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Biologic therapies have been widely embraced by the rheumatologic community for their remarkable efficacy and safety profiles. Unlike older therapies that suppress global immunity, biologics can precisely target individual cytokines, cell types or pathways, leave the rest of the immune system untouched, and may be better at sparing patients the infection and toxicities associated with conventional immunosuppresants.

Today at The Children’s Hospital at Montefiore (CHAM) and Albert Einstein College of Medicine (AECOM), rheumatologists are examining next-wave biologic agents that promise to deliver new therapeutic options to patients with arthritis – including children with severe, refractory disease.

Targeted Therapies Zero In on Multipathway Disease
The novel therapies that are available and that are currently in development are particularly efficacious for rheumatologic disorders because many rheumatic inflammatory disorders can involve “not just one abnormality in a single cytokine,” explains Chaim Putterman, MD, chief, Division of Rheumatology, Montefiore Medical Center, “but abnormalities in multiple pathways. In lupus, for example, there are abnormalities in B cells, T cells, cytokines and cell-signaling molecules – multiple potential abnormalities, each of which may need to be addressed therapeutically. Therefore, targeting the treatment to the specific defect present in a given patient may be the most effective approach, with the least side effects.”

“Anti-TNF Revolution” Spurs Innovation in Emerging Biologic Therapies
The first generation of rheumatologic biologics were TNF-blockers – agents that deactivate tumor necrosis factor (TNF), a chemical messenger in arthritic inflammation. The drugs were “a prototypical benchto- bedside success story,” notes Dr. Putterman, and this “anti-TNF revolution” continues to drive ongoing biologic investigations, he says.

CHAM Researcher Forges New Ground With Next-Wave Biologics
Forward-looking researchers are now examining biologics that inhibit interleukin-1 (IL-1), an “accessory protein needed to trigger inflammatory cells,” says Norman Ilowite, MD, chief, Pediatric Rheumatology, CHAM. As principal investigator (PI) of a National Institutes of Health (NIH)-funded study of the IL-1-inhibitor anakinra, Dr. Ilowite reported a 79 percent response rate from patients with systemic juvenile rheumatoid arthritis (JRA) – the most severe and therapy-resistant JRA subset.

Concurrently the PI in a study of another IL-1 inhibitor, IL-1-trap, Dr. Ilowite also hopes to “identify children who will respond to therapy before we give the medicines,” he says. The IL-1-trap trial is the first ever non-industry-sponsored investigation of a JRA therapeutic.

Futuristic B Cell Inhibitors Slam the Door on Inflammatory Cell Conversations
In yet another study, Dr. Ilowite and his pediatric rheumatologic team will collaborate with Dr. Putterman and other members of the adult rheumatology team to explore treatment with an anti-CD22 monoclonal antibody. This B cell inhibiting biologic interferes with cellular “costimulation – the conversation,” explains Dr. Putterman, that occurs “between antigen-presenting cells and B cells” as part of rheumatic inflammation.

Researchers Create Rheumatologic Genetic Bank
At CHAM and AECOM, rheumatologic colleagues will also join forces on an “observational, longitudinal study of systemic lupus erythematosus,” says Dr. Putterman, “to see whether certain serum and urine markers will help predict disease course – or if we can use them to prognosticate flares and relapses.”

The study will bank collected biomarkers and genetic data to allow CHAM researchers – and scientists around the country – to “do cross-sectional studies as well as retrospective and prospective studies with multiple patients,” says Dr. Putterman.

Translational Medicine That Really Translates
“There is a very, very close integration,” says Dr. Putterman, “between the clinical and research efforts” at CHAM and AECOM. Dr. Putterman encourages “collaboration between the people providing patient care and the people asking the questions in the lab,” he says, adding, “To improve the lot of patients … we need everybody to be versed in the language of the other.”

Fast Facts on Rheumatologic Therapeutics

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