My Take on RA Data From APLAR, JCR, and EULAR 2019

Leonard H. Calabrese, DO

Professor of Medicine
Department of Rheumatology
Cleveland Clinic
Cleveland, Ohio


Leonard H. Calabrese, DO, has disclosed that he has received consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Crescendo, GenPharma, Gilead Sciences, GlaxoSmithKline, Horizon, Janssen, Lilly, Pfizer, Sanofi, and Union Chimique Belge and fees for non-CME/CE services from Bristol-Myers Squibb, GenPharma, Horizon, Janssen, Sanofi, and Union Chimique Belge.


View ClinicalThoughts from this Author

Released: July 23, 2019

At APLAR, JCR, and EULAR 2019, many important abstracts and studies were presented. It is a challenge to succinctly summarize how these meetings with thousands of abstracts and presentations may ultimately change my practice, but I have no doubt that they will.

JAK Inhibitor Therapy
I think it is safe to say we are entering a long-term evaluation phase for kinase inhibitor therapy, where their ascendency may displace many traditional biologics if their efficacy holds up. Studies so far have yielded no surprises, and we expect the costs to be reduced as the earliest patents expire. 

The data on the 2 most advanced investigational drugs—filgotinib and upadacitinib—were comprehensive and impressive across robust trials.

The filgotinib studies FINCH 1 and FINCH 3, presented at EULAR, and FINCH 2, presented at JCR, all demonstrated improved responses with filgotinib vs conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), such as methotrexate.

The upadacitinib studies SELECT-EARLY and SELECT-MONOTHERAPY also demonstrated improved response rates with upadacitinib compared with csDMARDs. Although these and the SELECT pooled safety analysis all demonstrated a numerically higher rate of any adverse event with upadacitinib compared with csDMARDs, no new toxicities were observed for filgotinib or upadacitinib, and there was no evidence of venous thromboembolic disease, which is on everyone’s radar.

In addition to investigational agents, long-term toxicity studies of the approved drugs tofacitinib and baricitinib continue to be reassuring. Data presented at EULAR, APLAR, and JCR suggest that these drugs may continue to move up the ladder of DMARD choices for several reasons:

  • First, in addition to being conveniently oral, they have demonstrated improved responses in head-to-head comparisons with methotrexate. However, despite these data, they are still difficult to access as first-line treatment for patients who are not methotrexate intolerant.
  • Second, they demonstrate rapid clinical efficacy. Although some clinicians say this is meaningless for a chronic disease, in my opinion faster is better for our patients.
  • Lastly, rheumatologists are risk-adverse, so safety data based on tens of thousands of patient years are reassuring. Two examples are the all-BARI-RA analysis, which assessed long-term safety in more than 10,000 patient-years of exposure in multiple barcitinib rheumatoid arthritis (RA) studies, and the Corrona safety study, which assessed real-world safety in more than 2000 patient-years of tofacitinib treatment.

Other Kinase Targets
I came away thinking that JAK inhibitors are only the beginning of the kinase inhibitor race, as the human kinome has more than 500 potential targets including MAPK, PI3K, and BTK. Week 12 efficacy data from the phase II ANDES trial comparing the BTK inhibitor fenebrutinib with adalimumab and methotrexate was presented at EULAR. However, we are still several steps away from adopting drugs that target these molecules into practice, as we await further evidence of their efficacy and safety.

As always, with rare exceptions, change should and often does come iteratively. Although “a-ha” moments at these meetings are rare, they propel progress that no doubt ultimately affects clinical practice. 

Patient-Centered RA Care
Finally, I was struck by the number of discussions surrounding the role of the patient in achieving our treat-to-target goals in RA and other inflammatory conditions. We now recognize that perhaps one third of patients fail to achieve low disease states or remission in RA based on the patient global assessment. This index measures a wide variety of factors including pain, fatigue, mood, sense of empowerment, and overall happiness. We are becoming increasingly aware of the role of empathy and relationship-centered care in contributing to our patients’ well-being, and we must work to enhance these skills and teach them to the next generation of rheumatologists.

As clinicians, we are now armed with such a potent armamentarium of therapies, and we must be cautious not to overtreat. We must also enhance our capacity to understand the complaints and concerns of our patients. This has increased my interest in using biomarkers to selectively treat patients and help adjudicate cases where there remains uncertainty regarding the best approach. 

Overall, the data presented at the APLAR, JCR, and EULAR 2019 meetings and the discussions that occurred regarding patient care approaches have given me much to consider in terms of current and future therapies and how we can incorporate new therapies while remembering to keep our practice patient centered.

Your Thoughts
Join the discussion by posting a comment, or for more details on these and other key data from APLAR, JCR, and EULAR 2019, check out full conference coverage from CCO here. Review study summary slidesets or download a comprehensive slideset. Then be sure to check back soon for CME-certified Expert Analysis of the meetings from Stanley B. Cohen, MD, and Jonathan Kay, MD. 

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Supported by educational grants from
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Lilly
Sanofi Genzyme and Regeneron Pharmaceuticals

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