The lipid-lowering effects of lomitapide are unaffected by adjunctive apheresis in patients with homozygous familial hypercholesterolaemia - a post-hoc analysis of a Phase 3, single-arm, open-label trial.

OBJECTIVE: Lomitapide (a microsomal triglyceride transfer protein inhibitor) is an adjunctive treatment for homozygous familial hypercholesterolaemia (HoFH), a rare genetic condition characterised by elevated low-density lipoprotein-cholesterol (LDL-C), and premature, severe, accelerated atherosclerosis. Standard of care for HoFH includes lipid-lowering drugs and lipoprotein apheresis. We conducted a post-hoc analysis using data from a Phase 3 study to assess whether concomitant apheresis affected the lipid-lowering efficacy of lomitapide. METHODS: Existing lipid-lowering therapy, including apheresis, was to remain stable from Week -6 to Week 26. Lomitapide dose was escalated on the basis of individual safety/tolerability from 5 mg to 60 mg a day (maximum). The primary endpoint was mean percent change in LDL-C from baseline to Week 26 (efficacy phase), after which patients remained on lomitapide through Week 78 for safety assessment and further evaluation of efficacy. During this latter period, apheresis could be adjusted. We analysed the impact of apheresis on LDL-C reductions in patients receiving lomitapide. RESULTS: Of the 29 patients that entered the efficacy phase, 18 (62%) were receiving apheresis at baseline. Twenty-three patients (13 receiving apheresis) completed the Week 26 evaluation. Of the six patients who discontinued in the first 26 weeks, five were receiving apheresis. There were no significant differences in percent change from baseline of LDL-C at Week 26 in patients treated (-48%) and not treated (-55%) with apheresis (p = 0.545). Changes in Lp(a) levels were modest and not different between groups (p = 0.436). CONCLUSION: The LDL-C lowering efficacy of lomitapide is unaffected by lipoprotein apheresis.

Bone density and depression in premenopausal South African women: a pilot study.

OBJECTIVE: It is posited that the effect of depression on BMD is dependent on the severity of depression. Conflicting evidence exists regarding this possible association. This study investigated the association between depression and low bone mineral density (BMD). METHODS: The hypothesis was investigated in a random sample of volunteers (n=40) and in premenopausal female psychiatric patients (n=5) diagnosed with recurrent severe major depression. The outcome measures were BMD (DEXA); depression (Beck Depression Inventory and Psychological General Well-being Scale) and 24-hour saliva cortisol levels (ELISA). In a comparison of women (4 of the 40 i.e. "control" subjects) with negligible symptoms of depression and the five patients with severe recurrent major depression- BMD, depression, saliva cortisol and bone turnover markers were measured and compared. Pro-inflammatory status (IL-1 and TNF-alpha) was investigated in the psychiatric patients only. RESULTS: In the random - non clinical - sample of women (n=40), 26 exhibited normal BDM and 14 exhibited low BMD. Drepressive symptoms and cortisol level were not significantly different between these two groups. Women with severe recurrent major depression (n=5)exhibited lower median BMD T-scores, higher overall bone turnover and higher 24-hour cortisol levels compared to "control" subjects (n=4). The psychiatric patients also exhibited elevated IL-1 levels. CONCLUSION: The effect of depression on BMD may be dependent on the depression severity, IL-1 and cortisol are possible mediators in depression-induced BMD loss.