Subcutaneous Self-injection Research Articles

Vitamin B12 deficiency

No international treatment standard for B12 deficiency exists. Current practice predominantly relies on more than 50 years old data. Consequently, this review investigates that we still recommend five injections with 1 mg B12 over 10 days followed by maintenance therapy with 1 mg oral B12 daily or injections, of which the interval is guided by symptom relief rather than normalization of biomarkers. Clinical studies are highly warranted and should include formulation and administration of B12. Subcutaneous self-injection may prove cost-effective and benefit an individualized treatment strategy.

Development and validation of an ultra-high performance liquid chromatography-tandem mass spectrometry method for quantifying lenacapavir plasma concentrations: Application to therapeutic monitoring

Although current antiretroviral therapy (ART) effectively suppresses HIV in the blood, regimens may fail due to suboptimal treatment history and non-adherence to ART. In these scenarios, accumulation of viral resistance mutations to ART drug classes may occur. For these treatment-experienced people living with HIV (PLWH), activity against resistant viral strains is required; lack of therapeutic efficacy will result in continued viral replication and progression to acquired immunodeficiency syndrome. New treatment options have emerged. Lenacapavir is a first-in-class long-acting HIV-1 capsid inhibitor approved for the treatment of HIV in treatment-experienced patients. Lenacapavir is approved with an initiation regimen of oral and subcutaneous injection dosing followed by subcutaneous self-injection every 6 months. With infrequent dosing, therapeutic drug monitoring may be necessary to ensure adequate concentrations are consistently achieved in the plasma to assure treatment adherence and prevent further HIV resistance formation. To this end, we developed and validated a highly selective ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to quantify lenacapavir concentrations in human plasma. A simple protein precipitation with acetonitrile followed by supernatant dilution was performed. Lenacapavir and its stable labeled internal standard were separated at 1.90 min using a multi-step UPLC gradient. The assay for lenacapavir quantification was extensively validated according to the United States Food and Drug Administration Bioanalytical Guidelines over a clinically relevant range of 0.1 to 500 ng/mL with excellent linearity (R2 ≥ 0.9960). This analytical method achieves acceptable performance of trueness (89.7–104.1 %), repeatability, and precision (CV < 15 %). We applied this method to quantify a clinical sample and to determine the percent protein-unbound. This method can be utilized for the therapeutic monitoring of lenacapavir in human plasma for monitoring HIV treatment efficacy.

Safe and Effective Subcutaneous Self-Injection of Bimekizumab with Safety Syringe and Auto-Injector Devices: Results from a Multicenter, Randomized, Open-Label Study in Patients with Psoriatic Arthritis.

Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, key drivers of chronic inflammation. Bimekizumab must be injected subcutaneously and so patients require self-injection options that meet their preferences. This study evaluated safe and effective self-injection of bimekizumab by patients with psoriatic arthritis using the 1 mL safety syringe (SSy) or the 1 mL auto-injector (AI). The DV0004 devices study (NCT04109976) was a sub-study of BE VITAL, a multicenter, open-label extension of BE OPTIMAL (NCT03895203) and BE COMPLETE (NCT03896581) in patients with active psoriatic arthritis. After receiving training, patients subcutaneously self-injected bimekizumab 160 mg at Baseline and Week 4. The primary and secondary endpoints were the proportion of patients self-injecting bimekizumab safely and effectively at Week 4 and Baseline, respectively. Patient self-injection experience was evaluated using the pain visual analog scale (VAS) and the Self-Injection Assessment Questionnaire (SIAQ). Overall, 214 patients were randomized 1:1 at Baseline. All evaluable patients safely and effectively self-injected bimekizumab at Week 4 (SSy: n=105; AI: n=104) and Baseline (SSy: n=106; AI: n=106). Mean pain VAS scores were generally low at Week 4 (SSy: 11.0; AI: 11.4) and Baseline (SSy: 9.5; AI: 14.9). High mean pre- and post-injection SIAQ scores (≥6.7) were observed for both devices indicating a positive overall patient experience with self-injection. Self-injection was well tolerated with no reports of treatment-emergent adverse device effects (TEADEs), serious TEADEs or discontinuations due to TEADEs. Four non-device-related injection site reactions during the sub-study were reported in the parent study; all were mild, did not lead to discontinuation and resolved without treatment. All devices maintained their structural and functional integrity post-use. All patients self-injected subcutaneous bimekizumab safely and effectively using either device at Baseline and Week 4. Overall, patients reported a positive self-injection experience.

Demographic, Physical, and Psychological Determinants of Patient Experience with Subcutaneous Self-Injection in Patients with Rheumatoid Arthritis: Structural Equation Modeling Approach.

To achieve a better patient experience with self-injection, an assessment of potential demographic, physical, and psychological barriers is necessary. The aim of this study was to examine the demographic, physical, and psychological characteristics associated with the experiences of self-injection in patients with rheumatoid arthritis (RA). In this study, overall patient experience with subcutaneous self-injection was assessed using the Self-Injection Assessment Questionnaire. Upper limb function was assessed using the three domains of the Health Assessment Questionnaire associated with upper extremity disability (dressing and grooming, eating, and grip). Structural equation modeling was used to estimate the association between the demographic and clinical characteristics of patients with RA and their experiences with self-injection in the theoretical model. Data from 83 patients with RA were analyzed. Compared with younger patients, elderly patients were more likely to experience lower self-confidence, self-image, and ease of use. Female patients had lower ease of use than male patients. In terms of upper limb function, patients with more difficulty in performing activities of daily living were more likely to have a lower self-image. Self-injection perceptions before learning the method of injection, such as fear of needles and anxiety about self-injection, were associated with post-injection feelings, injection site reactions, self-confidence, and ease of use. To optimize patients' experiences with self-injection, healthcare workers should assess each patient's age, sex, upper limb function, and pre-self-injection perceptions as demographic, physical, and psychological barriers.

#4033 RAPID COMPLEMENT INHIBITION WITH THE C5 INHIBITOR CROVALIMAB: A TIMING ANALYSIS USING ANIMAL MODEL AND COMPOSER TRIAL DATA

Abstract Background and Aims Atypical haemolytic uraemic syndrome (aHUS) is a life-threatening disease, characterised by acute kidney injury, thrombocytopenia, and microangiopathic haemolytic anaemia due to complement dysregulation. Currently approved treatments for aHUS include the anti-complement C5 monoclonal antibodies eculizumab and ravulizumab. Although currently approved therapeutic options are effective at both inhibiting complement-mediated thrombotic microangiopathy (TMA) and improving renal function, the regular intravenous (IV) infusion dosing regimens impose a significant treatment burden, particularly in paediatric patients (pts) with aHUS, who may need dialysis in the future due to chronic kidney injury and would benefit from preservation of vascular access. Crovalimab is a novel monoclonal antibody developed against complement C5, engineered to allow for small volume subcutaneous (SC) self-injection every 4 weeks, in a weight-based dosing regimen [1]. In the adaptive Phase I/II COMPOSER trial (NCT03157635) evaluating crovalimab in pts with paroxysmal nocturnal haemoglobinuria (PNH), that, like aHUS, is a complement disorder characterised by uncontrolled complement activation, crovalimab has shown maintained disease control and was well tolerated after a median exposure of 3 years. Further, a Phase III study evaluating crovalimab in previously untreated pts met its primary efficacy endpoints [2]. The efficacy and safety of crovalimab are currently being evaluated in adult and paediatric pts with aHUS, either treatment-naive or switching from another complement inhibitor, in the ongoing Phase III single-arm COMMUTE-a and COMMUTE-p trials [3]. Due to the rapidly progressing nature of aHUS, pts experiencing a TMA require rapid suppression of complement activation upon diagnosis to shut down the complement cascade and avoid further kidney deterioration and organ damage. Here, data from in vivo models and the COMPOSER trial were used to determine the time to complete complement inhibition after first crovalimab IV dose. Method Crovalimab's ability to suppress C5 function and complement activity rapidly was initially studied in in vivo models of cynomolgus monkeys. This study assessed the pharmacokinetics and pharmacodynamics of crovalimab in these monkeys after a single IV or SC dose. As part of this study, four animals per group were evaluated with single 4 mg/kg IV and 20 mg/kg IV doses. Crovalimab was also evaluated in the four-part, Phase I/II COMPOSER trial. Part 2 (n = 10) and Part 4A (n = 8) enrolled pts with PNH who were naive to complement inhibition. Pts in Part 2 received crovalimab 375 mg IV on Day 1, 500 mg IV on Day 8, 1000 mg IV on Day 22 and 170 mg SC weekly from Day 36 for 20 weeks. Pts in Part 4A received an optimised crovalimab dosing regimen of 1000 mg IV on Day 1, 340 mg SC on Days 2, 8, 15, and 22 and 680 mg SC Q4W from Day 29 onwards for 20 weeks. Crovalimab concentration, free C5 and complement activity were measured using validated assays in cynomolgus monkeys and in pts with PNH. Results Compared with baseline values in cynomolgus monkeys, a single crovalimab IV dose of 4 mg/kg reduced mean free C5 concentration by 99.6% and terminal complement activity by 81.4%, within 5 minutes after administration. In treatment-naive pts from COMPOSER Parts 2 and 4, mean free C5 concentration dropped to below 1 μg/mL, indicating a high level of target engagement within 1–6 hours from the first IV dose (Figure 1). Correspondingly, inhibition of terminal complement activity was reached within 1 hour, with values near or below the lower limit of quantification (10 U/mL; Figure 2). Complete complement blockade was generally maintained long-term, up to Week 20, in both Parts 2 and 4, regardless of dose. Conclusion Crovalimab induced a complete, rapid, and sustained blockade of terminal complement activity in both non-human primates and pts with PNH, within hours from first dose. The dosing schedule of crovalimab included an initial IV loading dose, allowing for a rapid onset of action, followed by a convenient long-term SC maintenance regimen.

5612539 TRIAL IN PROGRESS: THE RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 2A CROSSWALK-C TRIAL EVALUATING THE EFFICACY OF CROVALIMAB AS ADJUNCT TREATMENT IN THE PREVENTION OF VASO-OCCLUSIVE EPISODES (VOES) IN PATIENTS (PTS) WITH SICKLE CELL DISEASE (SCD)

Background: SCD is a group of autosomal recessive red blood cell (RBC) disorders caused by a single point mutation in the β-globin gene, with either homozygous inheritance or heterozygous co-inheritance with other pathogenic variants of the β-globin gene. Hemoglobin S, produced as a result of this point mutation, polymerizes within RBCs under certain conditions, distorting them and generating dense and sickle RBCs. These pathologic RBCs contribute to microvascular occlusions, which may present as acute painful episodes called VOEs. Pts with SCD may also have severe chronic anemia, chronic pain, immune dysfunction, and progressive multi-organ damage. Current therapies for SCD include hydroxyurea, as well as newer treatments such as L-glutamine, crizanlizumab, and voxelotor. Despite these treatments, considerable morbidity and mortality among pts with SCD represents a significant unmet medical need. Complement pathway activation has been reported in pts with SCD at baseline, in acute pain crises, and in delayed hemolytic transfusion reaction. Accumulating nonclinical data suggest the potential multimodal role for complement dysregulation in the pathophysiology of SCD, including vaso-occlusion, hemolysis, inflammation, thrombogenicity, endothelial activation, and end-organ damage.1 The complement pathway can be targeted with crovalimab, a novel anti-C5 monoclonal antibody that allows for small-volume subcutaneous (SC) self-injection. In a Phase 1/2 paroxysmal nocturnal hemoglobinuria (a complement-mediated disorder) study, crovalimab showed rapid and sustained complement inhibition with promising efficacy and safety.2 Aim: CROSSWALK-c (NCT05075824) is a randomized, double-blind, placebo-controlled, Phase 2a study evaluating the efficacy and safety of crovalimab as adjunct therapy in preventing VOEs in pts with SCD. Methods: Pts aged 12 to 55 years, weighing ≥40 kg, with a confirmed diagnosis of SCD, homozygous hemoglobin S (HbSS) or sickle cell β0 thalassemia (HbSβ0), and presenting with 2 to 10 VOEs are eligible, including pts on concurrent SCD-directed therapies. Vaccinations against Neisseria meningitidis, Haemophilus influenzae type B, and Streptococcus pneumoniae are required. Pts with a history of hematopoietic stem cell transplant will be excluded. Eligible pts will be randomized 1:1 to the crovalimab or placebo arms (Figure). An initial intravenous loading dose of crovalimab or placebo will be given on Week 1, Day 1, followed by SC dose on Week 1, Day 2, and then weekly SC doses on Weeks 2–4. Starting Week 5, a maintenance dose will be given every 4 weeks for 48 weeks. All study treatment will be given according to a weight-based tiered dosing schedule (pts weighing ≥ 40 kg to < 100 kg and pts ≥ 100 kg). The primary objective is to evaluate the efficacy of crovalimab vs placebo based on the annualized rate of medical facility VOEs. Key secondary efficacy objectives are the annualized rate of acute chest syndrome, the annualized rate of home VOE, and change in urinary albumin–creatinine ratio, tricuspid regurgitant jet velocity, and Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue score in adults, from baseline to Week 49. Safety, pharmacokinetic, immunogenicity, and exploratory biomarker objectives will also be evaluated. Protocol updates are in progress. Results: Primary results are expected in July 2024. Summary: CROSSWALK-c is enrolling pts with SCD and chronic VOEs in six countries.

Trial in Progress: The Randomized, Double-Blind, Placebo-Controlled Phase IIa CROSSWALK-c Trial Evaluating the Efficacy of Crovalimab As Adjunct Treatment in the Prevention of Vaso-Occlusive Episodes (VOEs) in Patients with Sickle Cell Disease (SCD)

BackgroundSCD is a group of autosomal recessive red blood cell (RBC) disorders caused by a single point mutation in the β- globin gene, with either homozygous inheritance, or heterozygous co-inheritance with other pathogenic variants of the β-globin gene. This point mutation results in the production of hemoglobin S, which polymerizes within RBCs under certain conditions, leading to the distortion of the RBC membrane and generation of dense and sickle RBCs. These pathologic RBCs contribute to microvascular occlusions in patients with SCD, which present as acute painful episodes called VOEs. In addition to VOEs, patients with SCD may experience severe chronic anemia, chronic pain, immune dysfunction, and progressive multi-organ damage. The current treatment strategy for patients with SCD includes hydroxyurea, along with newer treatments such as L-glutamine, crizanlizumab, and voxelotor. However, despite the availability of these treatments, considerable morbidity and mortality among patients with SCD represents a significant unmet medical need. Activation of the complement pathway has been described in patients with SCD at baseline, in acute pain crisis, and in delayed hemolytic transfusion reaction. Accumulating nonclinical data suggest the potential multimodal role for complement dysregulation in the pathophysiology of SCD, including vaso-occlusion, hemolysis, inflammation, thrombogenicity, endothelial activation, and end-organ damage (Roumenina et al. Am J Hematol 2020). Crovalimab is a novel anti-C5 monoclonal antibody that allows for small-volume subcutaneous (SC) self-injection. Crovalimab demonstrated rapid and sustained complement inhibition with promising efficacy and safety in a Phase I/II study (Röth et al. Blood 2020), in patients with paroxysmal nocturnal hemoglobinuria, a complement-mediated disorder.Study Design and MethodsCROSSWALK-c (NCT number pending) is a placebo-controlled, randomized, double-blind, Phase IIa study evaluating the efficacy and safety of crovalimab as adjunct therapy in preventing VOEs in patients with SCD. Patients aged ≥ 12 years to ≤ 55 years, weighing ≥ 40 kg, with a confirmed diagnosis of SCD, homozygous hemoglobin S (HbSS) or sickle cell β 0 thalassemia (HbSβ 0), and presenting with ≥ 2 to ≤ 10 VOEs are eligible for this study. Patients on concurrent SCD-directed therapies are also eligible. Vaccination against Neisseria meningitidis, Haemophilus influenzae type B, and Streptococcus pneumonia are required for enrollment. Patients with a history of hematopoietic stem cell transplant are excluded from the study. Eligible patients will be randomized 1:1 to the crovalimab or placebo treatment arms (Figure). An initial intravenous loading dose of crovalimab or placebo will be administered on Day 1 Week 1, followed by four weekly SC doses on Day 2 Week 1, and then on Weeks 2-4. Maintenance dosing will be administered from Week 5, followed by once every 4 weeks thereafter, for 48 weeks. All patients will receive study treatment according to a weight-based tiered dosing schedule. The primary objective is to evaluate the efficacy of crovalimab compared with placebo, based on the annualized rate of medical facility VOEs. Secondary efficacy objectives include the annualized rate of acute chest syndrome, the annualized rate of home VOE, and change in urinary albumin-creatinine ratio, tricuspid regurgitant jet velocity, and Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue score in adults, from baseline to Week 49. Safety, pharmacokinetics, immunogenicity, and exploratory biomarker objectives will also be evaluated. [Display omitted] DisclosuresCallaghan: Agios Pharmaceuticals: Current Employment; Roche/Genentech: Consultancy, Speakers Bureau; Global Blood Therapeutics: Consultancy, Speakers Bureau; Forma: Consultancy; Hema Biologics: Consultancy; Takeda: Consultancy, Speakers Bureau; Sanofi: Consultancy; BioMarin: Consultancy; Spark: Consultancy; uniQure: Consultancy; Chiesi: Consultancy; Kedrion: Consultancy; Pfizer: Consultancy. Ataga: Novartis: Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Consultancy; Forma Therapeutics: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Consultancy; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees. De Franceschi: F. Hoffmann-La Roche Ltd: Consultancy. Minniti: CSL Behring: Other: Endpoint adjudicator ; Forma: Consultancy; Novo Nordisk: Consultancy; Chiesi: Consultancy; Bluebird Bio: Other: Endpoint adjudicator ; Novartis: Consultancy; GBT: Consultancy; F. Hoffmann-La Roche Ltd: Consultancy. Balachandran: F. Hoffmann-La Roche Ltd: Current Employment. Imbs: F. Hoffmann-La Roche Ltd: Consultancy; Certara Inc.: Current Employment. Perretti: F. Hoffmann-La Roche Ltd: Current Employment. Ramos: Genentech, Inc.: Current Employment. Sostelly: F. Hoffmann-La Roche Ltd: Current Employment. Bartolucci: Bluebird: Consultancy, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees, Steering committee, Research Funding; Fabre Foundation: Research Funding; Jazz Pharma: Other: Lecture fees; AGIOS: Consultancy; INNOVHEM: Other: Co-founder; Emmaus: Consultancy; Addmedica: Consultancy, Other: Lecture fees, Research Funding; Hemanext: Consultancy; F. Hoffmann-La Roche Ltd: Consultancy; GBT: Consultancy.

P073 Interactive rheumatology biologic self-injection video advice using an SMS based video resource: successful implementation during a pandemic

Background/Aims The COVID-19 pandemic has resulted in a number of changes in practice in the UK, including the reduction in routine day-case attendances for intravenous rheumatology treatments. Due to redeployment and resultant staff shortages, we required alternatives to day case attendance. The usual face-to-face education that normally supports this was not possible. Methods In March 2020, we identified patients receiving monthly intravenous tocilizumab on our day-unit and planned a supported transition to weekly subcutaneous self-injection. We designed, planned, storyboarded, video-recorded, and piloted a 15-minute tocilizumab self-injection interactive video resource, using evidence-based educational methodology. This included: an introduction; explanation of the change and context; a one-minute video of our nurse specialist self-administering a sample injection; a close-up injection video; local logistical information and contact details, and a voluntary anonymous web-based evaluation. The interactive resource was searchable and contained links to supporting information, including a link to manufacturer patient education material. The intervention received rapid institution and pharmacy approval for distribution. We sent it via SMS message to our cohort of patients using a commercial partner (HealthComm UK) from 8.4.20, using an established method we have recently described. Simultaneously, we made it publicly available on our departmental website. We collated feedback and usage metrics over an eight-week period (8.4.20 - 3.6.20). Results We identified 69 patients eligible to switch to self-injection; all were sent the SMS link. Our resource was viewed by 39/69 patients (57%) via the unique SMS link, a total of 97 times (mean 2.5 views/patient). Others watched it on our website, 534 views, by 283 unique visitors (1.9 views/visitor). In total, 24/69 patients (35%) returned a complete evaluation of the video, 16/24 (67%) felt more confident injecting after watching the resource. Age ranges in deciles (number) was: 40-49, (5); 50-59, (6); 60-69, (8); >70, (5). Likert scores for satisfaction with the resource (1=strongly disagree; 5=strongly agree) were as follows: video ease and playback (4.1); improved confidence of self-injection (4.0), usefulness of SMS methodology (4.3), usefulness of interactive resource over video (3.7). A number (9/24, 38%) had never self-injected any medicine. Most completing the evaluation (18/24, 75%) viewed the resource on mobile phones. Written feedback, where given, was positive in 18/19 (95%) cases, one patient identified they could not watch the video. Conclusion The COVID-19 pandemic has increased the use of telerheumatology resources. We have demonstrated that interactive video resources are a rapid, acceptable, and useful method of delivering rheumatology education. This intervention is low cost (£0.01 per SMS) and we used existing e-learning technology already licensed to our hospital at no additional cost to the department, other than staff time. Our findings have implications for other aspects of rheumatology self-care and we call for further research in this area. Disclosure P. Mistry: None. J. Bateman: None. K. Hughes: None.

A Companion App to Support Rheumatology Patients Treated with Certolizumab Pegol: Results From a Usability Study.

BackgroundCertolizumab pegol (CZP) is an anti-tumor necrosis factor drug approved for the treatment of multiple moderate to severe chronic inflammatory diseases. In the European Union, CZP is approved for administration by subcutaneous self-injection using a prefilled syringe, prefilled pen, or reusable electromechanical auto-injector (electronic device). CimplyMe is a companion app for use alongside CZP self-injection devices, designed to support CZP-treated patients self-managing their treatment and disease.ObjectiveThis study aimed to validate the usability of the companion app by demonstrating that tasks required for use can be performed successfully by intended end users.MethodsWe recruited 15 patients with moderate to severe rheumatoid arthritis, currently prescribed biologic treatment, and using apps on a smart phone. Patients were assessed on their ability to use the companion app in a setting designed to simulate a location where patients regularly administer biologic treatment. To assess the usability of the key features of the app, 8 critical and 3 noncritical tasks were designed. Patients’ success on each task was recorded through observations or knowledge-based questions. Successes with difficulty and use errors were also recorded. If a patient made a use error at the first attempt, a second attempt was allowed. Second-attempt use errors were recorded as a task failure.ResultsA total of 207 first attempts at the 14 components of the 8 critical tasks were evaluated (3 patients failed to complete one component); 178 (86.0%) critical tasks were successfully completed at the first attempt. The remaining first attempts comprised 16 (7.7%) successes with difficulty and 13 (6.3%) use errors, which had to be repeated. One critical task was not re-attempted by one patient due to time constraints; however, there were no use errors in the 12 completed second attempts. A total of 107 first attempts at the 3 noncritical tasks were made, all of which (107/107, 100.0%) were completed without use errors.ConclusionsIn simulated testing, patients were able to successfully use the companion app without formal training. This study suggests the companion app is easy to use and could help patients prescribed CZP better manage their treatment and disease.

Patient Satisfaction with the Etanercept Biosimilar SB4 Device, Among Rheumatoid Arthritis and Spondyloarthropathy Patients - A German Observational Study

Background: The etanercept biosimilar SB4 is a TNF inhibitor authorised for use as a targeted Biological Disease-Modifying Anti-Rheumatic Drug (bDMARD). Various administration devices have been developed for subcutaneous self-injection of bDMARDs. Objective: This study surveyed patient satisfaction with their experience of using the SB4 pre-filled pen device. Methods: This non-interventional, cross-sectional, multi-centre study enrolled adult rheumatoid arthritis and spondyloarthropathy patients who had been treated for at least three months with the SB4 pre-filled pen. Based on a standardized questionnaire, patients rated general satisfaction, handling, user-friendliness, physical characteristics, and training material received. A total of 492 eligible patients completed questionnaires at 43 centres across Germany between August 2017 and June 2018. Data were analysed descriptively. Pre-defined subgroup analyses by previous therapy and by indication were performed. Results: Overall, 87% (95% CI 83% - 90%) of patients reported being ‘satisfied’ or ‘very satisfied’ with the pen. 89% of patients reported that the pen was ‘simple’ or ‘very simple’ to use. Most patients (87%) self-injected. 93% of patients who received training on the use of the pen were ‘satisfied’ or ‘very satisfied’ with the training provided. In this cross-sectional study, 12 patients reported an Adverse Event (AE) and one patient reported a treatment-related AE (nausea). Conclusion: The results demonstrated a high level of general satisfaction among patients using the SB4 pre-filled pen as well as satisfaction with ease of use for patients who were either naïve to bDMARDs or who had switched to SB4 from other bDMARDs.

Subcutaneous Self-Injection Therapy of Heparin for a Case of Ebstein Disease with Artificial Valve and Warfarin-Induced Skin Ulcer

Subcutaneous Self-Injection Therapy of Heparin for a Case of Ebstein Disease with Artificial Valve and Warfarin-Induced Skin Ulcer

Correct performance of subcutaneous injections in plaque psoriasis: comparison of trained and untrained patients with different application systems in routine clinical care

Background Moderate-to-severe plaque psoriasis can be treated very successfully with systemic therapies. Often the therapeutics must be injected subcutaneously. This prospective observational study aimed to compare the correct preparation and performance of subcutaneous injections in trained and untrained patients with plaque psoriasis. Materials and Methods We asked 110 patients (29.1% women, 70.9% men, injection system: 75.5% prefilled syringe, 24.5% autoinjector) to what extent they were trained for self-injection. While participants injected a sham injection with their current system, we evaluated the preparation, execution, and follow-up using a newly developed scoring system. Results 87.3% (n = 96) of the participants declared that they had been trained for self-injection. No statistically significant difference was observed between the trained and untrained participants in performing the injection correctly (p = .458). The most common mistakes were the wrong preparation and follow-up of the injection. A bifactorial rank-variance analysis showed a negative influence of the factor injection system (prefilled syringe) on the total score (p = .005). Conclusion We can indicate that patients with plaque psoriasis are well prepared for subcutaneous self-injection. Self-injection of systemic therapies is easy to perform, especially with patient-friendly systems, and does not require specialized training.

Injectable contraception: emerging evidence on subcutaneous self-administration.

Injectable contraception is a widely available and popular family planning method globally. It has evolved to allow for subcutaneous self-injection (DMPA-SC, Depo medroxyprogesterone acetate-subcutaneous). In this review, we will focus on research evaluating DMPA-SC, with specific regard to continuation rates, safety, and satisfaction among users. Emerging evidence from the United States, Malawi, Uganda, and Senegal has established safety and higher continuation rates among self-inject users, compared with provider-inject users. Continuation is 10-28% higher among DMPA-SC self-inject users. Self-inject users across studies were highly satisfied and reported DMPA-SC was easy to use. Studies indicate continuation is likely to be attributable to self-administration and user autonomy, rather than inherent properties of the DMPA-SC injection. DMPA-SC should be made available in high-resource and low-resource settings. Future efforts should be focused on implementation and evaluating how to best add DMPA-SC to the method mix. Cost-benefit analyses will need to evaluate the up-front costs of DMPA-SC for clients, facilities, and health systems compared with the higher continuation rates and saved opportunity-costs over time. Task-shifting strategies and development of mobile phone technologies to assist users in adherence should be considered in future service scale-up.

A Study to Evaluate the Safe and Effective Use of the Prefilled Safety Syringe or the Auto-injector for the Subcutaneous Self-injection of Bimekizumab Solution by Subjects With Active Psoriatic Arthritis

A Study to Evaluate the Safe and Effective Use of the Prefilled Safety Syringe or the Auto-injector for the Subcutaneous Self-injection of Bimekizumab Solution by Subjects With Active Psoriatic Arthritis - Full Text View.

Smart Microneedle Fabricated with Silk Fibroin Combined Semi-interpenetrating Network Hydrogel for Glucose-Responsive Insulin Delivery.

Microneedle (MN) technology, which can transdermally deliver insulin in a noninvasive manner, offers a promising way to replace subcutaneous self-injection for diabetes management. Hydrogel is an attractive candidate for MN fabrication because of its biocompatibility, controllable degradability, and possibility to achieve sustained as well as stimuli-responsive drug delivery. Herein, we report a smart MN composed of a semi-interpenetrating network (semi-IPN) hydrogel prepared by biocompatible silk fibroin (SF) and phenylboronic acid/acrylamide for glucose-responsive insulin delivery. Six fabrication methods were investigated to maintain the glucose sensitivity of the hydrogel while avoiding deformation during fabrication. The optimized method was to fabricate smart MNs using a two-layer strategy, with a needle region formed by the SF combined semi-IPN hydrogel and the base layer fabricated by SF. The hybrid MN autonomously released insulin well-correspondent to the glucose change pattern via the regulation of the skin layer formed on the surface. Furthermore, this hybrid MN retained its original needle shape after 1 week in aqueous system, thus eliminating the safety concerns associated with dissolving MNs and suggesting the possibility for sustained delivery. This nondegradable smart MN is promising to provide on-demand insulin in a long-acting, painless, and convenient way.

A multicenter, randomized, rater-blinded, parallel-group, phase 3 study to compare the efficacy, safety, and immunogenicity of biosimilar RGB-10 and reference once-daily teriparatide in patients with osteoporosis

SummaryThe efficacy and safety of RGB-10 and reference teriparatide were evaluated in a randomized 52-week study in 250 patients with osteoporosis at high risk of fracture. RGB-10 was equivalent to reference teriparatide in efficacy and had a comparable safety profile.IntroductionRGB-10 is the first biosimilar teriparatide authorized in the European Union. This multicenter, randomized, rater-blinded, parallel-group phase 3 study evaluated equivalence in efficacy and compared safety between RGB-10 and reference teriparatide in patients with osteoporosis at high risk of fracture for registration in Japan.MethodsAmbulatory postmenopausal women and men (≥ 55 years of age) with osteoporosis at high risk of fracture were randomized 1:1 to receive either RGB-10 or reference teriparatide 20 μg once daily via subcutaneous self-injection for 52 weeks. The primary efficacy endpoint was the percent change from baseline to 52 weeks in lumbar spine (L2–L4) bone mineral density (BMD). Safety outcomes and immunogenicity were also assessed.ResultsIn total, 250 patients (125 in each group) were randomized. The percent change from baseline to 52 weeks in lumbar spine (L2–L4) BMD (mean ± standard deviation) was 8.94% ± 6.19% in the RGB-10 group and 9.65% ± 6.22% in the reference teriparatide group. The estimated between-group difference (95% confidence interval) was − 0.65% (− 2.17% to − 0.87%) within the pre-specified equivalence margin (± 2.8%), which indicates equivalence in efficacy between the two groups. Changes in BMD at lumbar spine (L1–L4), femoral neck, and total hip and serum procollagen type I amino-terminal propeptide were also similar between the groups. Safety profiles, including immunogenicity, were comparable.ConclusionsThe therapeutic equivalence of RGB-10 to reference teriparatide was demonstrated. RGB-10 had comparable safety profile to that of reference teriparatide.

Exenatide extended-release pre-filled pen (Bydureon® BCise®): a profile of its use

The Bydureon® BCise® pre-filled pen was developed largely to simplify self-administration of exenatide extended-release for patients with type 2 diabetes, being comfortable and intuitive to use, with easy-to-mix medication, sterile and safe needle containment, reliable/accurate dose delivery, and indicators of complete dose delivery and device use. Subcutaneous self-injection with Bydureon BCise involves three simple key steps (mixing, unlocking and pressing against the skin to inject) and has a needle that remains hidden, ensuring sterility and reducing the likelihood of accidental injury. In a single-injection study, the Bydureon BCise pre-filled pen was largely considered ‘easy’/‘very easy’ to use, and had a high rate of successful injection completion, including among lay users with dexterity or visual impairment. As an add-on to diet and exercise or oral glucose-lowering therapy, Bydureon BCise once weekly improved glycaemic control and provided glycaemic benefits over subcutaneous twice-daily exenatide and oral once-daily sitagliptin. Bydureon BCise was also generally well tolerated and appeared to have a better gastrointestinal profile, but more injection-site reactions, than twice-daily exenatide, and a less favourable gastrointestinal profile, but greater patient satisfaction, than sitagliptin.

Patients', physicians', nurses', and pharmacists' preferences on the characteristics of biologic agents used in the treatment of rheumatic diseases.

ObjectiveTo estimate preferences in relevant treatment characteristics evaluated by different groups involved in the management of patients with rheumatic diseases.Subjects and methodsWe surveyed patients with rheumatic diseases, and rheumatologists, nurses, and pharmacists with experience in treatment with/provision of biologic drugs for these patients. Through a discrete choice experiment, participants evaluated 16 possible scenarios in which pairs of similarly efficacious treatments were described with six characteristics: 1) frequency of administration; 2) mode and place of administration; 3) manner, helpfulness, efficiency, and courtesy of health personnel; 4) frequency of reactions at the site of drug administration; 5) severity of generalized undesired/allergic reactions; and 6) additional cost. The direction and strength of preferences toward each characteristic level and the relative importance of each characteristic were estimated through a random-effects conditional logistic regression model.ResultsIn total, 513 patients, 110 rheumatologists, 51 nurses, and 46 pharmacists from 30 centers in Italy participated. Characteristics 3, 4, and 6 were the most important for every subgroup; 1 was least important for patients and rheumatologists, 2 was least important for pharmacists, and 2 and 5 were least important for nurses. For characteristic 2, pharmacists preferred subcutaneous self-injection with a syringe; nurses preferred assisted infusion at an infusion center close to the patient’s home; patients and rheumatologists preferred subcutaneous self-injection with a pen.ConclusionThe different preferences for some characteristics shown by the different groups can play an important role, together with purely clinical aspects, in the choice and consequent benefit of treatments, contributing also to a more satisfactory use of resources.

Ensuring continuity of care for patients transitioning from intravenous to subcutaneous therapy at a health system owned specialty pharmacy

Background: On 26 September 2016, the FDA approved ustekinumab for the treatment of Crohn’s disease, which uniquely requires administration via two distinctly different methods, induction intravenous infusion followed by maintenance of subcutaneous self-injection. While therapeutically appropriate, the two dosing methods present administrative challenges beyond currently available treatments including verification of insurance coverage for both medical and pharmacy benefit, coordination of medication distribution, and care coordination and communication between the infusion service and specialty pharmacy. To ensure continuity of care, the successful facilitation of this process requires a care system that has experience in managing both infusion and specialty pharmacy medications.Objectives: Describe process and key learnings for complex therapy administration.Methods: In this descriptive analysis we characterize the patient, provider, and dispensing process across multiple sites of care. We highlight common scenarios experienced by patients and summarize unique challenges of coordinating treatment across multiple care settings.Results: Prior to the approval of ustekinumab, Fairview Pharmacy Services identified potential gaps in coordination between different the clinical settings and partnered with the health system, local clinics, and infusion centers to seamlessly coordinate care across medication delivery settings. A designated Specialty Care Coordinator is responsible for performing end-to-end communication and coordination of all activities for patients to ensure the transition between delivery settings does not result in gaps in therapy. Since process implementation, Fairview has successfully coordinated ustekinumab administration for over 200 patients within and external to our health system to ensure all patients received the intravenous induction dose prior to receiving the subcutaneous maintenance dose. In addition, we identified scenarios where lack of coordination can result in disruption to treatment for the patient or medication waste to the healthcare system.Conclusions: Health system owned specialty and infusion pharmacy services are uniquely positioned to facilitate and coordinate a successful transition of complex therapy with minimal disruption across various clinical settings. Fairview Pharmacy Services unique care model and partnerships are equipped to handle both our own patients and those being seen outside the system.

Mitral valve nonbacterial thrombotic endocarditis: a rare multi-surgery-tolerant survivor of Trousseau\u2019s syndrome

BackgroundFew previous reports have documented cases of nonbacterial thrombotic endocarditis associated with Trousseau’s syndrome for which surgery proved possible for both the primary tumor and the cardiac lesion. The effectiveness of direct oral anticoagulants in patients with Trousseau’s syndrome has also received scant attention.Case presentationA 69-year-old man with repeated episodes of cerebral infarction was diagnosed as having nonbacterial thrombotic endocarditis after mitral valve replacement surgery. Stroke recurred preoperatively under apixaban administration. A stomach biopsy also identified gastric adenocarcinoma, and gastric surgery was performed on the 40th postoperative day. The patient was discharged from the hospital and has been free of thromboembolism under a regime of subcutaneous heparin self-injection thereafter.ConclusionsWe have reported a rare multi-surgery-tolerant survivor of Trousseau’s syndrome in whom subcutaneous heparin injection was useful for preventing thromboembolic events over a long period.