Comparative effectiveness of erenumab versus rimegepant for migraine prevention using matching-adjusted indirect comparison.

Aim: To compare the efficacy of erenumab versus rimegepant as preventive treatment for patients with episodic and chronic migraine using an anchor-based matching-adjusted indirect comparison. Methods: Patients from two phase II/III trials for erenumab (NCT02066415 and NCT02456740) were pooled and weighted to match on the baseline effect modifiers (age, sex, race, baseline monthly migraine days [MMDs], and history of chronic migraine [CM]) reported in the phase II/III trial for rimegepant (NCT03732638). Four efficacy outcomes were compared between the two erenumab regimens (70 mg and 140 mg) and rimegepant, including changes in MMDs from baseline to month 1 and month 3, changes in Migraine-Specific Quality of Life Questionnaire role function - restrictive domain score from baseline to month 3, and change in disability from baseline to Month 3. Results: Compared with rimegepant, erenumab 70 mg was associated with a statistically significant reduction in MMDs at month 3 (-0.90 [-1.76, -0.03]; p = 0.042) and erenumab 140 mg was associated with statistically significant reductions in MMDs at month 1 (-0.94 [-1.70, -0.19]; p = 0.014) and month 3 (-1.28 [-2.17, -0.40]; p = 0.005). The erenumab regimens also had numerical advantages over rimegepant for other efficacy outcomes. Conclusion: In the present study, we found that erenumab had a more favorable efficacy profile than rimegepant in reducing MMDs at month 1 and month 3 for migraine prevention. These results may help with decision-making in clinical practice and can be further validated in future clinical trials or real-world studies.

Assessment of the relative effectiveness of erenumab compared with onabotulinumtoxinA for the prevention of chronic migraine.

OBJECTIVE: To assess the available clinical and economic evidence of erenumab vs onabotulinumtoxinA for chronic migraine (CM) and present de-novo indirect treatment comparisons (ITCs) based on available clinical trial data. METHODS: We conducted ITCs based on results from the pivotal 295 trial (NCT02066415) of erenumab vs placebo and published aggregate data from the PREEMPT 1 (NCT00156910) and PREEMPT 2 (NCT00168428) trials of onabotulinumtoxinA vs placebo. ITCs were conducted for CM patients with and without prior administration of onabotulinumtoxinA and among CM patients with ≥3 prior preventive treatment failures. Efficacy was assessed based on responder rates of ≥50% reductions in monthly headache days (MHDs) and monthly migraine days (MMDs) as well as change from baseline in both MHDs and MMDs. RESULTS: Among patients with CM, 140 mg erenumab was associated with a reduction of 1.2 MHD (p = .092) and a reduction of 1.0 MMD (p = .174) compared to onabotulinumtoxinA at Week 12. Among onabotulinumtoxinA-naïve patients, erenumab was associated with a reduction of 1.8 MHD (p = .026) and 1.4 MMD (p = .080) at Week 12. Among patients that had received ≥3 prior preventive treatments, the odds ratios comparing erenumab vs onabotulinumtoxinA were 1.7 for ≥50% responder rates based on reductions in MHD (p = .155) and 1.7 for ≥50% responder rates based on reductions in MMD (p = .140). CONCLUSION: These findings suggest directional benefits (although not reaching the threshold of statistical significance) associated with erenumab vs onabotulinumtoxinA for the preventive treatment of CM. Evidence from this study may inform healthcare stakeholders in treatment selection and optimization for patients with CM.

The impact of diabetic neuropathy on the distal versus proximal comparison of weakness in lower and upper limb muscles of patients with type 2 diabetes mellitus: a cross-sectional study.

OBJECTIVES: This study aimed to determine the impact of diabetic neuropathy (dNP) on the distal versus proximal comparison of weakness in lower and upper limb muscles of patients with type 2 Diabetes Mellitus (T2DM). METHODS: 19 healthy male controls without neuropathy (HC) and 35 male T2DM patients, without dNP (n=8), with sensory dNP (n=13) or with sensorimotor dNP (dNPsm; n=14), were enrolled in this study. Maximal isometric (IM) and isokinetic (IK) muscle strength and IK muscle endurance of the dominant knee, ankle and elbow, and maximal IM handgrip strength were measured by means of dynamometry. RESULTS: Ankle muscle endurance was lower compared to the knee, independently of dNP (p<0.001). Maximal IK ankle muscle strength was also lower compared to the knee, albeit only in dNPsm (p=0.003). No differences were found between maximal IM handgrip and elbow strength. CONCLUSIONS: Our results suggest an impact of T2DM -with or without dNP- on lower limb muscle strength more distally than proximally, while this was not observed in the upper limb. The gradient of dNP seemed to be a determining factor for the maximal muscle strength, and not for muscle endurance, in the lower limb.

The impact of sensory and/or sensorimotor neuropathy on lower limb muscle endurance, explosive and maximal muscle strength in patients with type 2 diabetes mellitus.

AIMS: The purpose of this study was to investigate the impact of diabetic neuropathy (dNP) on lower limb endurance, explosive and maximal muscle strength in patients with Type 2 Diabetes Mellitus (T2DM). METHODS: Fifty-four participants, aged between 55 and 85, were enrolled in this observational comparative study. The patients with T2DM had an average HbA1c of 7.4% (±1.03) and diabetes duration of 13 years. Participants were classified by means of electroneuromyography as T2DM without dNP (dNP-; n = 8), T2DM with sensory dNP (dNPs; n = 13), T2DM with sensorimotor dNP (dNPsm; n = 14), and healthy controls without neuropathy (C; n = 19). Maximal muscle strength and muscle endurance of the dominant knee and ankle were measured by dynamometry, while explosive muscle strength was evaluated by mechanography. RESULTS: Muscle endurance "total work" in knee extension and ankle plantar flexion was higher in the healthy controls compared to dNP-, dNPs and dNPsm, in knee flexion compared to dNPs and dNPsm, and in ankle dorsiflexion compared to dNPsm only (p<0.05). Furthermore, relative explosive muscle strength "total power/body weight" and relative maximal muscle strength "peak torque/lean body mass of the dominant leg" considering knee flexion, ankle plantar flexion and dorsiflexion, were higher in healthy controls compared to the dNPsm group, and for maximal muscle strength ankle dorsiflexion even between dNP- and dNPsm (p < 0.05). CONCLUSIONS: Muscle endurance is impaired in patients with T2DM, independent of the presence of dNP. Explosive and maximal muscle strength are more likely affected by the presence and severity of dNP.

Magnetic resonance angiography of the circle of Willis in migraine patients.

We analysed records of 244 consecutive adult outpatients who presented at our neurological polyclinic between 1996 and 2001 with migraine and who underwent a MRA of the circle of Willis. In 80 cases, a definitive migraine diagnosis according to the International Headache Society criteria (1988) could be retrieved from the patient records. Of these, 63 patients had migraine without aura and 17 patients had migraine with aura. Two MRA procedures were abrupted because of claustrophobia and another two MRA studies were unreliable because of movement artefacts. In only one patient of the remaining 240, an aneurysm was suspected with MRA. However, a conventional angiography did not confirm any cerebrovascular abnormality. All other exams were considered normal. This retrospective study argues against a systematic screening of migraine patients with MRA.

Efficacy of flow- vs impedance-guided autoadjustable continuous positive airway pressure: a randomized cross-over trial.

STUDY OBJECTIVES: Autoadjustable continuous positive airway pressure (CPAP) devices are increasingly used in the treatment of obstructive sleep apnea (OSA). Since different measurements of upper airway obstruction are applied, it is uncertain whether these devices are equally effective in controlling sleep-disordered breathing. Hypothesizing that differences in therapeutic efficacy were to come out, we compared the performance of the AutoSet device (ResMed; Sydney, Australia), which features autoadjustable positive airway pressure (APAP) guided by detection of flow limitation (APAPfl), with the SOMNOsmart device (Weinmann; Hamburg, Germany), which features APAP guided by the forced oscillation technique (APAPfot). DESIGN: A double-blind, randomized, cross-over trial. SETTING: The sleep disorders center and sleep laboratory of a university hospital. PATIENTS AND INTERVENTIONS: An overnight CPAP autotitration procedure was performed in 30 patients with OSA. A split-night protocol allowed that each patient used both devices. MEASUREMENTS AND RESULTS: Using polysomnography, sleep, indexes of sleep-disordered breathing, snoring, and CPAP levels were recorded. No significant differences were found in conventional sleep variables. While the apnea-hypopnea index (AHI) was lower with APAPfl (3.5 +/- 5.6/h) as compared to APAPfot (9.9 +/- 31.0/h), the difference was not statistically significant (mean +/- SD). The snoring index, however, was significantly lower with APAPfl (35.3 +/- 53.7/h vs 111.6 +/- 175.4/h, respectively; p = 0.01). The median and 95th percentile pressure levels rose from wakefulness to sleep in APAPfl, but decreased in APAPfot. Higher pressure variability was present in the latter method. CONCLUSIONS: These findings suggest that the APAPfl is superior to APAPfot in the control of snoring. While a lower AHI was achieved with APAPfl, at the expense of a higher median pressure but less pressure variability, the difference with APAPfot was not statistically significant.

Comfort and pressure profiles of two auto-adjustable positive airway pressure devices: a technical report.

STUDY OBJECTIVES: The purpose of this study was to compare comfort parameters and pressure profiles of the AutoSet (Resmed) and the SOMNOsmart (Weinmann), two auto-adjustable positive airway pressure (APAP) devices. SETTING: The sleep disorders center of a university hospital. DESIGN: A single-blind randomized trial protocol was applied. A split night procedure allowed each patient to be treated in a crossover fashion with both APAP devices during one overnight study. PATIENTS AND METHODS: Fifty consecutive obstructive sleep apnea (OSA) patients were recruited. Each patient filled out an evaluation form for both devices after the study night. Visual analogue scales were used to score four comfort measures. Three CPAP outcomes generated by the devices (P50, P95 and Pmax) were assessed, compared with each other and correlated with the individually predicted CPAP (Ppred). RESULTS: Forty-five males and 5 females, mean age 53.0 years, body mass index 31.0, were included. The mean apnea-hypopnea index was 58.7, the mean arousal index was 54.3. Mean CPAP-compliance before the titration study was 4.9 h per night. Comparison of the two devices regarding the effect on the subjective sleep quality parameters showed no differences. The AutoSet pressure outcomes correlated significantly better with Ppred in comparison with the SOMNOsmart. The P50 and P95 but not the Pmax values were significantly lower in the SOMNOsmart as compared with the AutoSet (P50: 5.1+/-1.3 vs 7.1 +/- 1.9 mbar, P<0.0001; P95: 7.8+/-3.0 vs 9.6+/-1.9 mbar, P<0.0005; Pmax: 10.0+/-3.4 vs 10.8+/-1.8 mbar, NS). CONCLUSION: While the subjective tolerance of the two APAP machines was comparable, these devices were characterized by different pressure profiles. The pressure parameters of the AutoSet correlated better with Ppred than those of the SOMNOsmart.