Comparison of New Pharmacologic Agents With Triptans for Treatment of Migraine: A Systematic Review and Meta-analysis.

Importance: New therapeutic classes of migraine-specific treatment have been developed, including 5-hydroxytryptamine1F receptor agonists (lasmiditan) and calcitonin gene-related peptide antagonists (rimegepant and ubrogepant). Objective: To compare outcomes associated with the use of lasmiditan, rimegepant, and ubrogepant vs triptans for acute management of migraine headaches. Data Sources: The Cochrane Register of Controlled Trials, Embase, and PubMed were searched from inception to March 5, 2020. Study Selection: Double-blind randomized clinical trials examining current available migraine-specific acute treatments were included. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was applied to extract the data according to a predetermined list of variables of interest, and all network meta-analyses were conducted using a random-effects model. Main Outcomes and Measures: The primary outcome was the odds ratio (OR) for freedom from pain (hereafter referred to as pain freedom) at 2 hours after the dose, and the secondary outcomes were ORs for pain relief at 2 hours after the dose and any adverse events. Results: A total of 64 randomized clinical trials were included (46 442 participants; 74%-87% women; age range, 36-43 years). Most of the included treatments were associated with reduced pain at 2 hours compared with placebo. Most triptans were associated with higher ORs for pain freedom at 2 hours compared with lasmiditan (range: OR, 1.72 [95% CI, 1.06-2.80] to OR, 3.40 [95% CI, 2.12-5.44]), rimegepant (range: OR, 1.58 [95% CI, 1.07-2.33] to OR, 3.13 [95% CI, 2.16-4.52]), and ubrogepant (range: OR, 1.54 [95% CI, 1.00-2.37] to OR, 3.05 [95% CI, 2.02-4.60]). Most triptans were associated with higher ORs for pain relief at 2 hours compared with lasmiditan (range: OR, 1.46 [95% CI, 1.09-1.96] to OR, 3.31 [95% CI, 2.41-4.55]), rimegepant (range: OR, 1.33 [95% CI, 1.01-1.76] to OR, 3.01 [95% CI, 2.33-3.88]), and ubrogepant (range: OR, 1.38 [95% CI, 1.02-1.88] to OR, 3.13 [95% CI, 2.35-4.15]). The comparisons between lasmiditan, rimegepant, and ubrogepant were not statistically significant for both pain freedom and pain relief at 2 hours. Lasmiditan was associated with the highest risk of any adverse events, and certain triptans (rizatriptan, sumatriptan, and zolmitriptan) were also associated with a higher risk of any adverse events than the calcitonin gene-related peptide antagonists. Conclusions and Relevance: For pain freedom or pain relief at 2 hours after the dose, lasmiditan, rimegepant, and ubrogepant were associated with higher ORs compared with placebo but lower ORs compared with most triptans. However, the lack of cardiovascular risks for these new classes of migraine-specific treatments may offer an alternative to triptans.

Comparative Effectiveness and Tolerability of the Pharmacology of Monoclonal Antibodies Targeting the Calcitonin Gene-Related Peptide and Its Receptor for the Prevention of Chronic Migraine: a Network Meta-analysis of Randomized Controlled Trials.

Monoclonal antibodies (mAbs) acting on the calcitonin gene-related peptide (CGRP) or on its receptor are new therapeutic biologics to prevent chronic migraine (CM). Four mAbs acting on the CGRP or on its receptor are new therapeutic biologics to prevent CM. The aim of current network meta-analysis (NMA) was to compare the efficacy and acceptability of CGRP mAbs with onabotulinumtoxinA or topiramate for CM. We included randomized controlled trials (RCTs) examining CGRP mAbs and onabotulinumtoxinA or topiramate in patients with CM. All network meta-analytic procedures were conducted using the frequentist model. The primary outcomes were changes in the monthly migraine days and the 50% response rate. The safety was evaluated with acceptability (i.e., drop-out rate) and rate of any adverse event. This NMA of thirteen RCTs, which, in total, consisted of 5634 participants, demonstrated that a single 300 mg of eptinezumab (mean difference = - 2.60 days, 95% confidence intervals (95% CIs) = - 4.43 to - 0.77 compared with placebo) demonstrated the best improvement in monthly migraine days among all interventions. In addition, 675 mg fremanezumab in the first month followed by 225 mg in the second and third months (odds ratio (OR) = 2.96, 95% CIs = 2.20 to 3.97 compared to placebo) was associated with the best response rate among all the interventions. Monthly 140 mg erenumab (MD = - 2.50 days, 95% CIs = - 3.83 to - 1.17 compared with placebo) was the best choice for reducing the number of acute migraine-specific medication use days. The safety analysis revealed that loading dose of 240 mg galcanezumab and monthly 240 mg (OR = 0.43, 95% CIs = 0.22 to 0.84) was associated with the lowest drop-out rate; loading dose fremanezumab 675 mg and monthly 675 mg (OR = 1.44, 95% CIs = 1.10 to 1.89), loading dose of 240 mg galcanezumab and monthly 120 mg (OR = 1.37, 95% CIs = 1.02 to 1.84), and single dose of fremanezumab 675 mg (OR = 1.35, 95% CIs = 1.00 to 1.83) were associated with significantly higher rates of AEs than the placebo/control groups. Our NMA indicated that all four CGRP mAbs demonstrated excellent safety, acceptability, and efficacy profiles compared to the traditional prophylaxis for CM. However, because there are several limitations, the findings of the current NMA should be taken into consideration with caution.

The Morphological and Dynamic Changes of Ultrasound in the Evaluation of Effects of Oral Steroids Treatment for Patients with Carpal Tunnel Syndrome.

The role of oral steroids in carpal tunnel syndrome (CTS) remains elusive. This study aims to depict the ultrasound findings and conceivable mechanisms in relation to the efficacy of oral steroids for patients with CTS by measuring the morphological and motion changes in the median nerve. In this study, CTS patients were randomized to the oral steroid group (14 participants and 22 wrists) or nicergoline group (22 participants and 35 wrists) for 4 weeks. Both treatment arms were given global symptom score (GSS) measurements and completed an ultra-sound at baseline and at 2- and 4-weeks post-treatment. In the nerve conduction study (NCS), distal motor latency (DML) was used to assess the treatment response at baseline and 4 weeks post-treatment. The cross-sectional area (CSA) and amplitude (AMP) evaluated by the maximum lateral sliding displacement represented the morphological and dynamic changes in the median nerve, respectively. The results showed that AMP, CSA, GSS, and DML were significantly im-proved in the steroid group, as compared to the nicergoline group at weeks 2 and 4 (p < 0.05). The mean improvement in ultrasound parameters CSA (15.03% reduction) and AMP (466.09% increase) was better than the DML (7.88% reduction) parameter of NCS, and ultrasound changes were detectable as early as 2 weeks after oral steroid administration. Ultrasounds can serve as a tool for the quantitative measurement of treatment effects and can potentially elucidate the pathogenesis of CTS in a non-invasive and more effective manner.

Evidence of Potential Mechanisms of Acupuncture from Functional MRI Data for Migraine Prophylaxis.

PURPOSE OF REVIEW: To summarize the clinical neuroimaging evidence pertaining to the potential mechanisms of acupuncture for migraine prophylaxis. RECENT FINDINGS: From a descriptive perspective, converging evidence from recent neuroimaging studies, mainly from functional MRI (fMRI) studies, has demonstrated that when compared with sham acupuncture, verum acupuncture could normalize the decrease of the functional connectivity of the rostral ventromedial medulla-trigeminocervical complex (RVM/TCC) network, frontal-parietal network, cingulo-opercular networks, and default mode network and could normalize sensorimotor network connectivity with sensory-, affective-, and cognitive-related brain areas. These areas overlap with those of the pain matrix. Verum acupuncture works in a more targeted and unique manner compared with sham acupuncture in patients with migraine. These findings from neuroimaging studies may provide new perspectives on the validation of acupoints specificity and confirm the central modulating effects of acupuncture as a migraine prevention treatment. However, the exact mechanism by which acupuncture works for migraine prophylaxis remains unclear and warrants investigation. Future studies with larger sample sizes are still needed to confirm the current results and to further evaluate the complex and specific effects of acupuncture by analyzing different stimulus conditions, such as verum vs. sham acupuncture, deqi vs. no deqi, different acupuncture points or meridians, and different manipulation methods. Moreover, instead of focusing on the changes in a single area of the brain, researchers should focus more on the relationships among the functional connectivity network of brain areas such as the RVM/TCC, thalamus, anterior cingulate cortex (ACC), superior temporal gyrus (STG), and supplementary motor area (SMA) to explore the underlying mechanism of the effects of acupuncture.

Laser Acupuncture for Carpal Tunnel Syndrome: A Single-Blinded Controlled Study.

Objectives: This study aimed to compare the efficacy of laser acupuncture (LA) treatment with that of placebo LA treatment in patients with idiopathic, mild-to-moderate carpal tunnel syndrome (CTS), as measured by subjective symptom assessments and objective changes in nerve conduction studies (NCSs). Design: A randomized, single-blinded, controlled study. Settings: A Teaching Hospital in the Taichung, Taiwan between March 2013 and November 2013. Subjects: 84 consecutive treatment-naive patients with CTS. Interventions: Participants were randomly divided into two treatment arms: (1) LA, administered at traditional Chinese acu-points on the affected side, once a day, 5 times a week, for 4 weeks (N = 43); and (2) placebo LA, administered using the same device and protocol, with the LA device switched off (N = 41). Outcome measures: Patients completed the Global symptom score (GSS) at baseline and two and four weeks later. The primary outcome was changes in GSS. NCSs were performed at baseline and repeated at the end of the study as a secondary outcome. Results: There was a significantly greater reduction in GSS in the LA group than in the placebo group at week 2 (-9.30 ± 4.94 vs. -2.29 ± 4.27, respectively, P < 0.01) and at week 4 (-10.67 ± 5.98 vs. -2.90 ± 5.61, respectively, P < 0.01). However, NCSs did not show significant difference between the two groups. Conclusions: LA may be more effective than placebo LA in the treatment of mild-to-moderate idiopathic CTS in terms of subjective measurement. For patients who fear needle-based treatment, such as acupuncture or local injections, or those who do not opt for early surgical decompression, LA treatment can be considered as an effective and alternative form of acu-points stimulation therapy.

Integrated therapy decreases the mortality of patients with polymyositis and dermatomyositis: A Taiwan-wide population-based retrospective study.

ETHNOPHARMACOLOGICAL RELEVANCE: The issue of whether integrated treatment with conventional medicine (CM) and herbal medicine (HM) can reduce mortality in patients with polymyositis/dermatomyositis (PM/DM) had not been addressed. AIM OF THE STUDY: In this study, we investigated the effect of integrated therapy on mortality in a retrospective PM/DM cohort in the Taiwan National Health Insurance Research Database (NHIRD). MATERIALS AND METHODS: Patients with PM/DM were retrospectively enrolled from the PM/DM Registry of Catastrophic Illnesses cohort in the Taiwan NHIRD between 1997 and 2011. The patients were divided into an integrated medicine (IM) group that received CM and HM and a non-IM group that received CM alone. The Cox proportional hazards regression model and Kaplan-Meier method were used to evaluate the hazard ratio (HR) for mortality. RESULTS: Three hundred and eighty-five of 2595 patients with newly diagnosed PM/DM had received IM and 99 had received non-IM. The adjusted HR for mortality was lower in the IM group than in the non-IM group (0.42, 95% confidence interval 0.26-0.68, p < 0.001). The adjusted HR for mortality was also lower in the IM group that had received CM plus HM than in the group that received CM alone (0.48, 95% confidence interval 0.28-0.84, p < 0.05). The core pattern of HM prescriptions integrated with methylprednisolone, methotrexate, azathioprine, or cyclophosphamide to decrease mortality included "San-Qi" (Panax notoginseng), "Bai-Ji" (Bletilla striata), "Chen-Pi" (Citrus reticulata), "Hou-Po" (Magnolia officinalis), and "Dan-Shan" (Salvia miltiorrhiza). CONCLUSION: Integrated therapy has reduced mortality in patients with PM/DM in Taiwan. Further investigation of the clinical effects and pharmaceutical mechanism involved is needed.

Integrated therapy improve urinary total protein in patients with lupus nephritis: A case report.

OBJECTIVES: To report on the potential effectiveness of Chinese herbal medicine (CHM) as part of an integrated treatment for lupus nephritis. CLINICAL FEATURES AND OUTCOME: A 55-year-old female with systemic lupus erythematosus had experienced bilateral lower-limbs edema for half a year. Her urinary total protein (M-TP) was 1367.9 mg/24 h. Lupus nephritis (LN) was suspected by the Division of Rheumatology without a renal biopsy. Oral corticosteroid medication did not improve the edema; therefore, the patient requested CHM for integrated therapy, and was subsequently treated for seven months with a modified CHM prescription mainly composed of Zhi-Bo-Di-Huang-Wan, Gui-Shao-Zhi-Mu-Tang, and Zhu-Ling-Tang. After three days of CHM, her bilateral lower-limbs edema significantly improved, and after 143 days, her M-TP decreased from 1367.9 mg/24 h to 143.6 mg/24 h. CONCLUSIONS: Integrated therapy could significantly improve proteinuria by reducing this LN patients' urinary total protein, which further implies that CHM may have a protective effect against the progression of LN in this patient.