The Third Line Construction and Jinjiang Factory

Toleration ◽  
2018 ◽  
pp. 29-41
Author(s):  
Chao Chen
2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1672.2-1672
Author(s):  
N. Busquets-Pérez ◽  
C. Sánchez-Piedra ◽  
P. Vela-Casasempere ◽  
M. Freire-Gonzalez ◽  
C. Bohórquez ◽  
...  

Background:Ustekinumab has been efficacy and safety for psoriatic artritis in clinical trials.Objectives:To assess effectiveness, by means of drug persistence analisys, and safety of ustekinumab in patients with psoriastic arthritis in Biobadaser.Methods:BIOBADASER is the Spanish registry of biological drugs of the Spanish Society of Rheumatology and the Spanish Medicines Agency. We identified patients aged 18 years or more with psoriatic arthritis on Ustekinumab. A descriptive analysis was performed.The persistence of ustekinumab therapy was calculated with a Kaplan-Meier curve and was compared with the persistence of anti-TNF, according to line treatment. Log Rank test was used to establish a comparison. Adverse events occurring with ustekinumab are described according to year treatment.Results:One hundred and twelve patients were on ustekinumab. Most of them were on their second or third line treatment: 53.57% more than one biological therapy (BT), 19.64% second BT, 26.79% were naïve for BT. Most of them were on 45 mg dose: 88.24%. Median duration of disease at Ustekinumab initiation was 10.1 SD 7.2 years; 69.23% had peripheral arthritis; 45.24% had obesity and 39.29% were overweight; 40,6% were on prednisone and 59.82% on DMARD. The cause of discontinuation of treatment was mainly inefficacy (82.61%) and less common an adverse event (6.52%). The probability of persistence of treatment with ustekinumab was 0.83 (95% CI 0.63-0.92) at year 1, 0.79 (0.58-0.90) at year 2 and 0.79 (0.58-0.9) at year 3 when ustekinumab was prescribed as the first line treatment. The persistence decrease when ustekinumab was prescribe as a second and third treatment: being 0.53 (0.27-0.73) the first year, 0.46 (0.22-0.67) the second year and 0.46 (0.22-0.67) as a second line treatment and 0.58 (0.44-0.70) the first year, 0.33 (0.17-0.50) the second year and 0.33 (0.17-0.50) the third year as a third line treatment.The persistence was similar to anti-TNF treatment, according to line treatment. Adverse events were mainly mild (97.83%) and occurred the first year of treatment. Most of the adverse events were classified as “infections and infestations” (36.96%).Conclusion:The persistence of ustekinumab was high, being 83% at the end of the first year on treatment and 79% the second and the third year of treatment. The persistence of ustekinumab was higher when if it was the first line treatment compared as if it was used as the second o third BT option. The persistence of Ustekinumab is similar to the persistence of anti-TNF treatments in all the analyzed treatment lines (no statistically differences were found). Adverse events occurred mainly during the first year treatment. They were mainly mild adverse events and the frequency decreased within the second and third year of treatment.References:[1]Treatment with ustekinumab in a Spanish cohort of patients with psoriasis and psoriatic arthritis in daily clinical practice.Almirall M, Rodriguez J, Mateo L, Carrascosa JM, Notario J, Gallardo F. Clin Rheumatol. 2017 Feb;36(2):439-443;[2]Minimal disease activity in patients with psoriatic arthritis treated with ustekinumab: results from a 24-week real-world study.Napolitano M, Costa L, Caso F, Megna M, Scarpa R, Balato N, Ayala F, Balato A. J Clin Rheumatol. 2018 Oct;24(7):381-384;[3]Minimal Disease Activity and Patient-Acceptable Symptom State in Psoriatic Arthritis: A Real-World Evidence Study With Ustekinumab.Queiro R, Brandy A, Rosado MC, Lorenzo A, Coto P, Carriles C, Alperi M, Ballina J. Actas Dermosifiliogr. 2018 Jun 28;[4]An analysis of Drug Survival, Effectiveness, and Safety in Moderate to Severe Psoriasis Treated With Ustekinumab: An Observational Study of 69 Patients in Routine Clinical Practice.Salgüero Fernández I, Gil MH, Sanz MS, Gullón GR;Disclosure of Interests:None declared


2018 ◽  
Vol 29 ◽  
pp. viii157
Author(s):  
H. Kamiyama ◽  
Y. Yoshida ◽  
H. Yoshida ◽  
C. Kosugi ◽  
K. Ishibashi ◽  
...  

Immunotherapy ◽  
2021 ◽  
Author(s):  
Lei Song ◽  
Rengui Zhou ◽  
Xiangyong Li ◽  
Dejian Pan

Small-cell lung cancer (SCLC) is sensitive to chemoradiotherapy but remains to have a poor prognosis. In the immunotherapy era, chemotherapy combined with PD-L1 inhibitors has become a new first-line treatment option for advanced SCLC. The CheckMate 032 study combined a PD-1 blockade and a CTLA-4 inhibitor and found that this dual immunotherapy might be a positive treatment choice for SCLC. In our case, the patient with advanced SCLC received bevacizumab combined with dual immunotherapy over the third line with more than 12 months survival time. The overall survival time was 21.5 months from the start of the third-line treatment and 39 months from the time of extensive-disease SCLC diagnosis. The combination of a VEGF blockade and a dual immunotherapy in SCLC resulted in synergistic treatment effects. Therefore, bevacizumab might be a better adjuvant, either combined with chemotherapy or dual immunotherapy, for patients with persistent disease progression after undergoing immunotherapy.


2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Wei Yu ◽  
Qiaomeng Tao ◽  
Yufeng Zhang ◽  
Fengming Yi ◽  
Long Feng

Background. The most effective treatment of immune checkpoint inhibitors (ICIs) is restricted in microsatellite instability (MSI-H) subsets of advanced colorectal cancer, but MSI-H only accounts for 4-5% among them. ICIs are completely ineffective in advanced colorectal cancer patients with microsatellite stable (MSS), according to literatures published. Regorafenib is a novel tyrosine kinase inhibitor (TKIs) that could normalize tumor blood vessels by inhibiting vascular endothelial growth factor receptor and its downstream, thus improving cytotoxic T cell infiltration in tumor microenvironment, which has a synergistic effect with ICIs. Toripalimab is a type of anti-PD-1 monoclonal antibody produced by Junshi Biosciences in China. Herein, we aimed to explore the efficacy and safety of regorafenib combined with toripalimab in the third-line and beyond treatment of advanced colorectal cancer. Methods. We evaluated the outcomes of MSS patients with advanced colorectal cancer who received regorafenib combined with toripalimab in the Second Affiliated Hospital of Nanchang University from June 2019 to January 2021. These patients had previously received at least second-line treatment; the regimens were oxaliplatin and irinotecan-based chemotherapy and/or accompanied with bevacizumab or cetuximab. Thirty-three patients were treated orally with regorafenib 80 mg or 120 mg once daily for 21 days, 28 days as a cycle, combined with intravenous toripalimab until disease progression or intolerant to adverse reactions. We used the Kaplan–Meier method to estimate the rate of progression-free survival (PFS) and log-rank method to do a statistical test of the survival curve. The Cox regression model was used to analyze the influence of multiple factors on PFS. The primary endpoints were objective remission rate (ORR) and disease control rate (DCR). The secondary endpoints were the incidence of adverse reactions and median progression-free survival (mPFS). Results. The evaluation of treatment effects was assessed according to RECIST 1.1. Four patients (12.12%) got partial response, twelve patients (36.36%) experienced stable disease, and seventeen patients (51.52%) suffered progressive disease. ORR was 12.12% and DCR was 48.48%. mPFS was 113 days (95% CI: 0–272.1). In univariate analysis, patients who had previously received second-line treatment were significantly better than those who had received third-line or more treatment ( p = 0.005 ). Lung metastasis was a negative factor in combined therapy ( p = 0.032 ). Five patients without previous treatment of bevacizumab were effective. Previous treatment without bevacizumab showed a trend of effective when combination therapy ( p = 0.034 ). It was also a positive factor that the Eastern Cooperative Oncology Group performance status (ECOG) score was 0 ( p = 0.034 ). Multivariable Cox regression analysis showed the number of previous chemotherapy lines and excision of primary lesions were independent prognostic factors. The most common treatment-related adverse reactions were hand-foot syndrome (33.33%), liver dysfunction (27.27), hypothyroidism (24.24%), fever (24.24%), fatigue (21.21%), leukopenia (15.15%), hypertension (12.12%), platelet count decreased (6.06%), diarrhea (3.03%), and myocarditis (3.03%); one patient stopped treatment as myocarditis. The incidence of grade 3/4 adverse reactions was 9.09%. Conclusions. Regorafenib combined with toripalimab has a promising effect in the third-line and beyond treatment of advanced colorectal cancer. In the early use of combination therapy, excision of primary lesions can have a positive impact in regorafenib and toripalimab combination. This treatment-related adverse reactions are tolerant in combined therapy.


1998 ◽  
Vol 48 (1) ◽  
pp. 75-81 ◽  
Author(s):  
Andrew Barker

Athenaeus (637a) records these lines from the dithyramb Hymenaios, along with a number of other snippets of poetry, in the course of an inconclusive discussion about the characteristics of the instrument (if it is an instrument) called the magadis. Athenaeus had good reasons for being puzzled; the word first appeared in Greek, so far as we know, in the seventh century b.c., and its sense was already a matter of some doubt in the fourth. As to this particular fragment, even Telestes' original audience might be forgiven some bafflement in the face of the third line, on which I shall initially focus here. What can be meant by ‘the five-rodded joining of the strings’?


Mnemosyne ◽  
2004 ◽  
Vol 57 (4) ◽  
pp. 387-406 ◽  
Author(s):  
Joel Lidov

AbstractIn current commentaries and translations, the first stanza of Sappho fr. 17 is read as a prayer for Hera's presence. This understanding was created by modifying Wilamowitz's interpretation of the fragment as a dream narrative, but it depends on an improbable use of the opening word πλασιον involves an awkward third-person periphrasis for the second-person appeal, and creates insoluble difficulties of supplementation and usage in the third line. It is more fruitful to read the stanza as a deprecation of the god's anger, as in fr. 1.1-4; a suggested reading of χαλεπην ϑυελλαν (cf.Il. 21.335) gives αραταν a meaning within its normal, somewhat pejorative connotation, and allows a more plausible reconstruction of the end of line 3; attributing the source of the Atridae's distress to Hera is consistent with a number of indications of a narrative pattern in which Hera sends disruptive storms.


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