Biologic agents and small-molecule inhibitors in systemic autoimmune conditions: an update.Pol Arch Intern Med. 2020 Jun 18 [Online ahead of print]PA
The progress in the understanding of the pathophysiology of rheumatic diseases provided a rational basis for the development of biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) which have completely revolutionized the treatment of inflammatory conditions. These agents differ in their effectiveness for controlling specific rheumatic diseases depending on the pivotal cytokine driving the inflammatory process. Cytokine blockers were the first to be developed and rapidly expanded. They include agents that act against TNFα (etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol), IL-6 receptor (tocilizumab and sarilumab), IL-1 (anakinra, canakinumab, and rilonacept), IL-17 (secukinumab and ixekizumab) and IL12/23 (ustekinumab). Lymphocyte-targeting agents include rituximab and belimumab which act against B cells by different mechanisms and, abatacept which is a T cell co-stimulation modulator. tsDMARDs, also known as small-molecule inhibitors, are oral drugs with a novel strategy to treat inflammatory diseases. JAK inhibitors (tofacitinib, baricitinib, and upadacitinib) and phosphodiesterase 4 inhibitor (apremilast) form this group. The major concern with the use of bDMARDs and tsDMARDs is a higher risk for infections. Performance of blood tests, tuberculosis, and hepatitis viral infection screening is mandatory before the onset of biologic therapy. Adherence to an immunization program is also recommended. Whenever possible, the choice of bDMARDs and tsDMARDs should be influenced by the co-morbidities of each patient. During pregnancy limited data exits, but anti-TNFα, rituximab, and anakinra seem to be safe. Biologic agents are expensive, but biosimilars have raised as a more cost-effective option and an opportunity to treat a greater number of patients.