Efficacy and safety of BRAF inhibitors and anti-CTLA4 antibody in melanoma patients-real-world data.

PURPOSE: In the management of melanoma, BRAF inhibitors yield fast disease control; however, the duration of response does not last very long. Ipilimumab-an anti-CTLA4 antibody on the other hand-provides longer-lasting results of treatment but achieves less favorable responses. The aim of this study was to assess the efficacy and safety of novel drugs for advanced melanoma in daily routine practice. METHODS: A retrospective observational study was conducted on all Polish patients (1170 patients), diagnosed with advanced metastatic melanoma, treated with the following drugs: vemurafenib, dabrafenib, and ipilimumab. The antitumor efficacy of these agents was retrospectively assessed by Response Evaluation Criteria in Solid Tumors in the case of BRAF inhibitors and by Immune-Related Response Criteria in the case of ipilimumab therapy. Adverse events were assessed in relation to the morphologic parameters of blood, nephrotoxicity, and hepatotoxicity. RESULTS: The overall response to treatment with BRAF inhibitors (vemurafenib and dabrafenib) was similar with a slightly better outcome in the group treated with vemurafenib. Compared to clinical trials, the objective response rate was slightly worse for both BRAF inhibitors (30% and 42% for dabrafenib and vemurafenib, respectively), as well as the immune-related response for ipilimumab (1%). There was no significant difference in patient's response rates regardless of what lines of treatment (first, second, or next) vemurafenib was applied in. A few severe adverse events (mostly anemia and hyperbilirubinemia) were observed during treatment. CONCLUSIONS: The lack of evidence in responses observed regardless of what line of treatment vemurafenib was applied in suggests there is no clinical reason for restricting BRAF inhibitors to only the first line of therapy. Our study confirms that novel agents brought about a major advancement in the management of melanoma. In line with literature, BRAF inhibitors and ipilimumab significantly improved the antitumor response rate with manageable adverse events.

C3435T Polymorphism of the ABCB1 Gene in Polish Patients with Inflammatory Bowel Disease: A Case-Control and Meta-Analysis Study.

P-glycoprotein encoded by the ABCB1 gene constitutes a molecular barrier in the small and large bowel epithelium, and its different expression may influence susceptibility to inflammatory bowel disease (IBD). We aimed to assess the contribution of the C3435T polymorphism to disease risk in the Polish population. A total of 100 patients (50 Crohn's disease (CD), 50 ulcerative colitis (UC)) and 100 healthy controls were genotyped for the single nucleotide polymorphism (SNP) C3435T by using the PCR-RFLP method. Patients were classified on the basis of disease phenotype and the specific treatment used. A meta-analysis was carried out of our results and those from previously published Polish studies. There was no significant difference in allele and genotype frequencies in IBD patients compared with controls. For CD patients, a lower frequency of TT genotype in those with colonic disease, a lower frequency of T allele, and a higher frequency of C allele in those with luminal disease were observed, whereas for UC patients, a lower frequency of CT genotype was observed in those with left-sided colitis. A meta-analysis showed a tendency towards higher prevalence of CC genotype in UC cases. These results indicate that the C3435T variants may confer a risk for UC and influence disease behaviour.

Infliximab, adalimumab, golimumab, vedolizumab and tofacitinib in moderate to severe ulcerative colitis: comparative cost-effectiveness study in Poland.

BACKGROUND: Current management of ulcerative colitis (UC) is aimed to treat active disease and to maintain remission. For patients in whom conventional treatment is no longer effective, biological or small molecule therapy may be an option. The aim was to assess the cost-effectiveness of induction and maintenance treatment up to 1 year of UC with infliximab (IFX), adalimumab (ADA), golimumab, vedolizumab (VDZ) and tofacitinib (TFB) compared with standard of care (SoC) in Poland. METHODS: A hybrid decision tree/Markov model was used to estimate the expected costs and effects of four biologics, TFB and placebo in patients with the diagnosis of moderate to severe UC who had an inadequate response, lost response, or were intolerant to a conventional therapy. Prior exposure to anti-TNF was considered. At the beginning of the maintenance phase, the decision to continue biological therapy was determined by the achievement of response at the end of induction. Efficacy data were obtained from a network meta-analysis using placebo as the common comparator. Costs were presented in 2018 Polish zloty (PLN) and outcomes included quality-adjusted life-years (QALYs). The analysis was performed from the Polish public payer's perspective and lifetime horizon was set. RESULTS: In anti-TNF naïve, IFX and VDZ were characterized by the most favourable incremental cost-effectiveness ratios (ICURs) compared with SoC, PLN211,250.78 and PLN361,694.61/QALY (€49,589.38 and €84,904.84/QALY), respectively. In anti-TNF-exposed population the most effective treatment was TFB. Both ADA and VDZ were more effective than SoC; however, ICUR values were much above the cost-effectiveness threshold. The incorporation of biosimilars reversed the ranking of treatments in relation to the growing ICUR. CONCLUSION: Although ICUR values for all biological therapies exceeded the acceptability threshold in Poland, for anti-TNF-naïve UC patients IFX and for anti-TNF-exposed UC patients VDZ are currently the most cost-effective alternatives.

Faecal calprotectin as a diagnostic marker of inflammatory bowel disease in patients with gastrointestinal symptoms: meta-analysis.

Colonoscopy is the standard medical procedure to identify inflammatory bowel disease (IBD) in patients with gastrointestinal symptoms. Noninvasive measurement of faecal calprotectin concentration may replace colonoscopy in this indication. The study aimed to assess efficacy of faecal calprotectin as a diagnostic marker of IBD in patients with symptoms suggestive of such diagnosis. Meta-analysis of diagnostic accuracy studies was performed. Cochrane, EMBASE and MEDLINE databases were searched until December 2018. Inclusion criteria comprised experimental and observational studies, adults with gastrointestinal symptoms, calprotectin as index and colonoscopy as reference test, presence of data on/enabling the calculation of diagnostic accuracy parameters. For each study, sensitivity and specificity of faecal calprotectin were analysed as bivariate data. Nineteen studies were identified. The total number of patients was 5032. Calculated pooled sensitivity and specificity were 0.882 [95% confidence interval (CI), 0.827-0.921] and 0.799 (95% CI, 0.693-0.875), respectively. Following faecal calprotectin incorporation in the diagnostic work-up of 100 people with suspected IBD, 18 non-IBD patients will have a colonoscopy performed and one patient with the disease will not be referred for this examination. Faecal calprotectin concentration measurement is a useful screening test to rule out IBD, at the same time reducing the need for colonoscopy by 66.7%.

Survival of melanoma patients treated with novel drugs: retrospective analysis of real-world data.

PURPOSE: Recently, several new drugs have been licensed for advanced melanoma therapy, significantly changing the therapeutic landscape. Ipilimumab and vemurafenib were the first drugs that demonstrated a survival benefit over the long-standing standard therapy with dacarbazine. However, the comparative efficacy of these novel drugs has not been properly assessed yet. PATIENTS AND METHODS: We conducted a retrospective analysis of all the Polish population treated between January 2012 and October 2016 with one of the following agents: ipilimumab (IPI), vemurafenib (VEM), dabrafenib (DAB), and classic chemotherapy (CTH). The main objective was to assess the overall survival of melanoma patients treated in real-world conditions, taking into account sequences of treatment. RESULTS: We identified 3397 patients with malignant melanoma treated for the first line and the second line. Patients receiving CTH were significantly older than those treated with the novel drugs. At the same time, the population treated with immunotherapy and targeted therapy was well balanced. Overall survival was significantly better for the novel drugs compared to classic chemotherapy in both lines (for the first line, VEM vs CTH HR = 0.72, 95% CI 0.65-0.81; p < .01, and for the second line, VEM vs CTH HR = 0.78, 95% CI 0.62-0.98; p = .03; IPI vs CTH HR = 0.72, 95% CI 0.62-0.86; p < .01). There was no statistically significant difference for IPI vs VEM; however, subgroup analysis revealed superior results in the case of the CTH-IPI over BRAFi-IPI sequence. CONCLUSION: Novel drugs for melanoma provide a significant advantage in survival over classic chemotherapy. Comparative assessment of IPI and VEM indicated no difference, but only immunotherapy-treated patients achieved long-lasting results. Our data on sequential treatment indicate that immunotherapy might be a better option for the first line rather than targeted therapy, but that conclusion requires further studies of the best way to manage the treatment of melanoma patients.