My first impression was how everyone was elated to be back in person.
My second impression was how likely DDW could be a super-spreader event, similar to the ER Meeting in New Orleans, as the majority of attendees I encountered were unmasked, despite signage encouraging masks.
I will discuss several interwoven themes related to inflammatory bowel disease (IBD).
The first relates to the logjam of agents for moderate-severe Ulcerative colitis (UC) and/or Crohn's Disease (CD) that have been available, recently released, and soon-to-be-released IL-23 blockers. An additional sphingosine one phosphate modulator, IL-23 blockers, and JAK inhibitors may not be far behind. All with only two head-to-head studies to help differentiate efficacy/safety. The “Varsity trial” in UC demonstrated improved outcomes for vedolizumab versus adalimumab at marketed doses regarding clinical remission and endoscopic improvement; there were no significant differences in steroid-free remission or adverse events. In contrast, the “Seavue study” in moderate-severe CD did not demonstrate differences between ustekinumab and adalimumab with regards to safety or the primary outcome of clinical remission after one year. Thus, when biosimilars for TNF blockers are included in the mix there are roughly 15 potential agents for moderate-severe disease without adequate means of prioritizing which drug for which patient (i.e., we really cannot personalize medications for IBD).
The next theme is “what is moderate-severe UC or CD?”. Recall that, during the introduction of TNF blockers, the FDA labeling was for “moderate-severe UC/CD with an inadequate response to conventional agents;” a two-component label for both disease activity, not severity as defined by the IOIBD, and “refractoriness” (inadequate response to). However, the FDA has modified the labeling for subsequent biologic agents (vedolizumab, ustekinumab, ozanimod, upatacitinib) to “moderate-severe disease” without the modifier of “inadequate response.” While one would think that the modified labeling would facilitate the introduction of these advanced therapies earlier in the disease — where the benefits are enhanced and the risks diminished — without the baggage of concomitant steroids and/or immune modifiers, this has not been the case. The necessity of gaining third-party approvals has hampered the early introduction of these agents despite patients presenting with symptoms, findings, and endoscopic evidence of risks for disease progression (e.g., moderate-severe severity); as the U.S. and international societies have advocated in recent guidelines and pathways.
The resulting delay or decline of access for patients with moderate-severe symptoms typically necessitates the introduction of steroids to ameliorate the symptoms of pain, bleeding and diarrhea while awaiting insurance approval. This not only adds the burden of steroid-related risks but converts the goal of treatment from clinical/endoscopic/histologic remissions to the additional necessity for steroid-free remissions, another hurdle to the safety and quality of life for patients already confronted with managing chronic disease.
So, my final theme is “access versus accessibility.” While walking through the exhibit hall, most pharmaceutical booths emphasized the high (higher or highest) level of “access” for patients, the limitations of third-party approvals typically require patients to have failed conventional therapies. A burden on patients and providers that goes beyond FDA approvals! The delay in access goes beyond the requisite for “refractory disease.” But, the processes of authorizations/appeals/re-authorizations are cumbersome and result in morbidity while initiating therapy and risks of loss of response by delays in re-approvals for maintenance therapy and/or development of immunogenicity with biologics due to dose-interruptions. Thus, while patients may have access to an approved therapy based on our shared decision making, the delays in accessibility is what hampers the optimal care for our patients.
Dr. Hanauer is employed by Northwestern University. He has received grants and consulting fees from Abbvie, Allergan, Amgen, Arena, Boehringer-Ingelheimt, BMS, Celgene, Celtrion, Genentech, Gilead, GSK, Gossamer, Lilly, Merck, Novartis, Pfizer, Progenity, Prometheus, Protagonist, Receptos, Salix, Samsungbioepis, Seres Therapeutics, Takeda, TTL Pharma, UCB, and VHsquared.
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