Systematic Literature Review of Real-World Evidence on Dose Escalation and Treatment Switching in Ulcerative Colitis.

Background: Currently approved biologic therapies for moderate-to-severe ulcerative colitis have well-established efficacy. However, many patients fail to respond or lose response, leading to dose escalation or treatment switching. Objective: We sought to identify real-world evidence on dose escalation and treatment switching and associated clinical and economic outcomes among adults with ulcerative colitis treated with infliximab, adalimumab, golimumab, vedolizumab, ustekinumab, or tofacitinib. Methods: We conducted a systematic search of Embase, MEDLINE (up to 26 August 2020), and conference proceedings (2017-2020) for studies in adults with ulcerative colitis to assess clinical response and remission, colectomy, adverse events, and economic outcomes related to dose escalation and treatment switching. Results: In 56 studies, dose escalation and treatment switching involving infliximab and/or adalimumab were most frequently investigated. Rates of clinical response after dose escalation were 20-95% (1.8-36 months), clinical remission rates were 10-94% (1.8-36 months), colectomy rates were 0-33% (12-38 months), and adverse event rates were 0-18%. Treatment switching rates in 21 studies were 4-70% over 3-62 months, with switch due to loss of response rates of 4-35% over 12-62 months (7 studies). Up to 35% of patients underwent colectomy 12-120 weeks after switching, and 13-38% experienced adverse events. Data relating to economic outcomes were limited to tumor necrosis factor inhibitors, but demonstrated increased direct costs associated with both dose escalation and treatment switching. Conclusion: Dose escalation and treatment switching are common with existing therapies. However, clinical response and remission rates vary, and a proportion of patients fail to achieve optimal clinical and economic outcomes. This highlights the need for more efficacious and durable treatments for patients with moderate-to-severe ulcerative colitis.

Endoscopic mucosal healing and histologic remission in ulcerative colitis: a systematic literature review of clinical, quality-of-life and economic outcomes.

OBJECTIVE: This systematic literature review (SLR) assessed the effects of endoscopic mucosal healing and histologic remission on clinical, quality-of-life (QoL), and economic outcomes in adults with ulcerative colitis (UC) in the real-world setting. METHODS: Literature searches of Embase and MEDLINE (6 July 2020) and conference proceedings (2017-2020) were performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Eligible studies included adults with UC with documented endoscopic mucosal healing or histologic remission. Clinical, QoL, and economic outcomes were extracted and narratively synthesized. RESULTS: Of 1603 studies screened, 25 met eligibility criteria and collectively included 2813 patients (mean age: 34-60 years). The most commonly reported indices were Mayo endoscopic score (MES) for endoscopic mucosal healing (n = 22, 88%) and Geboes score (n = 5, 20%) for histologic outcomes. The most frequently reported clinical outcome was relapse-free survival (n = 15, 60%). Less commonly reported outcomes were avoidance of colectomy (n = 5, 20%), hospitalization (n = 4, 16%), clinical remission (n = 4, 16%), and steroid-free clinical remission (n = 3, 12%). Most studies reported relapse-free survival rates up to 50% over 6-48 months of follow-up in endoscopic mucosal healing cohorts. Studies reporting results by MES demonstrated higher relapse-free survival rates among patients with MES 0 than with MES 1 (32%-100% vs 26%-86%, respectively). Similarly, patients with histologic remission had better relapse-free survival rates over 12-24 months of follow-up compared with those without histologic remission (72%-91% vs 40%-63%, respectively). Rates of clinical remission, steroid-free remission, hospitalization, and colectomy avoidance were also better among patients with endoscopic mucosal healing and histologic remission. Two studies examining QoL reported endoscopic mucosal healing was associated with improved QoL. No study reported economic outcomes. CONCLUSIONS: This SLR demonstrated consistent evidence of improved clinical outcomes among UC patients with endoscopic mucosal healing and histologic remission.

Ulcerative colitis (UC) is a chronic, relapsing disease characterized by inflammation of the mucous membranes lining the rectum and colon. While medical management has traditionally focused on lessening UC symptoms, there is growing recognition that the reduction of underlying inflammation visible endoscopically (called endoscopic mucosal healing) or microscopically (called histologic remission) can be an objective indicator of disease improvement. This research is the first systematic literature review to assess the effects of endoscopic mucosal healing and histologic remission on clinical, quality-of-life (QoL), and economic outcomes in adults with UC in the real-world setting. We included studies in adults with UC who had mucosal healing or histologic remission and analyzed clinical, QoL, and economic outcomes using a technique called narrative synthesis. Twenty-five of 1603 studies screened met our eligibility criteria for inclusion in the analysis. In most studies, over 50% of patients with endoscopic mucosal healing did not relapse during follow-up, with better relapse-free survival rates reported among patients with a Mayo endoscopic scores of 0 than among those with a score of 1. Likewise, patients with histologic remission had higher relapse-free survival rates than those without histologic remission. Rates of clinical remission, steroid-free remission, hospitalization, and colectomy avoidance were better among patients with mucosal healing and/or histologic remission. Two studies also reported better QoL outcomes. Our findings suggest that endoscopic mucosal healing or histologic remission is associated with improved clinical and QoL outcomes. While more information is required, these measures should be considered important when making therapeutic decisions for patients with UC.

Use of the Functional Assessment of Cancer Therapy--anemia in persons with myeloproliferative neoplasm-associated myelofibrosis and anemia.

BACKGROUND: Anemia is common in myeloproliferative neoplasm (MPN)-associated myelofibrosis. The Functional Assessment of Cancer Therapy (FACT) measurement system is a patient-reported outcomes instrument that documents symptoms of the diverse aspects of cancer treatment. One FACT version, FACT-Anemia (FACT-An), documents symptoms of anemia related to cancer. The FACT-An has been validated in diverse cancer populations, but not in MPN-associated myelofibrosis. OBJECTIVE: Our aim was to evaluate the relationship between anemia response to therapy with pomalidomide with or without corticosteroids and patient-reported outcomes using the FACT-An instrument. METHODS: Data were obtained from a Phase II, randomized, double-blind Bayesian pick-the-winner trial of prednisone and pomalidomide in patients with MPN-associated myelofibrosis and anemia (red blood cell-transfusion dependence). Details of the study, including definitions of anemia, anemia response, red blood cell-transfusion, red blood cell-transfusion dependence, and red blood cell-transfusion independence, are reported. Change in quality of life from randomization to the last cycle of therapy was evaluated using the FACT-An Physical Well Being, Functional Well Being, Trial Outcome Index, and Anemia domains. Clinically important differences were used to determine the smallest difference in scores that patients perceived as beneficial in the FACT-An domains of interest. Patients were classified as meeting clinically important differences for responsiveness if their change score from baseline was >1 SEM, indicating improvement. RESULTS: Eighty-five patients were studied. Thirty-one patients (37%) were classified as anemia responders by prospectively defined criteria. Across all FACT-An domains, anemia responders showed greater improvement in Physical Well Being, Functional Well Being, and Trial Outcome Index scores than did nonresponders. This improvement began at the second 28-day cycle of therapy and was sustained. CONCLUSIONS: We show a correlation between anemia response and improved quality of life measured by the FACT-An instrument in patients with MPN-associated myelofibrosis and anemia.