Predicting and monitoring disease course in rheumatoid arthritis : imaging, biomarkers, risk factors, and integrative medicine

Rheumatoid arthritis (RA), the most common inflammatory arthritis, is a chronic, potentially debilitating autoimmune disease that can lead to functional disability, bone erosion, and chronic pain. The modern era of treatment has led to major advancements in treating this condition, especially if patients are treated early within a ‘window of opportunity’ with potent disease-modifying antirheumatic drugs (DMARDs) and a ‘treat-to-target’ approach aiming towards low disease activity or remission. Personalized integrative medicine may lead to further advancements in the care of individuals suffering from autoimmune conditions such as RA through the application of imaging, biomarker and risk factor identification, and integrative manual therapy.

After simulating a true radiographic progression control group in several randomized clinical trials, early application of intensive or biological DMARDs was demonstrated to be superior to conventional monotherapy in early RA, and that rheumatoid factor-positive patients on an intensive strategy may benefit more with a half-year induction of anti-tumor necrosis factor (TNF) therapy (Papers I-II).

For the first time, it was revealed that the proto-oncogene survivin, expressed in one third of patients with early RA, prevents a sustained clinical response to gold-standard methotrexate. Additionally, further allocation to combination DMARDs may be favorable to the allocation of anti-TNF therapy among survivin-positive patients (Paper III).

Lifestyle risk factors were shown to play an important role in early RA disease outcome, and obesity in particular was found to be a strong independent predictor of long-term non-remission, in addition to smoking. Obesity was associated with worse clinical outcomes over time, measured by disease activity, pain, and functional disability (Paper IV).

A novel approach was explored with integrative manual mobilization therapy and its potential to further enhance patient care in RA. This was demonstrated through systemic subjective and objective hand improvements – including pain, synovial fluid, and joint space (Paper V).

Together with the goal of aiming for early, tight RA disease control, when utilizing imaging tools; identifying biomarkers and lifestyle risk factors; and applying integrative medicine, allopathic practice can move towards even better proactive patient care in RA. Altogether, these findings support the value of incorporating personalized integrative medicine into clinical practice for patients with RA.

List of scientific papers

I. Adrian Levitsky, Kristina Forslind, Ronald F. van Vollenhoven; SWEFOT trial group. Predicted vs. observed radiographic progression in early rheumatoid arthritis (POPeRA): results from a randomized trial. Scandinavian Journal of Rheumatology. 2015;44(5):348-53.
https://doi.org/10.3109/03009742.2015.1019560

II. Adrian Levitsky, Marius Wick, Timo Möttönen, Marjatta Leirisalo-Repo, Leena Laasonen, Markku Korpela, Ronald F. van Vollenhoven, Vappu Rantalaiho. Early treatment intensification induces favourable radiographic outcomes according to predicted versus observed radiographic progression in early rheumatoid arthritis: a subanalysis of the randomized FIN-RACo and NEO-RACo trials. Clinical and Experimental Rheumatology. 2016 Nov-Dec;34(6):1065-1071.
https://pubmed.ncbi.nlm.nih.gov/27607411

III. Adrian Levitsky, Malin C. Erlandsson, Ronald F. van Vollenhoven, Maria I. Bokarewa. Serum survivin predicts responses to treatment in active rheumatoid arthritis: a post hoc analysis from the SWEFOT trial. BMC Medicine. 2015 Sep 30;13:247.
https://doi.org/10.1186/s12916-015-0485-2

IV. Adrian Levitsky, Kerstin Brismar, Ingiäld Hafström, Karen Hambardzumyan, Cecilia Lourdudoss, Ronald F. van Vollenhoven, Saedis Saevarsdottir; SWEFOT trial group. Obesity is a strong predictor of worse clinical outcomes and treatment responses in early rheumatoid arthritis: results from the SWEFOT trial. [Submitted]

V. Adrian Levitsky, Yogan Kisten, Sara Lind, Patric Nordström, Helene Hultholm, Jessica Lyander, Viveka Hammelin, Cidem Gentline, Ioanna Giannakou, Francesca Faustini, Eva Skillgate, Ronald F. van Vollenhoven, Tobias Sundberg. Joint mobilization of the hands in rheumatoid arthritis: Results from an assessor-blinded, randomized crossover study. [Submitted]