Researchers next turned their attention to creating biologics against the cytokines that are important in RA. One of the first targets was TNF-α, a cytokine with diverse biological activity. The chimeric monoclonal antibody infliximab, initially developed for the treatment of sepsis, was repurposed for RA when rheumatologists began to realize TNF-α dominates the inflammatory process of RA. Infliximab is currently approved for the treatment of many conditions, including RA, Crohn’s disease, ankylosing spondylitis and psoriatic arthritis. It, and other TNFα biologics, dominated rheumatological therapies in the early 1990s.
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Dr. Burmester concluded his talk by stating that biologics are here to stay—despite the fourth milestone of anti-rheumatic therapy, the JAK inhibitors. Rheumatologists now have long-term data about these established reagents and recognize they have an incredibly good safety profile. Moreover, their long half-life means they are long acting. However, they also have disadvantages, including the fact that they can be difficult to manufacture, have complex modes of action and can be difficult to dose. Biologics also have the disadvantage of requiring parenteral administration, and some patients develop an antibody reaction against the therapeutic reagent. Safety signals primarily include infections, such as tuberculosis, which can be minimized by screening for, and the preemptive treatment of, latent tuberculosis.
The science of monoclonal antibodies will likely continue to evolve, explained Dr. Burmester, with investigators creating even more specific antibodies, with fewer off-target effects. In the future, antibodies will also likely be modified to be biospecific and contain, for example, radioactive molecules. Their value will also likely continue to expand beyond rheumatology and extend to meet newly emerging needs, such as SARS-CoV2.
Many rheumatologists will also continue to look to biosimilars as treatments for many rheumatic conditions. An expanding number of biosimilars make the expensive biologics more affordable to a larger population. These biosimilars have a safety profile that is well established by clinical trials and registries.
All told, a great deal has been accomplished in the field of rheumatic treatment, and the use of biologics has continued to increase over time. For example, Dr. Burmester’s review of annual data from the German National Database of the Collaborative Arthritis Centers found biologic treatment strongly increased the number of patients in low disease activity or remission. Unfortunately, however, while treatment modalities have changed substantially over time, many rheumatologists tend to prescribe biologics only to patients with long-standing disease, despite the fact that early intensive treatment adaptation improves disease activity in the many patients who do not achieve low disease activity with treatment with conventional disease-modifying anti-rheumatic drugs.2