Erenumab for Migraine Prevention in a 1-Year Compassionate Use Program: Efficacy, Tolerability, and Differences Between Clinical Phenotypes.

During a 1-year compassionate use program, 156 patients with migraine self-administered a monthly dose of erenumab 140 mg with a subcutaneous autoinjector. Main inclusion criteria were: ≥ 4 migraine days/month and ≥two prior prophylactic treatment failures. The patients covered the migraine severity spectrum from episodic migraine (EM) (n = 80) to chronic migraine (CM) (n = 76). During the 3rd month of treatment, monthly headache days decreased by 45.7% in EM and 35.5% in CM. The 50% responder rate for reduction in monthly headache days was significantly higher in EM (55%) than in CM (43%) (p = 0.05). In both the migraine subgroups, the clinical improvement vs. baseline was already significant during the 1st month of treatment (p < 0.001). There were also significant reductions in mean headache severity, duration, and monthly days with acute drug intake. The 30% responder rate at 3 months was 60% in CM and 54.1% of patients reversed from CM to EM. The therapeutic effect was maintained at 12 months when 50% responder rates, considering discontinuation for lack of efficacy or adverse effects as 0% response, still were 51% in EM and 41% in CM. A total of 10 patients with EM (12.5%) and 23 patients with CM (30.3%) had discontinued treatment, considering the treatment as ineffective. At 3 months, 48% of patients reported non-serious adverse events among which the most frequent was constipation (20.5%); corresponding figures at 12 months were 30 and 15%. Discontinuation due to an adverse effect for the entire 12 month period was rare (3.8%). The lower efficacy in CM than in EM was mainly due to a very low 50% responder rate in patients with CM with continuous pain (13%) as compared to CM with pain-free periods (58%) (p < 0.001). Similarly, the 50% responder rate was lower in patients with ≥two prior prophylactic treatment failures (40.5%) compared to those with two failures (70%) (p < 0.05). There was no significant efficacy difference between low (4-7 migraine days/month, n = 22) and high frequency (8-14 days, n = 59) EM nor between patients with CM with (n = 50) or without (n = 26) acute medication overuse. Erenumab had no effect on the frequency of auras. Taken together, erenumab 140 mg monthly was highly effective for migraine prophylaxis over the whole severity spectrum of the disease, except in patients with continuous headaches. Its effect is significant after the first injection, quasi-maximal after the second injection, and does not wear off after 12 months. The most frequent adverse effect was constipation. These results are compared to those published for erenumab in the pivotal randomized placebo-controlled trials and to those reported in several recent real-world studies.

Monocyte Chemotactic Protein-1-Interleukin-6-Osteopontin Pathway of Intra-Aneurysmal Tissue Healing.

BACKGROUND AND PURPOSE: We have previously demonstrated that the local delivery of monocyte chemotactic protein-1 (MCP-1) via an MCP-1-releasing poly(lactic-co-glycolic acid)-coated coil promotes intra-aneurysmal tissue healing. In this study, we demonstrate that interleukin-6 (IL-6) and osteopontin are downstream mediators in the MCP-1-mediated aneurysm-healing pathway. METHODS: Murine carotid aneurysms were created in C57BL/6 mice. Drug-releasing coils (MCP-1, IL-6, and osteopontin) and control poly(lactic-co-glycolic acid) coils were created and then implanted into the aneurysms to evaluate their intra-aneurismal-healing capacity. To investigate the downstream mediators for aneurysm healing, blocking antibodies for IL-6 receptor and osteopontin were given to the mice implanted with the MCP-1-releasing coils. A histological analysis of both murine and human aneurysms was utilized to cross-validate the data. RESULTS: We observed increased expression of IL-6 in MCP-1-coil-treated aneurysms and not in control-poly(lactic-co-glycolic acid)-only-treated aneurysms. MCP-1-mediated intra-aneurysmal healing is inhibited in mice given blocking antibody to IL-6 receptor. MCP-1-mediated intra-aneurysmal healing is also inhibited by blocking antibody to osteopontin. The role of IL-6 in intra-aneurysmal healing is in recruiting of endothelial cells and fibroblasts. Local delivery of osteopontin to murine carotid aneurysms via osteopontin-releasing coil significantly promotes intra-aneurysmal healing, but IL-6-releasing coil does not, suggesting that IL-6 cannot promote aneurysm healing independent of MCP-1. In the MCP-1-mediated aneurysm healing, osteopontin expression is dependent on IL-6; inhibition of IL-6 receptor significantly inhibits osteopontin expression in MCP-1-mediated aneurysm healing. CONCLUSIONS: Our findings suggest that IL-6 and osteopontin are key downstream mediators of MCP-1-mediated intra-aneurysmal healing.

Clinical effect of active immunotherapy combined with endometrial local injury treatment in women with recurrent spontaneous abortion / 中国基层医药

Objective To investigate the clinical effect of active immunotherapy combined with endometrial local injury in women with recurrent spontaneous abortion( RSA) caused by negative-blocking antibodies.Methods 112 patients diagnosed RSA with negative -blocking antibodies were randomly divided into the treatment group (62 patients) and control group (50 patients).The patients in treatment group were treated by active immunotherapy combined with endometrial local injury.The patients in the control group were treated by active immunotherapy.The pregnancy outcomes were observed.Results The rate of pregnancy was 93.54%in treatment group,and 80.00%in the control group.The success pregnancy rate in the treatment group was significant higher than that in the control group (χ2 =4.65,P<0.05).The rate of abortion was 3.44% in the treatment group and 12.50% in the control group.It was significant lower than the control group(χ2 =4.90,P<0.05).After active immunotherapy,the pregnan-cy rate was 90.58%in positive-blocking antibodies group and 77.77%in negative-blocking antibodies group.The success pregnancy rate in positive-blocking antibodies group was significant higher than that in negative-blocking antibodies group (χ2 =4.27,P<0.05).The abortion rate in positive-blocking antibodies group was 2.60% and 19.05%in negative-blocking antibodies group.It was significant lower than that in negative-blocking antibodies group (χ2 =6.14,P<0.05).Conclusion It can significantly improve pregnant outcome and reduce the abortion rate with active immunotherapy combined with endometrial local injury in women with recurrent spontaneous abortion ( RSA) caused by negative-blocking antibodies.

Influence of the blocking antibodies on paternal T lymphocyte differentiation antigens (CD3,CD4 and CD8) in women with pregnancy induced hypertension / 中华围产医学杂志

Objective To study the association between paternal CD3, CD4 and CD8 antigenecity to their pregnant spouses and the development of pregnancy induced hypertension (PIH). Methods Maternal serum from 15 women with PIH in the third trimester and 82 in normal pregnancies (16 in the first, 32 in the second and 34 in the third trimester) were incubated with paternal T lymphocytes. Monoclonal CD3, CD4 and CD8 fluorescent conjugated antibodies were then added and the percentage of paternal T cell differentiation antigen CD3, CD4 and CD8 were measured by flow cytometry. Results During normal pregnancy, the levels of maternal serum blocking antibodies on paternal CD3, CD4 and CD8 were (4.14?1.02, 2.02 ?0.24, 2.37?1.05)% in first trimester, (-0.29?0.13, 1.03?0.27, 0.65?0.23)% in the second trimester and (-1.33?1.47,0.15?0.01, -1.04? 0.37)% in the third trimester. There were significant difference between them( P