Efficacy and Safety of Chuanxiong Qingnao Granule in Patients with Migraine: A Randomized, Double-Blind, Placebo-Controlled Trial

Objective. To evaluate the efficacy and safety of Chuanxiong Qingnao Granule (CQG) to treat migraine. Method. This study was a randomized, double-blind, placebo-controlled trial. All migraineurs were recruited and randomly assigned into a treatment group treated with CQG and a control group treated with a placebo. The whole research process included a 4-week baseline, 12-week intervention, and 12-week follow-up. The primary outcome was responder rate, defined as the percentage of migraineurs with 50% or more reduction in the frequency of migraine attack during treatment and posttreatment period compared with the baseline. The secondary outcomes were the number of migraine days, migraine attack frequency, visual analogue scale (VAS), Fatigue Severity Scale (FSS), Hamilton Depression Scale (HAMD), and Migraine Disability Assessment (MIDAS). Results. A total of 346 migraineurs completed the research and were included in the intention-treatment analyses. The response rates differed significantly between the treatment group and the control group (71.5% vs. 12.1% at week 12 and 83.1% vs. 3.4% at week 24). Attack frequency, days of headache attack, VAS, FSS, HAMD, and MIDAS decreased at week 12 in both groups with more reduction in the treatment group ( P < 0.001 ). No severe adverse events were observed in this trial. Conclusion. Chuanxiong Qingnao Granule can significantly improve headache symptoms in patients with migraine while improving disability, fatigue, and depression with a good safety profile.

Prophylactic Heme Arginate Infusion for Acute Intermittent Porphyria

Objectives: This study aimed to evaluate the efficacy of long-term weekly prophylactic heme arginate (HA) infusions in reducing attack frequency and severity in female AIP patients.Methods: We report the results of five female AIP patients with frequent recurrent attacks (&gt;9/year) before and after institution of weekly prophylaxis with heme arginate (3 mg/kg body weight). All five cases had confirmed disease-associated mutations in the porphobilinogen deaminase gene, and all had received genetic and clinical counseling about AIP.Results: In the five included patients, average annual attack rate (AAR) in the year prior to HA prophylaxis was 11.82 (range 9.03–17.06), and average total HA usage was 32.60 doses (range: 13.71–53.13). After 2.58–14.64 years of HA prophylaxis, average AAR was reduced to 2.23 (range 0.00–5.58), and attack severity (i.e., doses required per attack) was reduced from 2.81 to 1.39 doses/attack. Liver and renal function remained stable during weekly administration of HA prophylaxis. The most common complications were port-A catheter-related events. No other complications or safety concerns occurred with long-term use of HA prophylaxis.Conclusion: Our study demonstrated women with AIP receiving weekly prophylactic HA infusions resulted in fewer episodes that required acute HA treatment while maintaining stable renal and liver function. Weekly prophylactic HA infusions effectively prevent frequent porphyric attacks and reduce attack severity.

Description and Analysis of a Novel Subtype of the Anti-Synthetase Syndrome Characterized by Frequent Attacks of Fever and Systemic Inflammation in a Single-Center Cohort Study

ObjectivesThe aim of this study was to investigate anti-synthetase syndrome (ASyS) patients who presented with recurrent episodes of fever and systemic inflammation.MethodsA retrospective cohort of Chinese ASyS patients (n=126) in our center (between January 2013 and January 2020) was included. Patients presenting with concomitant autoimmune rheumatic diseases or malignancies were subsequently excluded. The number of non-infectious fever attacks and attack frequency were recorded and calculated. Patients with two or more attacks and within the upper three quartiles of attack frequency were defined as high-inflammation group. Univariate and multivariate analyses were carried out to characterize the high-inflammation subtype.ResultsOut of 113 eligible patients with an average of 5 years follow up, 25 patients were defined as the high-inflammation group (16 for anti-Jo1, 9 for anti-PL7), with an average of 1.12 attack/patient-year. Compared to low-inflammation group (0–1 attack only and a frequency lower than 0.5 attack/patient-year), the high-inflammation group had higher occurrence of fever and rapid progressive interstitial lung disease (RPILD) as the first presentation (84% vs. 21% and 40% vs. 9%, respectively, both p&lt;0.01). Anti-PL-7 was related to the more inflammatory phenotype (p=0.014). Cumulative disease-modifying agent exposures (&gt;=3) were much higher in the high-inflammation group (60% vs. 26%), while biological agents, i.e., rituximab and tocilizumab, showed better “drug survival” for Jo-1+ and PL-7+ ASyS patients with high inflammation, respectively, in our cohort.ConclusionsASyS with recurrent systemic inflammatory episodes reflects a subtype of more aggressive and refractory disease in the spectrum of ASyS. Increased awareness of this subtype might lead to more appropriate management.

Effects of Korean Medicine Treatment focusing on Acupotomy of headache: A Case Report of Four Patients

Background: The aim of this study was to report the effect of acupotomy for patients with headache. Methods: Four patients with headache were treated with acupotomy. The improvement of symptoms was evaluated by numeric rating scale(NRS), Headache impact test-6(HIT-6) and headache attack frequency. Results: The numeric rating scale score and headache attack frequency decreased throughout the treatment period. No side effects were observed during treatment. Conclusion: Acupotomy had shown a positive clinical effect in the treatment of a headache in this case series. Further studies are required for its application on various headache.

Effect of COVID-19 on hereditary angioedema activity and quality of life

Background: The demonstration that severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) enters the cell via the angiotensin-converting enzyme 2 receptor has raised concerns that, in hereditary angioedema (HAE), a disease characterized by bradykinin-mediated angioedema attacks, coronavirus disease 2019 (COVID-19) may trigger angioedema attacks, increase the frequency and/or severity of attacks, or cause more severe symptoms of COVID-19. Objective: The objective was to evaluate the severity of COVID-19 in patients with HAE, the course of HAE attacks, angioedema activity, and the quality-of-life scores during COVID-19 pandemic. Methods: Patients diagnosed with HAE for at least 6 months were included in the study. The 7-day Angioedema Activity Score and the Angioedema Quality of Life (AE-QoL) Questionnaire were first completed at the onset of the pandemic between March 12 and June 1, 2020, then during SARS-CoV-2 infection, and in the third month after recovering from COVID-19. Results: Ten of 67 patients with HAE (14.9%) were diagnosed with COVID-19. The median (interquartile range) age of the 10 patients diagnosed with COVID-19 was 35.5 years (28.0‐55.0 years). Six of the 10 patients (60%) were women. During COVID-19, five of the 10 patients (50%) had no angioedema attack. Two patients with severe HAE experienced a significant increase in angioedema activity during COVID-19 compared with their basal activity scores. The remaining three patients had a similar or lower attack frequency than their basal level. Four (40%) of the 10 patients had a relative increase in their attacks during the convalescence period. There was no statistically significant difference among pre-COVID-19, during COVID-19 and post-COVID-19 periods in function, mood, fear and/or shame, nutrition, and total scores of the AE-QoL Questionnaire although the fear dimension was relatively more affected (p = 0.06). Conclusion: Although the sample size was small, analysis of our data supported that the symptoms of COVID-19 were not more severe in HAE. Also, there was no significant difference in the AE-QoL Questionnaire scores, the frequency, and severity of angioedema attacks during the course of COVID-19 in the patients with HAE.

Efficacy and safety of canakinumab for colchicine-resistant or colchicine-intolerant familial Mediterranean fever: A single-centre observational study

ABSTRACT Objectives To evaluate the efficacy and safety of canakinumab in Japanese patients with colchicine-resistant or colchicine-intolerant familial Mediterranean fever (FMF) in a real-world clinical setting. Methods We reviewed 13 Japanese FMF patients to whom canakinumab was introduced during the period of October 2017 to December 2020. All patients were diagnosed as FMF according to Tel-Hashomer criteria. We performed genetic analyses for Mediterranean fever or MEFV by targeted next-generation sequencing. Efficacy was assessed by attack frequency and the percentage of patients who achieved attack improvement at 24 weeks. Safety was assessed by adverse events observed during canakinumab treatment. Results The median duration and follow-up of canakinumab treatment were 13 and 16 months, respectively. The median attack frequency was 0.50 [0.30–1.00] at 24 weeks, which was a significant decrease from 2.00 [0.85–2.88] at the time of induction (p = .019). There were three patients (23%) with complete resolution of attacks at 24 weeks. No serious adverse events were observed. However, one patient had small intestinal ulceration which led to the discontinuation of canakinumab. Conclusions Although the number of cases is small, this study suggests that canakinumab is efficacious and safe for use in Japanese patients with colchicine-resistant or colchicine-intolerant FMF in a real-world clinical setting in Japan.

The chronobiology of migraine: a systematic review

Background The paroxysmal nature of migraine is a hallmark of the disease. Some patients report increased attack frequency at certain seasons or towards the end of the week, while others experience diurnal variations of migraine attack onset. This systematic review investigates the chronobiology of migraine and its relation to the periodicity of attacks in existing literature to further understand the oscillating nature of migraine. Main body PubMed and Embase were systematically searched and screened for eligible articles with outcome measures relating to a circadian, weekly or seasonal distribution of migraine attacks. We found that the majority of studies reported morning hours (6 am–12 pm) as the peak time of onset for migraine attacks. More studies reported Saturday as weekly peak day of attack. There was no clear seasonal variation of migraine due to methodological differences (primarily related to location), however four out of five studies conducted in Norway reported the same yearly peak time indicating a possible seasonal periodicity phenomenon of migraine. Conclusions The findings of the current review suggest a possible role of chronobiologic rhythms to the periodicity of migraine attacks. Future studies are, however, still needed to provide more knowledge of the oscillating nature of migraine.

Altered Metabolites in the Occipital Lobe in Migraine Without Aura During the Attack and the Interictal Period

Background: Although there have been many magnetic resonance spectroscopy (MRS) studies of migraine, few have focused on migraines during an attack. Here, we aimed to assess metabolite changes in the brain of patients with migraine, both during an attack and in the interictal phase.Methods: Six patients (one man and five women, mean age: 39 ± 10 years) with migraine without aura during the attack (MWoA-DA), 13 patients (three men and 10 women, mean age: 31 ± 9 years) with migraine without aura during the interictal period (MWoA-DI), and 13 healthy controls (HC) (four men and nine women, mean age: 31 ± 9 years) were studied. All subjects underwent an MRS examination focusing on the occipital lobe. Metabolite changes were investigated among three groups.Results: The MWoA-DA patients had lower glutathione/total creatine ratio (GSH/tCr) than the MWoA-DI patients and HC. Furthermore, MWoA-DI patients showed lower total choline/total creatine ratio (tCho/tCr) than those in the other two groups. The GSH/tCr ratio was positively correlated with attack frequency in the MWoA-DI group. The tCho/tCr ratio was positively correlated with attack frequency and Migraine Disability Assessment Scale (MIDAS) scores in the MWoA-DA group.Conclusion: The present study suggests the existence of distinct pathophysiological states between the MWoA-DA and MWoA-DI groups. Neuronal dysfunction is a possible predisposing factor for migraine attack onset, along with oxidative stress and inflammation.

POS1350 FAMILIAL MEDITERRANEAN FEVER DURING PREGNANCY: A 26 CASE SERIES WITH 38 PREGNANCIES

Background:Familial Mediterranean Fever (FMF) is an autoinflammatory disease characterized by recurrent attacks with autosomal recessive inheritance. FMF usually occurs in young age; most patients (90%) begin to suffer from their first attack before 20 years of age. Pregnancy can occur frequently during the course of the disease, as women of reproductive age are affected by the disease.Objectives:In this study, it was aimed to retrospectively examine the demographic, genetic, and clinical features (frequency of attacks during pregnancy, duration of attacks, treatment of attacks) of 26 cases who were followed up with a diagnosis of FMF in the last five years and experienced pregnancy.Methods:A total of twenty-six female FMF cases experienced pregnancy and diagnosed or followed up in our rheumatology center between 2015-2020 were included in the study. All patients were diagnosed according to Tel-Heshomer criteria. All data and follow-up visit records of the patients were retrospectively recorded by the rheumatologist. Patients were followed up by an obstetrician working in the same center during pregnancy. The demographic and genetic characteristics of the patients, the treatment used, the duration and characteristics of the attack during pregnancy, and the treatment they received during the attack were recorded retrospectively. Data processing and analysis conducted with SPSS 22 for Windows.Results:During the follow-up period, a total of 38 pregnancies were observed in 26 female cases. When the genetic mutation tests of all patients were examined, 61% were M694, 15% were V726, 11% were M680I positive and compound mutation was detected in 42% of the patients. The mean age of the patients was 30±7.8, the disease duration was 9.8± 5.4 years, the follow-up period was 38±14 months, the attack frequency during pregnancy was 3.6± 1.7 and the attack duration was 14± 9.8 hours. Considering the clinical features, fever was seen in 92.3%, abdominal pain 96.1%, chest pain 88.4%, arthritis 11.5% and other symptoms seen in 26% during attacks of pregnant FMF patients. All patients used 1 gram of colchicine regularly throughout pregnancy. Steroids were used in 11.5% of patients and non-steroid anti-inflammatory drugs in 53.8% of patients during the attack. Anakinra was used in 11.5% of the cases except for the first trimester following a written consent obtained from the patients.In 10.5% of 38 pregnancies, spontaneous abortion was observed in the early period, 7.8% of pregnancies resulted in preterm delivery before 32 weeks. In addition, 81.5% of pregnancy completed the planned period and resulted in a healthy birth. Cesarean section was performed in 4 patients and normal delivery procedure in 27 patients. Major malformation-anomaly was not observed in any baby. When patients using colchicine (73%) irregularly and less than 1 gram (26.9%) before pregnancy were compared in terms of attack frequency and duration, the group using regular medication had significantly fewer and shorter attacks (p<0.05).Three colchicine resistant patients with M694 homozygous mutation became pregnant under anakinra treatment. A total of five pregnancies were followed in three cases. No medication was used in these patients in the first trimester. As of the second trimester, 100mg/day for 3 days of anakinra was administered in these patients after obtaining an informed consent. In this patient group, no obstetric problem was observed during and after pregnancy, and healthy deliveries were realized.Conclusion:Pregnancy is common in FMF patients of reproductive age. Disease and relapse treatment during pregnancy is still a problem due to the limited number of medications that can be used for treatment. Further studies required to verify safety of Anakinra in refractory FMF cases. There is a need to develop options for the prevention and treatment of attacks during pregnancy.Disclosure of Interests:None declared

Assessing the cost and quality-of-life impact of on-demand‐only medications for adults with hereditary angioedema

Background: Novel subcutaneous (SC) prophylactic therapies are transforming the treatment landscape of hereditary angioedema (HAE). Although questions are being raised about their cost, little attention has been paid to the cost and quality of life (QoL) impact of using on-demand‐only medications. Objective: We assessed the overall economic burden of on-demand‐only treatment for HAE and compared patient QoL with patients who received novel SC prophylactic therapies. Methods: US Hereditary Angioedema Association members were invited to complete an anonymous online survey to profile attack frequency, treatment use, and the presence of comorbidities as well as economic and socioeconomic variables. We modeled on-demand treatment costs by using net pricing of medications in 2018, indirect patient and caregiver costs, and attack-related direct billed costs for emergency department admissions, physician office visits, and/or hospitalizations. QoL was assessed by using the Angioedema Quality of Life questionnaire. Results: A total of 1225 patients (31.4%) responded. Of these, 737 adults with HAE (type I or II) met the inclusion criteria and completed the survey. Per patient/year direct costs associated with modeled on-demand‐only treatment totaled $363,795, with additional indirect socioeconomic costs of $52,576 per patient/year. The greatest improvement in QoL was seen in patients who used novel SC prophylactic therapies, with a 59.5% (p < 0.01) improvement in median impairment scores versus on-demand‐only treatment. In addition, patients who used novel SC prophylactic therapies reported a 77% reduction in the number of attacks each year when compared with those who used on-demand‐only treatment. Conclusion: Our real-world patient data showed the cost and QoL burden of HAE treatment with on-demand‐only therapy. Use of novel SC prophylaxis can lead to sizeable reductions in attack frequency and statistically significant and clinically relevant improvements in QoL. These data could be useful to clinicians and patients as they consider therapy options for patients with HAE.