Novel strategies for improving hematopoietic reconstruction after allogeneic hematopoietic stem cell transplantation or intensive chemotherapy.
Baron, Frédéric ;
in Expert Opinion on Biological Therapy (2017)
INTRODUCTION: High-dose conditioning regimens for allogeneic hematopoietic cell transplantation (allo-HCT) as well as intensive poly-chemotherapy for acute myeloid leukemia (AML) induce prolonged periods ... [more ▼]
INTRODUCTION: High-dose conditioning regimens for allogeneic hematopoietic cell transplantation (allo-HCT) as well as intensive poly-chemotherapy for acute myeloid leukemia (AML) induce prolonged periods of neutropenia. The duration of the neutropenia is particularly long following umbilical cord blood transplantation (UCBT). Areas covered: After briefly reviewing the impact of hematopoietic growth factors administration to hasten hematologic reconstitution after allo-HCT or intensive AML chemotherapy, this article summarizes recent approaches that have been investigated to prompt hematologic reconstruction after UCBT or intensive AML chemotherapy. Expert opinion: In the allo-HCT setting, administration of G-CSF or GM-CSF shortened the duration of the neutropenia but failed to decrease infection-related mortality or to improve survival. Novel approaches to hasten hematological reconstruction after UCBT such as double UCBT with expansion of one of the 2 UCB units with Notch ligand, mesenchymal stromal cells, nicotinamide, or StemRegenin 1, co-transplanting a single UCB unit with HLA-haploidentical CD34+ cells, or increasing UCB HSC homing to marrow niches via direct intra bone UCB administration, pulse treatment with dmPGE2 or enforced fucosylation are promising and deserve further investigations in prospective phase III studies. In the AML setting, G-CSF or GM-CSF administration after intensive chemotherapy decreased the duration of the neutropenia without improving survival. [less ▲]Detailed reference viewed: 15 (3 ULg)
Dulaglutide for the treatment of type 2 diabetes.
in Expert Opinion on Biological Therapy (2017), 17(4), 485-496
INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are injectable agents used for the treatment of hyperglycemia in type 2 diabetes. The interest for this pharmacological class is rising ... [more ▼]
INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are injectable agents used for the treatment of hyperglycemia in type 2 diabetes. The interest for this pharmacological class is rising with the development of once weekly compounds and the demonstration of a potential reduction in cardiorenal outcomes. Areas covered: The paper describes the main pharmacokinetic/pharmacodynamic characteristics of dulaglutide, a new once-weekly GLP-1 RA. Dulaglutide was extensively investigated in the phase-3 AWARD program, which demonstrated its safety and efficacy when compared to placebo or active glucose-lowering agents in patients treated with diet alone, metformin or sulfonylurea monotherapy, oral dual therapies and basal insulin. In both Caucasian and Japanese patients, comparative trials showed better glucose control with dulaglutide, with a minimal risk of hypoglycemia and weight loss, but at the expense of an increased dropout rate due to side effects, mostly transient gastrointestinal disturbances. Dulaglutide proved its non-inferiority versus liraglutide and the safety and tolerance profile is similar to that of other GLP-1 RAs. Expert opinion: The once-weekly formulation and the combined positive effects on both glucose control and weight improves patient satisfaction despite nausea. Dulaglutide must prove its capacity to reduce cardiovascular and diabetic complications in the ongoing prospective REWIND trial. [less ▲]Detailed reference viewed: 17 (1 ULg)
Focus on skin cancer association and progression under TNF antagonist therapy.
PIERARD-FRANCHIMONT, Claudine ; PIERARD, Gérald ; QUATRESOOZ, Pascale
in Expert Opinion on Biological Therapy (2011), 11(9), 1215-22
INTRODUCTION: Basal and squamous cell carcinomas are the most common non-melanoma skin cancers (NMSC) in humans. Their prevalence is higher in immunocompromized patients. Results of some animal ... [more ▼]
INTRODUCTION: Basal and squamous cell carcinomas are the most common non-melanoma skin cancers (NMSC) in humans. Their prevalence is higher in immunocompromized patients. Results of some animal experiments have indicated that TNF acts both as a tumour promotor and an inductor of apoptosis. AREAS COVERED: Peer-reviewed articles about human skin cancers possibly related to TNF antagonists. The occurrence and growth kinetics of NMSC are possibly increased in some patients under TNF antagonist therapy. Other issues of such biological treatment suggested include the activation of other distinct skin malignancies, including malignant melanoma. Benign melanocytic tumours appear to be boosted as well. At present, most of the reported findings only represent anecdotal case reports. The influence of cumulative co-factors must not be neglected, particularly the effect of other therapies administered to the patients. The occurrence of antibodies to some TNF antagonists may decrease both the treatment efficacy and the risk of skin cancer progression. EXPERT OPINION: More research needs to be performed in order to firmly establish and understand the risk of anti-TNF biologicals in the area of human skin cancers. At present, NMSC progression appears to be boosted on areas of skin field cancerization. Benign melanocytic naevi may develop as well. [less ▲]Detailed reference viewed: 65 (2 ULg)
The therapeutic potential of TNF-alpha antagonists for skin psoriasis comorbidities.
Pierard, Gérald ; Pierard, Claudine ; Szepetiuk, Grégory et al
in Expert Opinion on Biological Therapy (2010), 10(8), 1197-208
IMPORTANCE OF THE FIELD: Alopecia, psoriatic arthritis, the metabolic syndrome, inflammatory bowel diseases and cardiovascular diseases may occur as skin psoriatic comorbidities. TNF-alpha antagonists are ... [more ▼]
IMPORTANCE OF THE FIELD: Alopecia, psoriatic arthritis, the metabolic syndrome, inflammatory bowel diseases and cardiovascular diseases may occur as skin psoriatic comorbidities. TNF-alpha antagonists are used to treat psoriasis. Adalimumab is one of the recognized active agents for this indication. AREAS COVERED IN THIS REVIEW: The current peer-reviewed publications and presentation of original findings. WHAT THE READER WILL GAIN: Adalimumab is active on recalcitrant psoriasis and some of its comorbidities, particularly arthropathies and Crohn's disease. However, the progression of the radiological alterations is limited with regression of the bony erosions. Psoriatic enthesopathy also regresses. Mortality associated with psoriasis arthropathy is on the decline. Crohn's disease, the most frequent inflammatory bowel comorbidity of psoriasis, is responsive to adalimumab. The effect of adalimumab on the metabolic syndrome and cardiovascular involvement is more erratic. The spectacular effects of adalimumab may be associated with some adverse effects. In particular, despite a marked reduction in the psoriasis area-and-severity index (PASI) score some new acute lesions of cutaneous psoriasis may develop corresponding to paradoxical psoriasis. Other potential adverse effects include infections, granulomas, rapid growth of cancers and occurrence of lymphomas. TAKE HOME MESSAGE: Adalimumab frequently controls moderate-to-severe forms of cutaneous psoriasis and some of its comorbidities. [less ▲]Detailed reference viewed: 48 (5 ULg)