Acceptable safety profile for long-term methotrexate in children

1996 ◽  
Vol &NA; (623) ◽  
pp. 6
Author(s):  
&NA;
Keyword(s):  
Safety Profile ◽  
Acceptable Safety Profile

scholarly journals Long-term efficacy and safety of cladribine (2-CdA) in adult patients with mastocytosis

Blood ◽  
2015 ◽  
Vol 126 (8) ◽  
pp. 1009-1016 ◽  
Author(s):  
Stéphane Barete ◽  
Olivier Lortholary ◽  
Gandhi Damaj ◽  
Isabelle Hirsch ◽  
Marie Olivia Chandesris ◽  
...  
Keyword(s):  
Effective Treatment ◽  
Safety Profile ◽  
Systemic Mastocytosis ◽  
Adult Patients ◽  
Efficacy And Safety ◽  
Acceptable Safety Profile ◽  
Key Points ◽  
Cutaneous Mastocytosis ◽  
Indolent Systemic Mastocytosis

Key Points 2-CdA is an effective treatment with a long-term acceptable safety profile in patients with mastocytosis. 2-CdA is effective and safe in indolent systemic mastocytosis and cutaneous mastocytosis refractory to multiple symptomatic therapies.

670 Long-term results of interstin therapy for voiding disorders demonstrate sustained efficacy and acceptable safety profile

2004 ◽  
Vol 3 (2) ◽  
pp. 170 ◽  
Author(s):  
P. Van Kerrebroeck ◽  
A. Van Voskuilen ◽  
A. Lycklama ◽  
A.A. Nyeholt ◽  
H. Dijkema ◽  
...  
Keyword(s):  
Safety Profile ◽  
Long Term Results ◽  
Acceptable Safety Profile ◽  
Sustained Efficacy ◽  
Voiding Disorders

Long-term cariprazine treatment for the prevention of relapse in patients with schizophrenia: A randomized, double-blind, placebo-controlled trial

2020 ◽  
pp. 27-37
Author(s):  
Suresh Durgam ◽  
Willie Earley ◽  
Rui Li ◽  
Dayong Li ◽  
Kaifeng Lu ◽  
...  
Keyword(s):  
Safety Profile ◽  
Relapse Prevention ◽  
Controlled Trial ◽  
Fixed Dose ◽  
Open Label ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Randomized Controlled ◽  
Time To Relapse

Cariprazine, a dopamine D3/D2 receptor partial agonist with preference for D3 receptors, has demonstrated efficacy in randomized controlled trials in schizophrenia. This multinational, randomized, double-blind, placebo-controlled, parallel-group study evaluated the efficacy, safety, and tolerability of cariprazine for relapse prevention in adults with schizophrenia; total study duration was up to 97 weeks. Schizophrenia symptoms were treated/stabilized with cariprazine 3—9 mg/d during 20-week open-label treatment consisting of an 8-week, flexible-dose run-in phase and a 12-week fixed-dose stabilization phase. Stable patients who completed open-label treatment could be randomized to continued cariprazine (3, 6, or 9 mg/d) or placebo for double-blind treatment (up to 72 weeks). The primary efficacy parameter was time to relapse (worsening of symptom scores, psychiatric hospitalization, aggressive/violent behavior, or suicidal risk); clinical measures were implemented to ensure safety in case of impending relapse. A total of 264/765 patients completed open-label treatment; 200 eligible patients were randomized to double-blind placebo (n = 99) or cariprazine (n = 101). Time to relapse was significantly longer in cariprazine — versus placebo-treated patients (P = .0010, log-rank test). Relapse occurred in 24.8% of cariprazine- and 47.5% of placebo-treated patients (hazard ratio [95% CI] = 0.45 [0.28, 0.73]). Akathisia (19.2%), insomnia (14.4%), and headache (12.0%) were reported in ≥ 10% of patients during open-label treatment; there were no cariprazine adverse events ≥ 10% during double-blind treatment. Long-term cariprazine treatment was significantly more effective than placebo for relapse prevention in patients with schizophrenia. The long-term safety profile in this study was consistent with the safety profile observed in previous cariprazine clinical trials. ClincalTrials.gov identifier: NCT01412060. Key words: schizophrenia; cariprazine; long-term treatment; relapse prevention; randomized controlled trial; oral antipsychotics

scholarly journals O09 Safety profile of baricitinib for the treatment of RA up to 8.4 years: an updated integrated safety analysis

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Kevin L Winthrop ◽  
Tsutomu Takeuchi ◽  
Gerd Burmester ◽  
Walter Deberdt ◽  
Douglas Schlichting ◽  
...  
Keyword(s):  
Safety Profile ◽  
Incidence Rates ◽  
Janus Kinase ◽  
Major Adverse Cardiovascular Events ◽  
Stock Ownership ◽  
Research Support ◽  
Vein Thrombosis ◽  
Non Melanoma Skin Cancer ◽  
Deep Vein

Abstract Background/Aims  Baricitinib (BARI) is an oral selective inhibitor of Janus kinase (JAK)1/2, approved for treatment of moderate-to-severe- rheumatoid arthritis (RA) in adults. Here, we update the drug’s safety profile with data up to 8.4 years of treatment. Methods  Long-term safety of BARI was assessed from 9 completed randomized trials(5 Ph3, 3 Ph2, 1 Ph 1b) and 1 ongoing long-term extension(LTE) study. Incidence rates(IRs) per 100 patient-years (PY) were calculated for all RA patients treated with ≥1 dose of BARI through 1-Sep-2019(All-BARI-RA set). IRs for deep vein thrombosis(DVT), pulmonary embolism(PE), and DVT and/or PE(DVT/PE) were also calculated for groups of patients while receiving BARI 2mg/4mg within All-BARI-RA. Major adverse cardiovascular events(MACE) were adjudicated in 5 Ph3 studies and the LTE. Results  3770 pts received BARI for 13,148 PY, with median and maximum exposure: 4.2 and 8.4 years, respectively. Overall IRs per 100 PY were: for any treatment-emergent adverse event (AE)(25.8); serious AE (including death)(7.2); temporary interruption due to AE (9.5); permanent discontinuation due to AE (4.8); death (0.52); serious infection (2.7); opportunistic infection (0.46)(excluding tuberculosis [TB], including multidermatomal herpes zoster [HZ]); TB (0.15); HZ (3.0); MACE (0.50); DVT (0.31); PE (0.24); DVT/PE (0.46); malignancies excluding non-melanoma skin cancer (NMSC)(0.91); NMSC (0.33); lymphoma (0.07); and gastrointestinal perforation (0.04). (IRs)[95% confidence intervals] for patients while receiving BARI 2mg (N = 1077) and BARI 4mg (N = 3400) were DVT 2mg (0.38)[0.18, 0.73] and 4mg (0.30)[0.21, 0.43]; PE 2mg (0.26)[0.09, 0.56] and 4mg (0.25)[0.16, 0.36]; and DVT/PE 2mg (0.47)[0.23, 0.84] and 4mg (0.46)[0.34, 0.61]. IRs for death tended to increase in later time intervals (beyond 192 weeks). No particular cause of death contributed to this increase. For all other safety topics of interest, across 48-week treatment intervals, IRs remained stable over time. Across safety topics, IRs were consistent with previous analyses. Conclusion  In this update, with 3021 additional PY of exposure, BARI maintained a safety profile similar to that previously reported, with no increase of IRs across safety topics through exposures up to 8.4 years. Disclosure  K.L. Winthrop: Consultancies; AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly and Company, Pfizer, and UCB Pharma. Grants/research support; Bristol Myers Squibb and Pfizer. T. Takeuchi: Consultancies; AbbVie, Asahi Kasei Medical, Astellas, AstraZeneca, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly and Company, GlaxoSmithKline, Janssen, Mitsubishi Tanabe Pharma, Nippon Kayaku, Novartis, Pfizer Japan, Taiho Pharmaceutical, Taiho Toyama Pharmaceutical, Takeda, and UCB Japan. G. Burmester: Consultancies; Eli Lilly and Company, Janssen, Novartis, and Pfizer. Grants/research support; Eli Lilly and Company. W. Deberdt: Shareholder/stock ownership; Eli Lilly and Company. D. Schlichting: Shareholder/stock ownership; Eli Lilly and Company. D. Mo: Shareholder/stock ownership; Eli Lilly and Company. C. Walls: Shareholder/stock ownership; Eli Lilly and Company. J.S. Smolen: Consultancies; AbbVie, Amgen, AstraZeneca, Astro Pharma, Bristol Myers Squibb, Celgene, Celltrion, Chugai, Eli Lilly and Company, Gilead Sciences, ILTOO Pharma, Janssen, MedImmune, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi-Aventis, and UCB Pharma. Grants/research support; AbbVie, Eli Lilly and Company, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, and Roche.

scholarly journals The role of idecabtagene vicleucel in patients with heavily pretreated refractory multiple myeloma

2021 ◽  
Vol 12 ◽  
pp. 204062072110196
Author(s):  
Albert Oriol ◽  
Laura Abril ◽  
Anna Torrent ◽  
Gladys Ibarra ◽  
Josep-Maria Ribera
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Safety Profile ◽  
Proteasome Inhibitors ◽  
Clinical Development ◽  
Phase Iii ◽  
Acceptable Safety Profile ◽  
Refractory Multiple Myeloma ◽  
High Risk Patients ◽  
Risk Patients

The development of several treatment options over the last 2 decades has led to a notable improvement in the survival of patients with multiple myeloma. Despite these advances, the disease remains incurable for most patients. Moreover, standard combinations of alkylating agents, immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies targeting CD38 and corticoids are exhausted relatively fast in a proportion of high-risk patients. Such high-risk patients account for over 20% of cases and currently represent a major unmet medical need. The challenge of drug resistance requires the development of highly active new agents with a radically different mechanism of action. Several immunotherapeutic modalities, including antibody–drug conjugates and T-cell engagers, appear to be promising choices for patients who develop resistance to standard combinations. Chimeric antigen-receptor-modified T cells (CAR-Ts) targeting B-cell maturation antigen have demonstrated encouraging efficacy and an acceptable safety profile compared with alternative options. Multiple CAR-Ts are in early stages of clinical development, but the first phase III trials with CAR-Ts are ongoing for two of them. After the recent publication of the results of a phase II trial confirming a notable efficacy and acceptable safety profile, idecabtagene vicleucel is the first CAR-T to gain regulatory US Food and Drug Administration approval to treat refractory multiple myeloma patients who have already been exposed to antibodies against CD38, proteasome inhibitors, and immunomodulatory agents and who are refractory to the last therapy. Here, we will discuss the preclinical and clinical development of idecabtagene vicleucel and its future role in the changing treatment landscape of relapsed and refractory multiple myeloma.

Overall survival benefit from tebentafusp in patients with best response of progressive disease.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9509-9509
Author(s):  
Anthony M. Joshua ◽  
Jean-Francois Baurain ◽  
Sophie Piperno-Neumann ◽  
Paul Nathan ◽  
Jessica Cecile Hassel ◽  
...  
Keyword(s):  
Overall Survival ◽  
Safety Profile ◽  
Progressive Disease ◽  
Analysis Data ◽  
Cell Receptor ◽  
Kaplan Meier ◽  
Immortal Time Bias ◽  
Best Response ◽  
Overall Survival Benefit

9509 Background: Tebentafusp (tebe) is the first T cell receptor (TCR) therapeutic to demonstrate an overall survival (OS) benefit in a randomized Phase 3 (Ph3) study [ NCT03070392 ]. In Ph2, 42% of pts with best overall response (BOR) of progressive disease (PD) survived > 1 year (yr), suggesting RECIST-based radiographic assessments underestimate OS benefit of tebe. Here we analyzed OS in the Ph3 study in a cohort of pts with BOR of PD by comparing tebe to the control arm of investigator’s choice (IC). Methods: 378 pts were randomized in a 2:1 ratio to tebe vs. IC. BOR was assessed by investigators using RECIST v1.1. Treatment beyond first disease progression (TBP) was permitted for both arms. On the IC arm, only patients receiving pembrolizumab (pembro) continued with TBP and were included in the TBP-related analyses. No crossover to tebe was permitted; investigators were free to choose subsequent therapy. This analysis was conducted on the first interim analysis (data extracted Nov-2020). Kaplan-Meier estimates of OS were based on Day 100 landmark to eliminate immortal time bias and to capture majority of the PDs. Results: By Day 100, PD as BOR occurred in 52% (130/252) of tebe pts (PD-tebe) vs. 60% (76/126) of IC pts (PD-IC). Key baseline characteristics including lactate dehydrogenase, alkaline phosphatase, ECOG performance, age, and sex were similar between PD-tebe vs PD-IC. The proportion of pts with PD due to progression of target lesions (TL), non-TL, or new lesions were also similar between the two groups. More pts received TBP among PD-tebe 53% (69/130) vs PD-pembro 16% (10/61). Median duration of TBP was longer for PD-tebe (7 weeks) vs PD-Pembro (3 weeks). The safety profile of PD-tebe pts during TBP was similar to all tebe-treated pts. OS was superior for PD-tebe vs PD-IC, HR = 0.41 (95%CI 0.25-0.66), even when considering key baseline covariates. While some pts had regression of TL despite diagnosis of PD ( < 10% of pts), the OS benefit remained even when limited to pts with best change of tumor growth of TL, HR 0.46 (0.29, 0.73). 58% (75/130) PD-tebe and 52% (40/76) PD-IC pts received subsequent therapies. In a landmark OS analysis of these pts beginning on 1st day of subsequent therapy, prior tebe was associated with better OS vs. prior IC, HR 0.59 (95%CI 0.36-0.96). Conclusions: Tebe is the first TCR therapeutic to demonstrate an OS benefit in a solid tumor. Surprisingly, a strong OS benefit from tebe is observed even in pts with BOR of PD, suggesting that RECIST-based radiographic assessments do not capture the complete benefit from tebe. The safety profile of tebe during TBP was consistent with that for long-term tebe treatment. Clinical trial information: NCT03070392.

scholarly journals Long-term renal safety profile of ibandronate 6 mg infused over 15 minutes

Bone ◽  
2010 ◽  
Vol 46 ◽  
pp. S37-S38
Author(s):  
Roger Van Moos ◽  
Clemens Caspar ◽  
Rolf Steiner ◽  
Rahel Angst ◽  
Roman Inauen ◽  
...  
Keyword(s):  
Safety Profile ◽  
Renal Safety

scholarly journals Oral Janus Kinase Inhibitor for the Treatment of Rheumatoid Arthritis: Tofacitinib

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Han Ni ◽  
Soe Moe ◽  
Kay Thi Myint ◽  
Aung Htet
Keyword(s):  
Rheumatoid Arthritis ◽  
Safety Profile ◽  
Kinase Inhibitor ◽  
Meta Analysis ◽  
Janus Kinase ◽  
Serious Adverse Events ◽  
Janus Kinase Inhibitor ◽  
Immune Modulators ◽  
Serious Infections

Since the introduction of immune modulators in the treatment of rheumatoid arthritis (RA), there has been hope that orally effective biologic agents would be developed. Tofacitinib, a Janus kinase inhibitor, has become the first oral biologic to receive approval for use in active RA patients. This paper reviews the efficacy and safety profile of Tofacitinib at dosages of 5 mg and 10 mg twice daily. Remarkable improvement in terms of ACR 20 response and HAQ-DI score was noted at month 3 and month 6. DAS 28-4 ESR < 2.6 achievement was noticeably obvious at month 6 for both dosages. No significant serious adverse events, serious infections, neutropenia, or anaemia were observed compared to placebo. In fact, Tofacitinib 5 mg was even found to have significant protective effect of anaemia in the meta-analysis (P=0.004). Tofacitinib has a noticeable efficacy in controlling disease activity in RA with a manageable safety profile. However, longer studies are needed for its long-term safety profile.

scholarly journals Dual orexin receptor antagonist in treatment of insomnia

Engrami ◽  
2020 ◽  
Vol 42 (2) ◽  
pp. 57-68
Author(s):  
Nikola Trajanović
Keyword(s):  
Circadian Rhythm ◽  
Side Effects ◽  
Receptor Antagonist ◽  
Safety Profile ◽  
The Elderly ◽  
First Line ◽  
Future Studies ◽  
Good Safety Profile ◽  
Circadian Rhythm Disorders

A novel group of medications, dual orexin receptor antagonists, emerged as a competent group that challenges current first-line hypnotics. They have relatively infrequent and mostly well-tolerated side effects, primarily in the form of residual somnolence, fatigue and nightmares/disturbing dreams. The advantage over conventional hypnotics stems from the specifics of their target receptors, which translates into lack of tolerance after long term use and good safety profile. They are particularly favoured in some specific populations, including the elderly. Ongoing and future studies are set to explore their effect on selected conditions, such as addiction and psychiatric disorders, dementias, perimenopausal condition and circadian rhythm disorders, to name a few.

scholarly journals Long-Term Safety Profile of the Oral Spleen Tyrosine Kinase Inhibitor Fostamatinib in Immune Thrombocytopenia (ITP) and Other Diseases

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 35-36
Author(s):  
Sandra Tong ◽  
Robert P. Numerof ◽  
Jane Datangel ◽  
Esteban Masuda
Keyword(s):  
Tyrosine Kinase ◽  
Safety Profile ◽  
Safety Data ◽  
First Year ◽  
Patient Exposure ◽  
Publicly Traded ◽  
Data Set ◽  
Pooled Data ◽  
The Mean

Introduction: Fostamatinib is an oral, potent inhibitor of spleen tyrosine kinase (SYK) with proven efficacy and a manageable safety profile for the treatment of ITP. SYK is situated in an intracellular signaling pathway upstream of Bruton's tyrosine kinase (BTK). Long-term safety data on fostamatinib at various dosing regimens (up to 150 mg BID) has been collected in &gt;4000 patients with ITP, rheumatoid arthritis (RA), and other autoimmune, allergic and neoplastic disorders. The safety and tolerability of fostamatinib were consistent across different patient populations (apart from disease specific events). We present a summary analysis of the fostamatinib safety data from the ITP and RA studies. Methods: Fostamatinib safety data from 2 randomized, double-blind, placebo-controlled, phase 3 studies and the long-term, open-label, extension (OLE) study in ITP were pooled and are based on a starting dose of 200 mg/day, which was increased to 300 mg/day after 4 weeks in 88% of patients. Fostamatinib safety data from 13 phase 2/3 studies in RA were pooled and are based on a dosing regimen of 100-150 mg/day (n=1232) or 200-300 mg/day (n=2205). Results: The pooled data set for ITP included 146 patients; 60% were female, and the median age was 53 years (range 20-88). The mean duration of fostamatinib treatment was 19 months (range &lt;1-62 months), representing 229 patient exposure years. Adverse events (AEs) were reported in 87% of patients, and 63% were mild to moderate. Serious AEs were reported in 31% of patients. The incidence of diarrhea, hypertension, alanine aminotransferase increase (ALT), and aspartate aminotransferase (AST) increase was evaluated in 58 patients who received fostamatinib for ≥1 year. This enabled a comparison of the incidence of these AEs in quartiles over the first year to assess the cumulative effects of fostamatinib. The AEs were reported with decreasing frequency during the second, third, and fourth quarters of fostamatinib treatment compared with the first quarter of the initial year of treatment in the 58 patients (see Figure 1). In the same 58 patients, the use of rescue therapy decreased while median platelet counts increased each quarter of the first year. The pooled data set for RA included 3437 patients who received fostamatinib; 83% were female, and the median age was 54 (range 18 -87). The mean duration of treatment was 18 months (range &lt;1-81) representing 5134 patient exposure years. AEs were reported in 86% of RA patients and were mild to moderate in 73% of RA patients. Serious AEs occurred in 14%. In the placebo-controlled RA studies, 2414 patients received fostamatinib with 823 patient exposure years and 1169 received placebo with 367 patient exposure years. Despite a two-fold (125%) increase in exposure with fostamatinib vs placebo (823 vs 367 patient exposure years), there was only a 26% increase in AEs with fostamatinib vs placebo (68% vs 54%). The most common events in the ITP and RA studies were diarrhea (36% and 24%), hypertension (22% and 19%) and nausea (19% and 8%), apart from disease-related AEs. Epistaxis (19% and 0.5%), petechiae (15% and 0.3%), contusion (12% and 2%), and fatigue (10% and 2%) are associated with ITP and were uncommon in the RA population. Rheumatoid arthritis was reported as an AE in 9% of patients with RA and in none with ITP. Some AEs may be dose-related, and one-third of the RA patients were on lower dosages (100-150 mg/day) than were generally given in the ITP trials (200-300 mg/day). Conclusions: Fostamatinib has been evaluated in &gt;4000 patients across different disease populations. Fostamatinib has a consistent and manageable safety profile. No new safety signals and no cumulative toxicity were observed with up to 81 months (6.8 years) of continuous treatment. Figure 1 Disclosures Tong: Rigel: Current Employment, Current equity holder in publicly-traded company. Numerof:Rigel: Current Employment, Current equity holder in publicly-traded company. Datangel:Rigel: Current Employment, Current equity holder in publicly-traded company. Masuda:Rigel: Current Employment, Current equity holder in publicly-traded company.

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