Autoimmune diseases stretch far back into the history of humans. Related illnesses even exist in nonhuman primates, such as the baboon model of Chaga's disease. Treatments for human autoimmune diseases have also been around for ages, or at least centuries. In the late 1600s, physicians treated RA with Peruvian bark, which contains quinine. A century later, physicians added willow bark to the arthritis arsenal; it contains salicylic acid, the active ingredient in aspirin. Clinicians also started treating other autoimmune diseases more than a century ago; in the late 1800s, quinine and salicylates were used to treat lupus.

Over the years, other therapies emerged. In 1929, physicians injected gold compounds into patients with RA; these intramuscular injections remained in vogue until the 1990s. Long before that, though, other treatments proved useful. By the middle of the 20th century, scientists discovered the anti-inflammatory capabilities of corticosteroids, which are still used to treat a variety of autoimmune diseases.

Around the same time, the mid-20th century, scientists tried oral-tolerance therapy for diabetes, uveitis, and other autoimmune diseases. With this therapy, patients consume or inhale proteins that resemble those being targeted by autoimmunity. Theoretically, the patient learns to tolerate these proteins. Nonetheless, some scientists feel that oral tolerance has been tried and that it failed.

In recent years, biologics (drugs that mimic natural substances) broadened the selection of drugs that could fight autoimmunity. Tumor necrosis factor (TNF) caught the attention of researchers in the early 1980s: Turning off this cytokine turns down the inflammation associated with RA. A collection of scientific evidence led to using anti-TNF compounds in clinical trials, and by the late 1990s, this work produced three biologics for RA: Enbrel, Humira, and Remicade. More biologics soon followed: Amevive for psoriasis, Avonex and Betaseron for multiple sclerosis, Remicade for Crohn disease, and others.

Anti-TNF therapy fails for many patients, however; only about 25% of RA patients who take anti-TNFs get a 70% or better improvement in their symptoms. Recently, scientists have focused on B cells to fight autoimmunity. This strategy has opened an approval opportunity for drugs with other mechanisms of actions, such as those that destroy autoreactive B cells. One such compound, Rituxan, was approved for patients with moderate to severe cases of RA and who had failed to respond with anti-TNFs.

Today's evolving approach to treating autoimmune diseases involves two basic elements. First, advanced therapies attack specific components or pathways in the immune system. Second, developing various therapies with different mechanisms of action for the same disease allows for the possibility of subsegmenting patient populations - finding patient groups, for example, with some genotypic feature - that benefit more from one form of therapy than another. Clearly, the field has moved a long way from treating patients with ground-up tree bark.