introduction of biologic therapies to reduce long-term glucocorticoid use, especially in those who have not responded to conventional therapies. Immunosuppressive medications broadly suppress the entire immune system to stop it from attacking healthy organs. The most common immunosuppressive medications prescribed for the treatment of lupus include azathioprine (Imuran®), mycophenolate mofetil (CellCept®), cyclosporine, methotrexate, cyclophosphamide (Cytoxan®), and leflunomide (Arava®). Conversely, biologic medications such as belimumab (BENLYSTA®) and anifrolumab (SAPHNELO®), are used to treat SLE by targeting very specific pathways such as B-cells or interferon receptors to reduce inflammation with more precision than broad immunosuppressives. Rituximab (RITUXAN®), which targets CD20+B cells, is also used “off label” to treat severe lupus. It is typically used when other treatments fail.

Overview of Differences Between Immunosuppressives and Biologics:

1) Target & Mechanism of Action: Immunosuppressives reduce overall immune activity by broadly inhibiting the immune system. They lead to a higher risk of infection because they target the entire immune system. Whereas biologic therapies are laser focused on certain immune pathways aimed at reducing organ damage and flares.

2) Administration: Immunosuppressives generally come in pill form or via injection.
Biologics are generally administered via infusion or auto injector.

3) Treatment: Immunosuppressives are generally used for moderate to severe organ-threatening lupus and biologics are used for moderate to severe systemic lupus when other standard treatments have failed or are not fully effective.

4) Origin: Immunosuppressives are generally derived from synthetic chemical compounds. Biologics are derived from living organisms such as human or murine (mouse) cells and are complex and large.

5) Steroid Sparing: Both immunosuppressives and biologics allow for a reduction on corticosteroids which decreases long-term side effects.

6) Combination Therapy: immunosuppressive medications can be used alongside
biologic therapies for treatment of lupus, especially for those with Lupus Nephritis (LN). Biologic therapies for LN include belimumab (BENLYSTA®),
anifrolumab (SAPHNELO®), and obinituzimab (GAZYVA®)

Both immunosuppressives and biologic therapies are essential to managing lupus, especially for those with moderate to severe disease activity. All patients should have an open dialogue about the use of either immunosuppressives and/or biologic therapies to control their disease with their physician. It is essential that lupus patients share in the decision-making process about the use of medications to treat their lupus.

This article was medically reviewed by Stanley Ballou, MD on April 17, 2025.