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Defining response to TNF-inhibitors in rheumatoid arthritis: the negative impact of anti-TNF cycling and the need for a personalized medicine approach to identify primary non-responders.

Abstract
Current guidelines recommend treating rheumatoid arthritis (RA) patients to reach low disease activity or remission, however, most biologic-naive RA patients fail to reach treatment targets on their first biologic therapy. Approximately 90% of biologic-naive RA patients receive a tumor necrosis factor alpha inhibitor (anti-TNF) as their first biologic treatment, even though several alternative mechanism of action (MOA) therapies are approved as first-line options. After 3 months of therapy, patients may remain on anti-TNF therapy even if they fail to achieve the treatment target, mainly due to formulary structures. This means patients have to endure a second and even a third ineffective anti-TNF-called anti-TNF cycling-before changing MOA. This significantly delays patients from reaching their treatment targets. All anti-TNF drugs target the same molecular and inflammatory pathways; thus, it is not surprising that most patients who are primary non-responders to their initial anti-TNF therapy fail to achieve their treatment targets when cycled through alternative anti-TNFs. This suggests that primary non-responders should be switched to an alternative MOA therapy rather than enduring anti-TNF cycling. Avoiding anti-TNF cycling would prevent disease progression and improve quality of life for RA patients who are primary non-responders to anti-TNFs. The development of a personalized medicine approach to identify primary non-responders to anti-TNFs prior to treatment would allow significantly more patients to reach their treatment target by treating them with alternative MOA therapies as first-line therapies.
AuthorsKeith J Johnson, Helia N Sanchez, Nancy Schoenbrunner
JournalClinical rheumatology (Clin Rheumatol) Vol. 38 Issue 11 Pg. 2967-2976 (Nov 2019) ISSN: 1434-9949 [Electronic] Germany
PMID31520227 (Publication Type: Journal Article, Review)
Chemical References
  • Tumor Necrosis Factor Inhibitors
Topics
  • Arthritis, Rheumatoid (drug therapy)
  • Humans
  • Precision Medicine
  • Treatment Failure
  • Tumor Necrosis Factor Inhibitors (therapeutic use)

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