Efficacy and safety of switching to pasireotide LAR monotherapy or in combination with pegvisomant in acromegaly patients controlled with combination therapy of somatostatin analogues and pegvisomant (PAPE study): a prospective, open-label 48 week study

2018 ◽  
Author(s):  
Eva C Coopmans ◽  
Ammar Muhammad ◽  
Joseph AMJL Janssen ◽  
der Lely Aart J van ◽  
Sebastian JCMM Neggers
Keyword(s):  
Combination Therapy ◽  
Somatostatin Analogues ◽  
Efficacy And Safety ◽  
Open Label

scholarly journals Open randomized study of cefepime versus piperacillin-gentamicin for treatment of febrile neutropenic cancer patients.

1997 ◽  
Vol 41 (8) ◽  
pp. 1704-1708 ◽  
Author(s):  
D Yamamura ◽  
R Gucalp ◽  
P Carlisle ◽  
M Cimino ◽  
J Roberts ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Cancer Patients ◽  
Randomized Study ◽  
Response Rates ◽  
Efficacy And Safety ◽  
Open Label ◽  
Gram Negative ◽  
Underlying Malignancy ◽  
Neutropenic Patients ◽  
Febrile Episodes

An open-label randomized trial comparing the efficacy and safety of cefepime versus piperacillin plus gentamicin (P+G) given intravenously for the treatment of febrile episodes in neutropenic patients with underlying malignancy was conducted at two oncology centers. Over a 30-month period 111 patients were enrolled and 99 patients were found to be suitable for evaluation. At the 72-h time of evaluation, cefepime monotherapy and P+G combination therapy produced comparable clinical response rates (78% for both). P+G and cefepime produced comparable response rates in microbiologically documented (78 versus 71%), clinically documented (100 versus 100%), and possible (75 versus 79%) infections. The P+G and cefepime treatments achieved comparable microbiological eradication of gram-negative (100 versus 71%) (P = 0.09) and gram-positive (44 versus 70%) (P = 0.37) organisms. There were no statistically significant differences in the rates of superinfection between the groups; however, more superinfections of fungal origin were noted in the P+G group. Cefepime was demonstrated to be an effective and safe treatment for febrile episodes in neutropenic patients with malignancies, and its lack of nephrotoxicity compared to P+G was noteworthy. Cefepime appears to be a candidate for monotherapy in febrile neutropenic cancer patients.

scholarly journals Tamibarotene Compared to All-Trans Retinoic Acid (ATRA) As Add-on to Arsenic Trioxide (ATO) in Subjects with Relapsed Acute Promyelocytic Leukemia (APL)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 220-220 ◽  
Author(s):  
Jianxiang Wang ◽  
Yingchang Mi ◽  
Bin Jiang ◽  
Xiequn Chen ◽  
Chunyan Ji ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Combination Therapy ◽  
Phase Iii ◽  
Control Group ◽  
Study Group ◽  
Efficacy And Safety ◽  
Intergroup Difference ◽  
Open Label ◽  
Serious Adverse Events ◽  
Retinoic Acid Syndrome

Abstract Background Combination therapy with ATRA and ATO is a standard therapy for relapsed APL. Despite the high complete remission (CR) rate with ATRA-ATO combination therapy, patients administered this combination for relapsed disease may acquire tolerance to ATRA, which reduces the CR rate in relapsed APL patients. Tamibarotene is a novel synthetic retinoid created in Japan with a several-fold-higher differentiation-inducing effect than ATRA, as well as low affinity for cellular retinoic acid-binding protein and absence of binding affinity for RARγ, unlike ATRA. It has been used for treating patients relapsed after ATRA therapy since 2005 in Japan. We conducted a phase III, randomized, open-label, parallel-group, active-controlled, multicenter clinical trial to compare tamibarotene-ATO and ATRA-ATO combination therapies in relapsed APL patients. Methods A Phase III, randomized, open-label, parallel-group, active-controlled, multicenter, study of 56 days treatment duration will evaluate the efficacy and safety of 6mg/m2/day Tamibarotene versus 25mg/m2/day ATRA as add-on to 0.15mg/kg/day ATO in subjects with relapsed APL. 71 subjects were randomly assigned to 1 of 2 treatment groups: ATRA-ATO (control group) or tamibarotene-ATO (study group). Results The number of subjects for efficacy analysis constituting a full analysis set (FAS) of all subjects administered study drugs, including drop-outs, was 35 each in the control and study groups. The number of subjects in each per protocol set (PPS), excluding drop-outs, was 27 and 33 in the control and study groups, respectively. CR rate for the FAS was significantly higher in the study group (80.00% vs. 54.29%; P = 0.0220, Table 1). In contrast, CR rate for the PPS was 84.85% and 70.37% for the study and control groups, respectively. The intergroup difference was 14.48% with a 97.1% confidence interval of -9.06 to 38.01%, which fulfilled requirements for non-inferiority of Δ = 0.10. These results verified the non-inferiority of the study to the control group. Of the patients who attained CR, the number who showed complete molecular remission (CRm) was higher in the study group, suggesting that a higher quality of remission was possibly attained in the study group (Table 2). Serious adverse events occurred in 3 control group patients (intracerebral hemorrhage, 2 and retinoic acid syndrome, 1) and 1 patient in the study group (type I respiratory failure). There was no significant intergroup difference in the incidences of serious adverse events. The most commonly reported adverse reactions included hypertriglyceridemia, hypercholesterolemia, rash, and elevation of ALT and AST levels; there was no significant intergroup difference in the incidences of any of these adverse reactions. Other adverse reaction findings were similar between the groups. Therefore, the tolerability observed in the study group was considered to be similar to that in the control. The only adverse finding that showed an appreciable intergroup difference was leukocytosis, which occurred at a significantly lower frequency in the study group than in the control group. Therefore, the therapeutic regimen of the study group might reduce the risk of retinoic acid syndrome, an important adverse reaction in treatment of APL, when the association of leukocytosis with development of retinoic acid syndrome is considered. Conclusion This controlled clinical trial demonstrated the efficacy and safety of combination therapy with tamibarotene and ATO in patients with relapsed APL. Tamibarotene-ATO combination therapy was considered not inferior in efficacy and safety to the standard combination of ATRA and ATO, and may be a useful new combination regimen for treating relapsed APL. Disclosures No relevant conflicts of interest to declare.

O-132 Sustained efficacy and safety of relugolix combination therapy in women with endometriosis-associated pain: SPIRIT 52-week data

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
S As-Sanie ◽  
L Giudice ◽  
M S Abrao ◽  
K Wilk ◽  
C Mehedintu ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Efficacy And Safety ◽  
Mineral Density ◽  
Open Label ◽  
Substantial Impact ◽  
Once Daily ◽  
Sustained Improvement ◽  
Pain Domain ◽  
Extension Period

Abstract Study question To assess the long-term (52-week) efficacy and safety of relugolix combination therapy (Relugolix-CT) in the treatment of endometriosis-associated pain. Summary answer Relugolix-CT demonstrated a sustained improvement of endometriosis-associated pain and maintenance of bone mineral density (BMD) over the extension treatment period. It was well tolerated. What is known already Endometriosis is a chronic condition characterized by symptoms of menstrual and non-menstrual pain, and dyspareunia, which have a substantial impact on women’s lives. SPIRIT 1 and 2 were Phase 3, randomized, double-blind, placebo-controlled studies of once-daily Relugolix-CT (relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg) in premenopausal women (age 18–50 years) with surgically diagnosed endometriosis and moderate-to-severe dysmenorrhea and non-menstrual pelvic pain (NMPP) at baseline. These trials demonstrated a significant improvement of dysmenorrhea, NMPP and dyspareunia in women treated with Relugolix-CT, with a minimal decline in BMD vs placebo over 24 weeks. Study design, size, duration Women who completed the 24-week pivotal studies (SPIRIT 1 and 2 trials) were eligible to enroll in an open-label, single-arm, long-term safety and efficacy extension study for an additional 80 weeks. All women received once-daily oral Relugolix-CT. Analyses were done based on original randomization in pivotal studies: Relugolix-CT, delayed Relugolix-CT (relugolix 40 mg alone for 12 weeks, then Relugolix-CT for 12 weeks), or placebo. Here, 52-week efficacy and safety outcomes are presented. Participants/materials, setting, methods The primary endpoints were the proportion of dysmenorrhea and NMPP responders at Week 52, based on daily Numerical Rating Scale (NRS) scores (0=no pain, 10=worst pain imaginable). A responder was a woman who achieved a predefined, clinically meaningful reduction from baseline in NRS score with no increase in analgesic use. Secondary efficacy endpoints included change in Endometriosis Health Profile-30 (EHP-30) pain domain scores, and analgesic/opioid use. Safety endpoints included adverse events (AEs) and BMD evaluation. Main results and the role of chance Of 1261 randomized patients, 1044 completed the primary studies; 802 enrolled in the long-term extension and 681 completed 52 weeks of treatment. Baseline demographics and clinical characteristics of the extension population were consistent with those of the original randomized population. Sustained improvement of endometriosis-associated pain was demonstrated with Relugolix-CT through 52 weeks, the proportion of responders for dysmenorrhea was 84.8% and 73.3% for NMPP. NRS least squares (LS) mean scores for dysmenorrhea and NMPP decreased from 7.4 (severe) and 6.0 (moderate) at SPIRIT study baseline to 1.3 (mild) and 2.2 (mild) at Week 52, equating to 82.8% and 62.9% reduction in dysmenorrhea and NMPP, respectively. Mean NRS for dyspareunia decreased from 5.9 (moderate) to 2.4 (mild), demonstrating 60.1% reduction with Relugolix-CT. Daily functioning measured by the EHP-30 pain domain score was improved (–38.1 point) and the majority of women (85.6%) were opioid-free at Week 52. There was no disproportionate increase in the incidence of AEs in the Relugolix-CT group with no new safety signals identified through the 52 weeks. BMD was preserved over the extension period with overall LS mean change from baseline to Week 52 of –0.83% (95% CI: –1.34, –0.32) for lumbar spine in the Relugolix-CT group. Limitations, reasons for caution The study was conducted as an open-label study without a control group over the 28 weeks of the extension period. Wider implications of the findings Relugolix-CT demonstrated a sustained improvement of dysmenorrhea, NMPP, and dyspareunia, and reduced pain-related functional limitations and the need for opioids over 52 weeks in women with moderate-to-severe endometriosis-associated pain. Relugolix-CT was generally well tolerated and associated with minimal BMD loss after treatment initiation followed by BMD maintenance over 52 weeks. Trial registration number NCT03654274

AB0301 SARILUMAB AS MONOTHERAPY OR IN COMBINATION WITH CONVENTIONAL SYNTHETIC DMARDS IN PATIENTS WITH RHEUMATOID ARTHRITIS: 12-WEEK TREATMENT RESULTS FROM A MULTICENTER, OPEN-LABEL, PROSPECTIVE, SINGLE-ARM OBSERVATIONAL STUDY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1450.1-1450
Author(s):  
A. Kivitz ◽  
J. E. Gottenberg ◽  
M. Bergman ◽  
M. Iglesias-Rodriguez ◽  
G. St John ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Practice ◽  
Combination Therapy ◽  
Observational Study ◽  
Interim Analysis ◽  
Routine Clinical Practice ◽  
Efficacy And Safety ◽  
Research Support ◽  
Open Label ◽  
Synthetic Dmards

Background:Due to strict inclusion/exclusion criteria, randomized controlled trials (RCTs) may not represent the heterogeneous rheumatoid arthritis (RA) population encountered in routine clinical practice; longitudinal observational studies are needed to complement learnings from RCTs. The PROspective sarilumab (preFILled syringe/pen) multinational, obsErvational Study (PROFILE) is collecting information on treatment strategies and sarilumab usage patterns and adherence in routine clinical practice for up to 52 weeks in patients with moderate-to-severe RA.Objectives:In this planned interim analysis, we report baseline characteristics of patients prescribed sarilumab in routine clinical practice and the efficacy and safety of sarilumab after 12 weeks of treatment.Methods:Adults with RA (2010 ACR/EULAR criteria) can enroll in this multinational, open-label, single-arm, Phase 4 study if, per their treating physicians’ judgment, they are to initiate treatment with sarilumab as mono- or combination (with csDMARD) therapy, in accordance with local labeling/prescribing information, ≤4 weeks prior to or ≤8 weeks after study Visit 1 (signed informed consent and disease characteristics documented); 1000 patients are planned for enrollment. Concomitant use of biologic or targeted synthetic DMARDs (b/tsDMARDs) is not permitted. Primary endpoint is change from baseline in Clinical Disease Activity Index (CDAI) score at Weeks 24 and 52. Statistical analyses are descriptive.Results:This analysis included 291 patients who reached, or discontinued before, the Week 12 visit, of whom 108 (37%) received sarilumab mono- and 183 (63%) received combination therapy. At baseline (BL), the monotherapy group had longer disease duration and a smaller proportion of b/tsDMARD-naïve patients than the combination therapy group (9.7 vs 8.7 years and 39% vs 53%). Baseline and week 12 CDAI values were available in 132 patients. Mean (SD) BL CDAI scores for the monotherapy and combination groups were 26.7 (13.1) and 27.0 (14.4). At Week 12, CDAI scores were improved by −9.1 (17.5) and −10.5 (13.9), and 37% (19/51) of patients receiving monotherapy and 48% (45/93) of those receiving combination therapy had achieved low disease activity (CDAI ≤10). Remission (CDAI ≤2.8) was achieved by 12% (6/51) of monotherapy and 20% (19/93) of combination-therapy patients. Overall, 55 (19%) discontinued sarilumab: 27 (9%) for an adverse event (AE), 19 (7%) for insufficient response, 4 (1%) for noncompliance, 5 (2%) for other reasons. Severe AEs leading to treatment discontinuation were leukopenia and neutropenia (n=1 patient), peripheral swelling (1), lung cancer (1), and fatigue (1). Ten patients (3%) had a treatment-emergent serious AE.Conclusion:In this planned interim analysis, sarilumab mono- or combination therapy resulted in improved disease outcomes, assessed by CDAI, at Week 12, an important treat-to-target time point. Safety and efficacy were consistent with Phase 3 trial findings, with no new safety signals, although interim results must be interpreted with caution. Future analyses will evaluate efficacy and safety after 24 and 52 weeks of treatment in routine clinical practice.Acknowledgments:Study funding and medical writing support (Laura George, Adelphi Communications Ltd, Macclesfield, UK) were provided by Sanofi Genzyme (Cambridge, USA) and Regeneron Pharmaceuticals, Inc. (Tarrytown, USA) in accordance with Good Publication Practice (GPP3) guidelines.Disclosure of Interests:Alan Kivitz Shareholder of: AbbVie, Amgen, Gilead, GSK, Pfizer Inc, Sanofi, Consultant of: AbbVie, Boehringer Ingelheim,,Flexion, Genzyme, Gilead, Janssen, Novartis, Pfizer Inc, Regeneron, Sanofi, SUN Pharma Advanced Research, UCB, Paid instructor for: Celgene, Genzyme, Horizon, Merck, Novartis, Pfizer, Regeneron, Sanofi, Speakers bureau: AbbVie, Celgene, Flexion, Genzyme, Horizon, Merck, Novartis, Pfizer Inc, Regeneron, Sanofi, Jacques-Eric Gottenberg Grant/research support from: Bristol-Myers Squibb, Pfizer, Roche, Consultant of: AbbVie, Bristol-Myers Squibb, Janssen, Lilly, MSD, Pfizer, Roche, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Lilly, MSD, Pfizer, Roche, UCB, Martin Bergman Shareholder of: Johnson & Johnson – stockholder, Consultant of: AbbVie, BMS, Celgene Corporation, Genentech, Janssen, Merck, Novartis, Pfizer, Sanofi – consultant, Speakers bureau: AbbVie, Celgene Corporation, Novartis, Pfizer, Sanofi – speakers bureau, Melitza Iglesias-Rodriguez Shareholder of: Sanofi Genzyme, Employee of: Sanofi Genzyme, Gregory St John Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., Chunfu Qiu Shareholder of: Sanofi Genzyme, Employee of: Sanofi Genzyme, Hubert van Hoogstraten Shareholder of: Sanofi, Employee of: Sanofi, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi

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