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.

Risperidone for Extended-Release Injectable Suspension (Perseris)

CADTH recommends that Perseris should be reimbursed by public drug plans for the treatment of schizophrenia in adults if certain conditions are met. Perseris should be covered by public drug plans in a similar manner to other long-acting injectable atypical antipsychotic drugs for the treatment of adults with schizophrenia. Perseris should only be reimbursed if the total monthly dose is not more than 120 mg and is not used in combination with other long-acting injectable antipsychotic drugs. Perseris should not cost more than other long-acting injectable (LAI) atypical antipsychotic drugs.

AB0483 CAN WE PREDICT WHICH PATIENTS WITH SPONDYLOARTHRITIS WILL NEED DOSE ESCALATION OF SECUKINUMAB TO 300 mg MONTHLY?

Background:Secukinumab is a fully human monoclonal antibody against interleukin-17A, approved in several countries for the treatment of ankylosing spondylitis (AS) and psoriatic arthritis. It is known that some patients benefit from increasing the monthly dose of secukinumab from 150mg, the most commonly used dose, to 300mg. However, the baseline clinical characteristics that differentiate these patients are not yet fully understood.Objectives:This study aimed to investigate whether there are any variables at the beginning of biologic therapy that might predict a greater probability of having to increase the dose of secukinumab to 300mg in order to obtain a response to treatment.Methods:This is a retrospective cohort study, including all the spondyloarthritis and psoriatic arthritis patients under secukinumab at our Rheumatology Department and registered in the national database (Reuma.pt).Demographic, clinical and laboratorial characteristics and disease activity measures were collected from the first visit before the patient began secukinumab. For comparison between the 2 groups, continuous variables were analyzed using Mann-Whitney U and T-tests and categorical variables were analyzed using a Chi-square test. Multivariate regression analyses assessed the impact of selected variables on the need to increase the dose of secukinumab to 300mg.Results:Thirty-two patients with a mean age of 53±11.96 years were included, 19 (58%) were females and 16 (48.5%) had psoriasis. Twenty-seven (81.8%) patients were under a nonsteroidal anti-inflammatory drug (NSAID), 11(33.3%) were under corticosteroid and 11(33.3%) were under conventional synthetic disease-modifying antirheumatic drug (csDMARD); 25 (75,8%) had previously been treated with a biological disease-modifying antirheumatic drug (bDMARD). The mean patient baseline VAS and physician baseline VAS were 74,39±19,77 and 47,55±23,38, respectively; the mean erythrocyte sedimentation rate (ESR) and C-Reactive Protein (CRP) were 26,33±22,62 mm/hr and 10,81±16,88 mg/dL, respectively; the mean swollen joint count (SJC) and tender joint count (TJC) were 1,30±1,63 and 3,67±3,14, respectively; the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) were 6,18±2,06 and 3,41±0,84, respectively; the mean Bath Ankylosing Spondylitis Metrological Index (BASMI) and Bath Ankylosing Spondylitis Functional Index (BASFI) were 4,22±1,58 and 6,28±2,53, respectively; the mean Maastrich Ankylosing Spondylitis Enthesitis Score (MASES) was 2,85±3,23.Nineteen patients (57.6%) had the dose of secukinumab increased to 300mg. At the baseline visit, the group of patients which had their secukinumab monthly dose increased to 300mg were more frequently men (12 vs 2, p=0.005) and had psoriasis (12 vs 4, p=0.049). On the other hand, these patients also exhibited lower MASES values (2±1.089 VS 4±0.501, p=0.022).A regression analysis was conducted, estimating the relationships between the outcome binary variable of the monthly dose of secukinumab and the following predictors: gender, psoriasis, MASES value and use of corticosteroid. Female gender (OR 0.070, CI95% 0.005-0.890; p=0.040) and absence of psoriasis (OR 0.104, CI95% 0.011-0.952; p=0.045) were predictors for maintaining secukinumab at a dose of 150mg monthly.Conclusion:Our data suggest that the most common characteristics of patients in need of increasing the monthly dose of secukinumab from 150 to 300 mg to achieve a better treatment response are: male gender, coexistence of psoriasis and lower MASES value at baseline. The first two variables remained statistically significant in a multivariate model of regression analysis. Nonetheless, we insist it is of paramount importance to conduct larger studies to confirm these findings.References:[1]Deodhar A, et all. Long-term safety of secukinumab in patients with moderate-to-severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. Arthritis Res Ther. 2019 May 2;21(1):111.Disclosure of Interests:None declared.

Antimicrobial photodynamic therapy in voice rehabilitation of patients after laryngectomy

The article is devoted to the problem of voice rehabilitation of patients after laryngectomy. Modern possibilities of repairing laryngeal vocal function, methods for extending the lifetime of voice prostheses are considered. The author’s method of prevention of infection of vocal prostheses using the antimicrobial photodynamic therapy (PDT) with chlorin-type photosensitizer Radagel is presented. Performing antimicrobial PDT of vocal prostheses increased the average operating time to 11.9 months compared to the control group (6.8 months), where a monthly dose of 150 mg of fluconazole was used for prevention. The method developed by the authors makes it possible to significantly extend the lifetime of vocal prostheses, is devoid of adverse events, is well tolerated by patients.

The use of erenumab for preventing migraine

Background: In 2018, calcitonin gene-related peptides (CGRP) were approved in the United States as the first class of specific migraine prevention drugs. Objectives: To analyze the efficacy and therapeutic safety of erenumab for preventing migraine. Methods: A narrative literature review was carried out by researching in the PubMed/MEDLINE and SciELO databases, using the descriptor “migraine disorders” and the keyword “erenumab” combined by the Boolean operator AND. Eight articles were selected, between 2017 and 2020. Results: The pathophysiology of migraine is related to CGRP through nociceptive modulation in the trigeminovascular system. Therefore, erenumab was developed, which is a human monoclonal antibody that binds selectively and potently to the canonical receptor of CGRP and acts as an antagonist of CGRP. Evidence indicates that the monthly dose of 70mg or 140mg reduces the frequency, quality and intensity of acute and chronic migraines. Studies report a decrease of two to six days of migraine using erenumab. The same adverse reactions occurred in both placebo and experimental groups, including upper respiratory tract viral infection, pain at the injection site and nausea. Conclusions: Erenumab is a promising drug, because it showed efficacy in the first days of treatment, absence of significant side effects and low rate of discontinuation. Aspects such as safety, effect durability, impact on quality of life and cost require further research.

A Randomized Trial of Strategies Using Darbepoetin Alfa To Avoid Transfusions in CKD

BackgroundExposure to high doses or a high cumulative dose of erythropoiesis-stimulating agents (ESAs) may contribute to cardiovascular events in patients with CKD and anemia. Whether using a low fixed ESA dose versus dosing based on a hemoglobin-based, titration-dose algorithm in such patients might reduce risks associated with high ESA doses and decrease the cumulative exposure—while reducing the need for red blood cell transfusions—is unknown.MethodsIn this phase-3, randomized trial involving 756 adults with stage-3 to -5 CKD and anemia, we evaluated incidence of red blood cell transfusions for participants randomized to receive darbepoetin given as a fixed dose (0.45 µg/kg every 4 weeks) versus administered according to a hemoglobin-based, titration-dose algorithm, for up to 2 years. Participants received transfusions as deemed necessary by the treating physician.ResultsThere were 379 patients randomized to the fixed-dose group, and 377 to the titration-dose group. The percentage of participants transfused did not differ (24.1% and 24.4% for the fixed-dose and titration-dose group, respectively), with similar time to first transfusion. The titration-dose group achieved significantly higher median hemoglobin (9.9 g/dl) compared with the fixed-dose group (9.4 g/dl). The fixed-dose group had a significantly lower median cumulative dose of darbepoetin (median monthly dose of 30.9 µg) compared with the titration-dose group (53.6 µg median monthly dose). The FD and TD group received a median (Q1, Q3) cumulative dose per 4 weeks of darbepoetin of 30.9 (21.8, 40.0) µg and 53.6 (31.1, 89.9) µg, respectively; the median of the difference between treatment groups was −22.1 (95% CI, −26.1 to −18.1) µg.ConclusionsThese findings indicate no evidence of difference in incidence of red blood cell transfusion for a titration-dose strategy versus a fixed-dose strategy for darbepoetin. This suggests that a low fixed dose of darbepoetin may be used as an alternative to a dose-titration approach to minimize transfusions, with less cumulative dosing.

Pediatric subset of primary immunodeficiency patients treated with SCIG: post hoc analysis of SHIFT and IBIS pooled data

Background Primary immunodeficiencies (PID) constitute a heterogeneous group of more than 350 monogenetic diseases. PID patients with antibody impairment require lifelong administration of immunoglobulin G replacement therapy, administered either intravenously (IVIG) or subcutaneously (SCIG). Although the effectiveness of weekly and biweekly (every other week) SCIG administration has been shown in several trials, data on the viability of these two regimens in pediatric PID patients are sparse. Methods Data on the pediatric subsets of PID patients enrolled in SHIFT (weekly) and IBIS (biweekly) studies were pooled and analyzed to indirectly compare two different 20%-concentrated SCIG (Hizentra®) regimens. The primary endpoints were to evaluate trough IgG levels and cumulative monthly doses; the secondary endpoint was to analyze incidence of infections. Results Fifteen and 13 children from the SHIFT and IBIS studies were included, respectively. Cumulative 20%-concentrated SCIG monthly dose was slight lower for the biweekly regimen (Δ = − 2.04, 90% CI − 8.3 to 4.23). However, the trough IgG levels were similar between the two groups (Δ = 0.28, 90% CI − 0.51 to 1.07) and constantly above the threshold of 5 g/L. After adjusting for potential confounders, the annualized rate of infections was similar between SHIFT and IBIS patients (incidence rate ratio = 1.09, 90% CI 0.72–1.67); only 1 serious bacterial infection was experienced by a patient in the IBIS group. Conclusion In pediatric PID patients, weekly and biweekly Hizentra® administrations appeared equally effective treatment options.

Tocilizumab in a Case of Refractory Idiopathic Orbital Inflammation: 6-Year Follow-Up Outcomes

Idiopathic orbital inflammation (IOI) is a noninfectious inflammatory disease whose etiology remains unknown. Treatment is focused on reducing inflammation, which becomes challenging in nonresponding cases. We report the case of a 59-year-old woman with refractory IOI that showed a positive response to tocilizumab therapy. The patient was diagnosed with a unilateral sclerosing IOI for 9 years and showed a negative control with previous oral steroids, peribulbar steroid injections, radiotherapy, immunosuppressors, and intravenous rituximab. After the initiation of 8 mg/kg intravenous tocilizumab, a complete reduction of the pain and the orbital inflammation signs was observed and her condition remained stable for the following 6 years under a monthly dose of 4 mg/kg. In recalcitrant IOI cases, tocilizumab could be considered a possible treatment to reduce inflammatory signs and symptoms with positive long-term outcomes as in our case.

Association Between Male Use of Pain Medication and Fecundability

Administration of pain relievers has been associated with both lower and higher risks of adverse reproductive outcomes in animals. In the sole investigation of male pain-reliever use and human fertility carried out to date, Smarr et al. (Hum Reprod. 2016;31(9):2119–2127) found a 35% reduction in fecundability among males with urinary acetaminophen concentrations in the highest quartile (>73.5 ng/mL) versus the lowest (<5.4 ng/mL). We analyzed data from 1,956 males participating in Pregnancy Study Online, a preconception cohort study of North American couples enrolled between 2013 and 2019. Males and females completed baseline questionnaires on sociodemographic characteristics, lifestyle, medication use, and medical history; females completed bimonthly follow-up questionnaires for up to 12 months. We categorized pain medications by active ingredient (ibuprofen, acetaminophen, naproxen, aspirin) and cumulative monthly dose. We used proportional probabilities models to calculate fecundability ratios and 95% confidence intervals, adjusting for potential confounders. In the 4 weeks before baseline, 51.7% of males used pain medications. Adjusted fecundability ratios were 1.02 for ibuprofen (95% confidence interval (CI): 0.91, 1.13), 0.89 for acetaminophen (95% CI: 0.77, 1.03), 1.07 for naproxen (95% CI: 0.85, 1.35), and 1.05 for aspirin (95% CI: 0.81, 1.35), as compared with nonuse of each medication. In this study, male use of pain medications at low doses was not notably associated with fecundability.