first line therapy
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2022 ◽  
Vol 19 (1) ◽  
Author(s):  
Nolwenn Hall ◽  
Clotilde Allavena ◽  
Christine Katlama ◽  
Alexandra Jobert ◽  
Jean-Michel Molina ◽  
...  

Abstract Background Raltegravir (RAL) has favorable tolerability and safety profile, with few and manageable drug interactions. The use of RAL 1200 mg once daily (qd) for first-line therapy is well established. We assessed efficacy and safety of RAL 1200 mg qd, as part of triple combined antiretroviral therapy (cART), for maintenance strategy. Methods The QDISS trial (NCT03195452) was a 48-week multicenter, single-arm, open-label study designed to evaluate the ability of 2 NRTIs + RAL 1200 mg qd to maintain virological suppression in HIV-1 infected subjects on a stable cART with 2 NRTIs and a third agent for at least 6 months. The primary endpoint was the proportion of participants with HIV-1 RNA < 50 copies/mL at week 24, by the FDA snapshot algorithm. Results Of 100 participants 91% maintained viral suppression (95% CI: 83.6–95.8) at week 24 and 89% (81.2–94.4) at week 48. At week 24, there was one virological failure, without emergence of resistance-associated mutation and 10 participants had discontinued, 4 because of adverse events (AEs). Over 48 weeks, 7 AEs of grade 3–4 were reported, one possibly study-drug related (spontaneous abortion). BMI remained stable regardless of previous therapy or baseline BMI category. Over 48 weeks, total cholesterol (p = 0.023) and LDL-cholesterol (p = 0.009) decreased, lifestyle and ease subscale significantly improved (p = 0.04). The quality of life and Patients Reported Outcomes (PROs) also improved at W12 (p = 0.007). Conclusion RAL 1200 mg qd as part of a maintenance triple therapy showed a high efficacy in virologically suppressed HIV-1 infected subjects, with good safety profile and improved lipid profile and patient reported outcomes. Trial registration: Clinical trials.gov NCT03195452 and EudraCT 2016-003702-13.


Haematologica ◽  
2022 ◽  
Author(s):  
Carol Moreno ◽  
Richard Greil ◽  
Fatih Demirkan ◽  
Alessandra Tedeschi ◽  
Bertrand Anz ◽  
...  

iLLUMINATE is a randomized, open-label phase 3 study of ibrutinib plus obinutuzumab (n=113) versus chlorambucil plus obinutuzumab (n=116) as first-line therapy for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma. Eligible patients were aged ≥65 years, or


2022 ◽  
Vol 12 ◽  
Author(s):  
Francesca Racca ◽  
Gaia Pellegatta ◽  
Giuseppe Cataldo ◽  
Edoardo Vespa ◽  
Elisa Carlani ◽  
...  

Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease of the esophagus characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation, whose incidence is rising. It significantly affects patients’ quality of life and, if left untreated, results in fibrotic complications. Although broad consensus has been achieved on first-line therapy, a subset of patients remains non-responder to standard therapy. The pathogenesis of EoE is multifactorial and results from the complex, still mostly undefined, interaction between genetics and intrinsic factors, environment, and antigenic stimuli. A deep understanding of the pathophysiology of this disease is pivotal for the development of new therapies. This review provides a comprehensive description of the pathophysiology of EoE, starting from major pathogenic mechanisms (genetics, type 2 inflammation, epithelial barrier dysfunction, gastroesophageal reflux, allergens, infections and microbiota) and subsequently focusing on the single protagonists of type 2 inflammation (involved cells, cytokines, soluble effectors, surface proteins and transcription factors) that could represent present and future therapeutic targets, while summarizing previous therapeutic approaches in literature.


2022 ◽  
Vol 12 ◽  
Author(s):  
Claudia Pivonello ◽  
Roberta Patalano ◽  
Mariarosaria Negri ◽  
Rosa Pirchio ◽  
Annamaria Colao ◽  
...  

Pituitary neuroendocrine tumors (PitNET) are commonly benign tumors accounting for 10-25% of intracranial tumors. Prolactin-secreting adenomas represent the most predominant type of all PitNET and for this subtype of tumors, the medical therapy relies on the use of dopamine agonists (DAs). DAs yield an excellent therapeutic response in reducing tumor size and hormonal secretion targeting the dopamine receptor type 2 (D2DR) whose higher expression in prolactin-secreting adenomas compared to other PitNET is now well established. Moreover, although DAs therapy does not represent the first-line therapy for other PitNET, off-label use of DAs is considered in PitNET expressing D2DR. Nevertheless, DAs primary or secondary resistance, occurring in a subset of patients, may involve several molecular mechanisms, presently not fully elucidated. Dopamine receptors (DRs) expression is a prerequisite for a proper DA function in PitNET and several molecular events may negatively modify DR membrane expression, through the DRs down-regulation and intracellular trafficking, and DR signal transduction pathway. The current mini-review will summarise the presently known molecular events that underpin the unsuccessful therapy with DAs.


2022 ◽  
Vol 12 ◽  
Author(s):  
George N. Dalekos ◽  
Pinelopi Arvaniti ◽  
Nikolaos K. Gatselis ◽  
Anna Samakidou ◽  
Stella Gabeta ◽  
...  

Background/AimsAs previous real-world studies and meta-analyses have shown that mycophenolate mofetil (MMF) might have better efficacy than azathioprine (AZA) in autoimmune hepatitis (AIH), we conducted a propensity matching study to assess the efficacy and safety of MMF vs. AZA.MethodsAll 126 consecutive treatment-naive adult AIH patients, diagnosed and followed in our department since 2016, were included. Patients received prednisolone 0.5–1 mg/kg/day plus either AZA 1–2 mg/kg/day or 1.5–2 g/day MMF. The tapering of prednisolone was identical between groups.ResultsAfter propensity matching score and adjustment for known factors affecting response to treatment and outcome, 64 patients were included in the study (MMF = 32 and AZA = 32). Rates of non-response, complete biochemical response (CBR) at 6 and 12 months, and prednisolone withdrawal (6 months, 12 months, and end of follow-up) were identical between groups. However, MMF treatment was significantly associated with CBR at the end of follow-up [odds ratio (OR) 11.259; 95% CI: 1.3–97.4, p = 0.028]. AZA patients were more prone to stop treatment due to AZA intolerance/insufficient response (p = 0.0001). At the end of follow-up, the overall efficacy of each schedule was also significantly higher in the MMF group compared to the AZA group (p = 0.0001).ConclusionWe showed for the first time in a propensity matching study that MMF can be used as first-line therapy in AIH as attested by the significantly higher CBR at end of follow-up compared to AZA. Whether this better efficacy is also associated with higher histological remission rates and sustained CBR off immunosuppression needs further evaluation.


2022 ◽  
Vol 29 (1) ◽  
Author(s):  
Diki Arma Duha ◽  
Hendy Mirza

Objective: Adreno cortical carcinoma (ACC) is a rare malignancy. Currently, surgical resection offers the best chance of cure with localized tumor. Multimodal therapy including systemic chemotherapy and radiation therapy are often required for locally advanced and metastatic disease aims to decrease these high recurrence rates. Case(s) presentation: A 42-year-old male patient was referred from internist due to mass in left adrenal. Solid mass with calcification on left adrenal gland within size 9 x 11.8 x 11.5 cm was found in MSCT. We performed complete surgical resection (adrenalectomy), and results from pathology anatomy was ACC functional T2N1M0 (stage 3). The patient was planned eight times chemotherapy with etoposide and carboplatin, but he decided to stop the treatment after six times due to no constitutional complaint. We found no residual mass on follow up six months after operation and patient demonstrated a good clinical outcome after one year. Discussion: We perform open adrenalectomy and after surgery mitotane plus etoposide, cisplatin, doxorubicin (EDP) administered as first-line therapy but we only did chemotherapy with etoposide and carboplatin because mitotane was not covered by patient insurance. We chose to not perform radiation therapy due to lesser benefit of adjuvant radiotherapy as evidenced by many studies in term of recurrence-free survival and overall survival. Conclusion: In our case, adreno cortical carcinoma treated with open adrenalectomy combined with 6 times chemotherapy used etoposide and carboplatin demonstrated a good clinical outcome after 1 year.


2022 ◽  
Vol 12 ◽  
Author(s):  
Qiao Liu ◽  
Zhen Zhou ◽  
Xia Luo ◽  
Lidan Yi ◽  
Liubao Peng ◽  
...  

Objective To compare the cost-effectiveness of the combination of pembrolizumab and chemotherapy (Pembro+Chemo) versus pembrolizumab monotherapy (Pembro) as the first-line treatment for metastatic non-squamous and squamous non-small-cell lung cancer (NSCLC) with PD-L1expression ≥50%, respectively, from a US health care perspective.Material and Methods A comprehensive Makrov model were designed to compare the health costs and outcomes associated with first-line Pembro+Chemo and first-line Pembro over a 20-years time horizon. Health states consisted of three main states: progression-free survival (PFS), progressive disease (PD) and death, among which the PFS health state was divided into two substates: PFS while receiving first-line therapy and PFS with discontinued first-line therapy. Two scenario analyses were performed to explore satisfactory long-term survival modeling.Results In base case analysis, for non-squamous NSCLC patients, Pembro+Chemo was associated with a significantly longer life expectancy [3.24 vs 2.16 quality-adjusted life-years (QALYs)] and a substantially greater healthcare cost ($341,237 vs $159,055) compared with Pembro, resulting in an ICER of $169,335/QALY; for squamous NSCLC patients, Pembro+Chemo was associated with a slightly extended life expectancy of 0.22 QALYs and a marginal incremental cost of $3,449 compared with Pembro, resulting in an ICER of $15,613/QALY. Our results were particularly sensitive to parameters that determine QALYs. The first scenario analysis yielded lower ICERs than our base case results. The second scenario analysis founded Pembro+Chemo was dominated by Pembro.Conclusion For metastatic non-squamous NSCLC patients with PD-L1 expression ≥50%, first-line Pembro+Chemo was not cost-effective when compared with first-line Pembro. In contrast, for the squamous NSCLC patient population, our results supported the first-line Pembro+Chemo as a cost-effective treatment. Although there are multiple approaches that are used for extrapolating long-term survival, the optimal method has yet to be determined.


2022 ◽  
Vol 11 (1) ◽  
pp. 250
Author(s):  
Martina Haas ◽  
Ewgeni Jakubovski ◽  
Katja Kunert ◽  
Carolin Fremer ◽  
Nadine Buddensiek ◽  
...  

Comprehensive Behavioral Intervention for Tics (CBIT) is considered a first-line therapy for tics. However, availability of CBIT is extremely limited due to a lack of qualified therapists. This study is a multicenter (n = 5), randomized, controlled, observer-blind trial including 161 adult patients with chronic tic disorders (CTD) to provide data on efficacy and safety of an internet-delivered, completely therapist-independent CBIT intervention (iCBIT Minddistrict®) in the treatment of tics compared to placebo and face-to-face (f2f) CBIT. Using a linear mixed model with the change to baseline of Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) as a dependent variable, we found a clear trend towards significance for superiority of iCBIT (n = 67) over placebo (n = 70) (−1.28 (−2.58; 0.01); p = 0.053). In addition, the difference in tic reduction between iCBIT and placebo increased, resulting in a significant difference 3 (−2.25 (−3.75; −0.75), p = 0.003) and 6 months (−2.71 (−4.27; −1.16), p < 0.001) after the end of treatment. Key secondary analysis indicated non-inferiority of iCBIT in comparison to f2f CBIT (n = 24). No safety signals were detected. Although the primary endpoint was narrowly missed, it is strongly suggested that iCBIT is superior compared to placebo. Remarkably, treatment effects of iCBIT even increased over time.


2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Shoujin Cao ◽  
Tianshi Lyu ◽  
Zeyang Fan ◽  
Haitao Guan ◽  
Li Song ◽  
...  

Abstract Background/aim Recent studies have suggested that periportal location of percutaneous radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is considered as one of the independent risk factors for local tumor progression (LTP). However, the long-term therapeutic outcomes of percutaneous RFA as the first-line therapy for single periportal HCCand corresponding impacts on tumor recurrence or progression are still unclear. Materials and methods From February 2011 to October 2020, a total of 233 patients with single nodular HCC ≤ 5 cm who underwent RFA ± transarterial chemoembolization (TACE) as first-line therapy was enrolled and analyzed, including 56 patients in the periportal group and 177 patients in the nonperiportal group. The long-term therapeutic outcomes between the two groups were compared, risk factors of tumor recurrence or progression were evaluated. Results The LTP rates at 1, 3, and 5 years were significantly higher in the periportal group than those in the nonperiportal group (15.7, 33.7, and 46.9% vs 6.0, 15.7, and 28.7%, respectively, P = 0.0067). The 1-, 3- and 5-year overall survival (OS) rates in the periportal group were significantly worse than those in the nonperiportal group (81.3, 65.1 and 42.9% vs 99.3, 90.4 and 78.1%, respectively, P<0.0001). In the subgroup of single HCC ≤ 3 cm, patients with periportal HCC showed significantly worse LTP P = 0.0006) and OS (P<0.0001) after RFA than patients with single nonperiportal HCC; The univariate and multivariate analyses revealed that tumor size, periportal HCC and AFP ≥ 400ug/ml were independent prognostic factors for tumor progression after RFA. Furthermore, patients with single periportal HCC had significantly higher risk for IDR(P = 0.0012), PVTT(P<0.0001) and extrahepatic recurrence(P = 0.0010) after RFA than those patients with single nonperiportal HCC. . Conclusion The long-term therapeutic outcomes of RFA as the first-line therapy for single periportal HCC were worse than those for single nonperiportal HCC, an increased higher risk of tumor recurrence or progression after RFA was significantly associated with periportal HCC.


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