Schwartz, David A.

INTRODUCTION: Advanced therapies infrequently achieve complete fistula closure in patients with Crohn's disease (CD). The primary objective of the STOMP2 clinical trial was to determine whether the implantable autologous cell therapy AVB-114 is effective in inducing remission of persistent Crohn's perianal fistulas versus standard of care. METHODS: Eligible patients had a single perianal fistula tract and had failed previous treatment or had documented medication intolerance to biologic or conventional CD therapy. All enrolled subjects underwent surgical fistula optimization and adipose tissue biopsy collection (to manufacture AVB-114) followed by 1:1 randomization to either standard of care (repeat fistula optimization including seton replacement) or AVB-114 implantation. The primary end point was combined fistula remission at 36 weeks, defined as closure of the external opening, no drainage of fluid despite gentle finger compression, and no collections >2 cm in at least 2 of the 3 dimensions on MRI. RESULTS: Subjects at 14 US sites were equally randomized to SoC (N = 24) or AVB-114 (N = 24). Week 36 combined remission was 8.3% and 45.8% for subjects randomized to SoC and AVB-114, respectively (38% difference, 95% CI 11%–60%; P = 0.0078). At week 36, MRI revealed no subjects with collections >2 cm, radiological improvement (≥50% decrease in the Magnetic Resonance Novel Index for Fistula Imaging in Crohn's Disease (MAGNIFI-CD) score from baseline) in 1 SoC subject and 3 AVB-114 subjects, and radiological healing (complete resolution of T2-weighted hyperintensity in fistula tract) in 2 SoC subjects and 5 AVB-114 subjects. Through week 36, there were 40 and 56 treatment emergent adverse events for SoC and AVB-114, respectively. There were no serious treatment emergent adverse events in the AVB-114 group through week 36. DISCUSSION: A significantly higher proportion of patients treated with AVB-114 achieved combined remission vs SoC, and the treatment was well tolerated. These data support the safety and efficacy of AVB-114 in persistent Crohn's perianal fistulas.

Abstract Background The STOMP2 trial sought to determine whether the implantable autologous cell therapy AVB-114 is an effective add-on therapy for patients with persistent Crohn’s perianal fistulas. The trial design incorporated wait-list controlled (WLC) elements, allowing eligible control group subjects who completed the 9 mo primary endpoint visit in Part 1 to request AVB-114 treatment in Part 2 and strengthen the evaluation of AVB-114’s safety and effectiveness. Methods Eligible patients had a single perianal fistula tract and had failed prior treatment or had documented medication intolerance to biologic or conventional Crohn’s disease therapy. Subjects at 14 U.S. sites were randomized 1:1 to either standard of care (SoC; fistula optimization including seton placement) or AVB-114 implantation. The primary endpoint was combined fistula remission at 9 mo, defined as no collections >2cm on MRI, visual closure of the external opening, and no drainage of fluid despite gentle finger compression. A logistic regression time from exposure model through 9 mo utilized complete Part 1 data and all available Part 2 data to estimate combined AVB-114 effectiveness. Results Part 1 combined remission (using Non-Responder Imputation) was 8.3% (2/24) for SoC and 45.8% (11/24) for AVB-114 (38% difference, 95% CI 11 – 60%, post-hoc p-value of 0.0078). Twenty SoC subjects were treated with AVB-114 in Part 2. Four of the 9 Part 2 subjects with 9 mo combined remission data available were in combined fistula remission (44.4%). No subjects failed 9 mo radiological remission (first component of the primary endpoint), thus clinical remission (composite of the latter two components) was equivalent to combined remission. AVB-114 clinical remission in Part 1 and Part 2 to-date were similar, and when combined provided narrower estimates with the same coverage (Figure 1). Mean (SD) 9 mo perianal disease activity index (PDAI) scores for SoC, Part 1 AVB-114, and Part 2 AVB-114 were 5.0 (2.6), 4.1 (2.9), and 3.8 (3.5), respectively. Lower 9 mo scores and decreases from baseline were independently associated with an increased probability of clinical remission. Two serious treatment-emergent adverse events (TEAEs; pseudopolyposis and proctalgia) occurred, with the latter attributed to AVB-114. Non-serious product related TEAE were predominantly related to postoperative perianal pain. Two grade 2 (moderate) AEs of cellulitis and abdominal wall abscess were attributed to adipose tissue collection. Conclusion Both the randomized and combined (all-treated) analyses demonstrated substantial AVB-114 effectiveness through 9 mo in this challenging patient population. AEs were anticipated, and generally mild and infrequent. Conflict of interest: Schwartz, David: 1) Abbvie: consultant 2) Janssen: Consultant 3) Takeda: Consultant 4) Avbios- consultant 5) Olympus- consultant Dozois, Eric: TBD Ehman, Eric: TBD Faubion, William: TBD Hudesman, David: Consultant: Avalo, Abbvie, Abivax, Biocon, BMS, CorEvitas, Eli Lilly, Johnson and Johnson, Pfizer, Prometheus, Sanofi, Takeda, Fresenius Kabi Research Support: Pfizer and Johnson and Johnson Espen, Benjamin: employee of Avobis Bio LLC Pabla, Baldeep: Astellas, J & J - Advisory Board Prometheus - Speaker Eli Lilly - Speaker Papadakis, Konstantinos: TBD

The NCCN Guidelines for Head and Neck Cancers address tumors arising in the oral cavity (including mucosal lip), pharynx, larynx, and paranasal sinuses, as well as occult primary cancer, salivary gland cancer, and mucosal melanoma (MM). The specific site of disease, stage, and pathologic findings guide treatment (eg, the appropriate surgical procedure, radiation targets, dose and fractionation of radiation, indications for systemic therapy). The NCCN Head and Neck Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding management of nasopharynx cancer and ongoing research in this area.

The NCCN Guidelines for Head and Neck Cancers address tumors arising in the oral cavity (including mucosal lip), pharynx, larynx, and paranasal sinuses. Occult primary cancer, salivary gland cancer, and mucosal melanoma (MM) are also addressed. The specific site of disease, stage, and pathologic findings guide treatment (eg, the appropriate surgical procedure, radiation targets, dose and fractionation of radiation, indications for systemic therapy). The NCCN Head and Neck Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding management of HPV-positive oropharynx cancer and ongoing research in this area.

Abstract Background & Aims Crohn’s disease (CD) is a lifelong illness with substantial morbidity, although new therapies and treatment paradigms have been developed. We provide guidance for treatment of ambulatory patients with mild to severe active luminal CD. Methods We performed a systematic review to identify published studies of the management of CD. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a group of specialists. Results The consensus includes 41 statements focused on 6 main drug classes: antibiotics, 5-aminosalicylate, corticosteroids, immunosuppressants, biologic therapies, and other therapies. The group suggested against the use of antibiotics or 5-aminosalicylate as induction or maintenance therapies. Corticosteroid therapies (including budesonide) can be used as induction, but not maintenance therapies. Among immunosuppressants, thiopurines should not be used for induction, but can be used for maintenance therapy for selected low-risk patients. Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD. Biologic agents, including tumor necrosis factor antagonists, vedolizumab, and ustekinumab, were recommended for patients failed by conventional induction therapies and as maintenance therapy. The consensus group was unable to clearly define the role of concomitant immunosuppressant therapies in initiation of treatment with a biologic agent. Conclusions Optimal management of CD requires careful patient assessment, acknowledgement of patient preferences, evidence-based use of existing therapies, and thorough assessment to define treatment success.

Abstract Electronic medical records (EMRs) have gained widespread use in clinical practice and by default serve as a large patient database with potential for use in clinical research. Although there remains significant interest in leveraging EMRs for research purposes, extraction of data has proven to be complex and with insufficient accuracy. We describe the limitations of an EMR in our attempt to conduct a seemingly simple study aimed at validating variables identified in the PRECiSE 3, a 7-year open label safety and efficacy study of certolizumab pegol in Crohn’s disease that identified clinical factors that predicted both short- and long-term efficacy. A multicenter, retrospective cohort study from 8 academic and large community practices was performed, and data were collected from each respective EMR. Significant challenges with reliable capture of key data elements were encountered, and overall a screen fail rate of 91.8% across all sites was seen. We describe these challenges and potential future directions to work together to advance accuracy and implementation of the use of EMRs in inflammatory bowel disease.

SUMMARYBackgroundClinical factors were previously identified as predictors of short‐term treatment efficacy in Crohn's disease (CD). The PRECiSE 3 (P3) 7‐year trial provides an opportunity to study predictors of short‐ and long‐term clinical remission among CD patients treated with certolizumab pegol (CZP).AimTo identify factors that influence long‐term remission of CD with CZP treatment.MethodsPatients who had completed placebo‐controlled studies (PRECiSE 1/PRECiSE 2, P1/P2) enrolled in P3 and received open‐label CZP 400 mg every 4 weeks up to 7 years. Baseline predictors included, but were not limited to, smoking status, disease duration, prior inflammatory bowel disease (IBD) surgery, Harvey–Bradshaw Index (HBI), albumin, haematocrit and CZP exposure; association with time to initial remission (HBI ≤4) was tested for patients who received CZP in P1/P2; time to loss of remission/frequency of maintenance of remission was also tested. Univariate analyses and multivariate Cox or logistic regression models were used.ResultsPredictors for initial remission (N = 377) included age, haematocrit, prior IBD surgery and entry HBI (P < 0.05 for all). Predictors for loss of remission (N = 437) included HBI, serum albumin concentration, haematocrit, smoking status and exposure. Predictors of maintenance of remission (N = 437) included haematocrit, IBD surgery, HBI, disease duration, serum albumin concentration and exposure. Significant predictors were confirmed with stepwise multivariate regression models.ConclusionsThese analyses identified several influential parameters for short‐and long‐term remission of Crohn's disease with certolizumab pegol treatment. The data yield valuable hypotheses regarding factors that influence certolizumab pegol treatment. More investigation is needed.(ClinicalTrials.gov identifier NCT00552058).