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An elegant article in from psoriatic arthritis erudites, Drs. Scher, Ogdie, Merola, and Ritchlin, is bringing to everyone's attention the discussion about combination therapy in the complex field of seronegative spondyloarthropathies -- specifically psoriatic arthritis (PsA). As I often tell medical students and trainees, PsA involves a number of anatomical structures, and one could not evaluate its status without counting at least five domains: skin, nails, digits, joints, and entheses. While each domain might be contributing differently to the overall disease activity, they are equally important and likely driven by different mechanisms.

The authors pose a philosophical question: considering the methotrexate combination data in rheumatoid arthritis, why adding a small molecule/traditional DMARD to a biological DMARD made no difference in PsA? Do we have to cross the scary line of combining two biologics? And if yes, which ones?

The authors discuss synergism of the TNFi and IL-23/IL-17 axis, along with benefits of sequential "heavy upfront" combination therapy followed by "maintenance" with monotherapy and adapting the combination therapies (TNFi plus PDE-4i) in arthritis-dominated phenotypes versus IL-23 or IL-17 in skin-dominating phenotypes. They reference the phase 2 VEGA study evaluating guselkumab in combination with golimumab versus each monotherapy in ulcerative colitis -- as a very important data cornerstone in seronegative spondyloarthropathies.

Either way, the authors take a glimpse at the future that includes advanced imaging such as PET-CT, and incorporation of novel imaging modalities (i.e., evaluation of subclinical changes on whole body MRI or musculoskeletal ultrasound) that have the potential to document the achievement of "deep tissue remission." Having the ability to assess, at any given time or treatment sequence, the level of tissue inflammation, is almost as important as figuring out the right combination of drugs.

The article is thought provoking and answers a lot of the questions treating rheumatologists face every day.

Elena Schiopu, MD, is associate professor at Michigan Medicine in Ann Arbor.

Read the study here and an interview with the first study author here.