Immune-mediated Inflammatory Diseases: Past and Current Treatments

Christopher T. Ritchlin, MD, MPH, provided the keynote kickoff for the Interdisciplinary Autoimmune Summit virtual meeting April 26 by addressing advances in the treatment of immune-mediated inflammatory diseases (IMIDs) and how the advent of many new biologics has changed the course of care for these conditions during his session, “Immune-mediated Inflammatory Disease Therapeutics: Past, Present, and Future.” Dr Ritchlin is a professor and chief of the department of medicine allergy/immunology and rheumatology at the University of Rochester in Rochester, NY.

In defining IMIDs, he quoted a study that stated they are “a group of diseases where the immune response is inappropriate or excessive and is caused or accompanied by significant dysregulation of the body’s normal cytokine milieu." He continued by introducing 4 key diseases:

• Psoriasis
• Psoriatic arthritis (PsA)
• Axial spondyloarthritis
• Inflammatory bowel disease (IBD)

Past milestones that have impacted the treatment of IMIDs include broad-spectrum immune modulators, intramuscular penicillamine, hydroxychloroquine, sulfasalazine, and, most notably, methotrexate. Dr Rictchlin noted that there was a major change in the approach to rheumatoid arthritis (RA) with the advent of methotrexate, which was followed by COX-2 inhibitors that also had a significant impact on the treatment landscape.

He reminded attendees that after etanercept’s release for RA, physicians treating other IMIDs were so excited about having an alternative that the pharmaceutical company producing etanercept quickly ran out of the drug. What followed was a situation where patients with RA, especially those who had been doing well on etanercept, could no longer obtain the medication. “This was a very trying time for rheumatology for trying to get those patients infliximab and not knowing when the etanercept would be produced in reasonable quantities worldwide,” Dr Ritchlin recalled.

Next, Dr Ritchlin reviewed some of the big changes for IMIDs with the introduction of IL-23 and IL-17 pathways. These were seen to be pivotal in the pathogenesis and progression of IMIDs. “Now we have this family of IL-12, IL-17, and IL-23 cytokines who share common chains and interact in very profound ways in terms of differentiation of cells producing IL-17 by IL-23,” he stated. However, he added that there are IL-23-independent mechanisms.

He continued by showing the range of agents that have been developed over a short period of time to block these cytokines and decrease pain and inflammation in patients with IMIDs. He also added that the Janus kinase inhibitors (JAKs) tofacitinib and upadacitinib have been significantly effective for treatment of patients with IMIDs.

He then transitioned into the current US Food and Drug Administration (FDA)-approved agents for IBD, which include:

• Infliximab
• Adalimumab
• Vedolizumab
• Ustekinumab
• Tofacitinib
• Ozanimod
• Upadacitinib and more

These drugs, with the most recent approvals for IL-23 inhibitors, present a remarkable growth of biologic treatments for IBD, Dr Ritchlin noted.

For PsA, there are significantly extensive treatment options. About 16 or 17 drugs have been approved by the FDA, which Dr Ritchlin called “fantastic” because the only options previously available were disease-modifying antirheumatic drugs (DMARDs) that had been used for RA when it was believed that RA and PsA had similar disease mechanisms. Currently, conventional DMARDS, anti-TNFs, anti-IL-17s, anti-IL-23s, JAK-STAT agents, and various adjunct therapies make up the treatment options for PsA.

Finally, Dr Ritchlin posed the question, “What are the strategies underway to improve PsA outcomes now?” To start, he stated, there is a need to uncover a new cell pathway. This consists of a cell subset, an anti-inflammatory approach, the application of stratification markers, and earlier intervention of present onset of arthritis by treating psoriasis.

“These [strategies] include improved recognition and early treatment of chronic pain, which is a major goal right now of the [National Institute of Arthritis and Musculoskeletal and Skin Diseases]; team care; and, lastly, lifestyle modification,” he concluded.

Reference
Ritchlin CT. Immune-mediated inflammatory disease therapeutics: past, present, and future. Presented at: Interdisciplinary Autoimmune Summit; April 26–28, 2023; Virtual.