Subcutaneous Biological Therapy Research Articles

Switching from Intravenous to Subcutaneous Biological Therapy for Inflammatory Bowel Disease Patients Remains a Challenge.

Biological inflammatory bowel disease (IBD) medications, once limited to intravenous (IV) administration, can now be administered both via IV and subcutaneously (SC). This study investigates patient preferences, willingness to switch from IV to SC, and associated factors. A questionnaire covering demographics, disease-related inquiries, quality of life, and IBD medication preferences was distributed via email, the Israeli Crohn's Disease and Ulcerative Colitis Foundation, infusion centers, and clinics. From 454 IBD patients (median age: 42 years; 55.7% female), responses revealed a preference for SC every 8 weeks, which is comparable to daily oral dosing. Both options were significantly favored over IV every 8 weeks and SC every 2 weeks, with no statistically significant differences between the latter two. However, among patients who were experienced with both SC and IV administration, a clear preference for SC administration every 2 weeks over IV every 8 weeks surfaced. Among IV-treated patients, 54.5% resisted switching to SC. Key reasons for this included medical staff presence (57.7%), a fear of needles (46.4%), belief in infusion efficacy (37.1%), and longer intervals between infusions (36.1%). Findings suggest that transitioning from IV to SC treatment is challenging due to patient resistance, which is influenced by specific factors. Identifying and addressing these obstacles is crucial for optimizing IBD management.

Enabling faster subcutaneous delivery of larger volume, high viscosity fluids

ABSTRACT Objectives Many current subcutaneous (SC) biologic therapies may require >1 mL volume or have increased viscosity, necessitating new delivery system approaches. This study evaluated 2-mL large-volume autoinjector (LVAI) delivery performance across varying solution viscosities and design inputs to assess the design space and identify configurations that produce practical injection times. Methods Investigational LVAI delivery duration and volume, depot location, and tissue effects were examined in both air and in vivo models across various pre-filled syringe (PFS) cannula types (27 G Ultra-thin wall [UTW], 27 G special thin wall [STW], or 29 G thin-wall [TW]), drive spring forces (SFLOW or SFHIGH), and Newtonian solutions (2.3–50 centipoise [cP]). Results Within each design configuration, increasing PFS internal diameters and spring forces reduced delivery times, while increasing viscosity increased times. The 27 G UTW PFS/SFHIGH combination achieved shorter delivery times across all injection conditions, with 2 mL in vivo durations <15 seconds at ≤31 cP and routinely <20 seconds at 39 and 51 cP, with nominal and transitory tissue effects. Conclusion PFS cannula and spring force combinations can be tailored to achieve various injection durations across viscosities, while UTW PFS enables faster rates to potentially better accommodate human factors during LVAI injection, especially at high viscosity.

Adherence to subcutaneous biologic treatment for inflammatory bowel disease

BackgroundNonadherence to medication is common in patients with inflammatory bowel disease (IBD) and can result in disease complications, therapy escalation, and the need for corticosteroids. The aim of this study was to assess the adherence to self-administered subcutaneous biologic medications prescribed for IBD and to identify the risk factors for nonadherence. MethodsA retrospective cohort study on IBD patients initiated on subcutaneous biologic therapy between January 2016 and July 2019 was performed. Medical records were retrospectively reviewed for collection of demographic and IBD data. Medication possession ratios (mMPRs) during the first 12 months of treatment and at the end of the follow-up period (global, 42 months) were calculated. Nonadherence was defined as an mMPR of <90%. Multiple regression analysis was performed to assess the risk factors for nonadherence to therapy. ResultsA total of 154 patients (84 male and 70 female; mean age at biologic treatment initiation, 36±14 years; Crohn's disease, n=118; ulcerative colitis, n=31; indeterminate colitis, n=5) were included; 121 received adalimumab (ADA) and 33 received ustekinumab (UST); 63% were naive to anti-TNF therapy, while 16.9% previously received more than two biologic treatments. Mean time from IBD diagnosis to subcutaneous biological agent use was 16±10 months. Mean duration of subcutaneous agent use was 17.6 (SD, 11.0) and 17.08 (SD, 6.8) months for ADA and UST, respectively. Global nonadherence (mMPR≤90%) rate was 6.6% for all patients receiving subcutaneous treatment, 6.3% for ADA, and 6.5% for UST. Nonadherence during the first 12 months of treatment (n=98) was 6.1% for all patients, 2.7% for ADA, and 16% for UST. In the multivariate analysis, UST use was independently associated with higher nonadherence only within the first 12 months (OR, 6.7; 95% CI, 1.1–39.5). ConclusionsHigh global adherence to self-administered subcutaneous biologic treatment was shown in our study, with higher rates of adherence to ADA than to UST within the first 12 months.

P379 Variations in disease monitoring between Inflammatory Bowel Disease patients on intravenous and subcutaneous biologic agents

BackgroundThe availability of subcutaneous (SC) administration devices of biologics in addition to intravenous (IV) administration has influenced patients’ and clinicians’ preferences towards initiating or transitioning to SC administration particularly during the COVID-19 pandemic. Whilst SC administration improves patient convenience and reduces demands on infusion centres we hypothesised that the reduction in healthcare contact associated with SC therapies may reduce the opportunities available for objective disease assessment. We aimed to compare the uptake of objective assessment of disease activity between patients receiving IV and SC biologic therapy.MethodsPatients on maintenance infusion-based or subcutaneous biologic therapy for IBD between 09/2020 and 02/2021 were identified from a prospectively maintained database at an Australian tertiary IBD centre. Patients scheduled for review in IBD clinic for a prescription of maintenance biologic therapy during the follow-up period were included. Clinic records were reviewed to determine whether patients had undergone objective disease assessment including: biochemical investigation (C-Reactive protein) and Faecal Calprotectin (FCP) within the preceding 8 weeks and/or endoscopic/imaging assessment within the preceding 6 months of clinic review. Frequency of objective disease assessment was compared between patients who received IV versus SC maintenance biologic therapy.ResultsA total of 307 patients were included: IV maintenance n=195 (Infliximab n=135; Vedolizumab n= 60) and SC maintenance n=112 (Adalimumab n=54; Ustekinumab n=54; Golimumab n=4). Patients who received IV biologics were more likely than the SC cohort to have had biochemical assessment in the form of CRP (90% vs 72%, p<0.001) and FCP (54% vs 46%, p=0.16). Patients in the SC biologic cohort were more likely not to have had investigations completed prior to their clinical review (20% versus 4%, p<0.001). There was no difference in the overall rates of complete objective disease assessment (CRP/FCP and endoscopy/imaging) between the IV and SC cohort (28% vs 30% (p=0.74).ConclusionPatients on subcutaneous biologic therapies in our cohort were less likely to have had objective disease monitoring than those receiving intravenous biologics prior to scheduled IBD clinic review. Route of of biologic administration may influence rates of uptake of objective disease activity assessment. Tools that safeguard against the disparity of monitoring uptake, including messaging prompts and patient-centric mobile applications may help standardise the approach to objective disease assessment independent of the route of biologic administration.

Adherence to and patient's knowledge of self-management of subcutaneous biologic therapy in chronic inflammatory rheumatic diseases: results of a multicentre cross-sectional study.

Non-adherence to biologic therapy is an issue in chronic inflammatory rheumatic diseases (CIRDs) and might be related to poor patient knowledge of the risk of these therapies. Our aim here was to evaluate the level of patient adherence to and knowledge of self-care safety skills for biologic therapy. This was a multicentre, cross-sectional study in which out-patients visited an office- or hospital-based rheumatologist. All the patients received subcutaneous biologic therapy for CIRDs. We collected data on: 1. the level of CIRD patient adherence to current subcutaneous biologic therapy using both the self-administered Compliance Questionnaire Rheumatology 5 items (CQR5) and a simple adherence question; 2. patients' knowledge of self-management of biologic therapy by the self-administered BIOSECURE questionnaire; 3. sources of information related to biologic therapy. In all, 285 patients (rheumatoid arthritis, n=103; spondyloarthritis, n=153; psoriatic arthritis, n=25) were enrolled by 19 rheumatologists. The mean (SD) biologic therapy duration was 5.9 (4.9) years. Adherence to the current biologic therapy was high (79.3% and 57.5% according to the CQR5 questionnaire and the adherence question, respectively). Level of knowledge of self-care safety skills (median BIOSECURE score 71) was in the acceptable range. Level of adherence and level of knowledge of self-care safety skills for biologic therapy were not associated. Patients declared that the main sources of information were their rheumatologist (92.6%) and the rheumatology team (30.5%). According to the patients' estimation, adherence to biologic therapy and the level of knowledge of self-care safety skills related to biologic therapy are acceptable, and these domains are not related (e.g. level of adherence and level of knowledge of risks).

P669 Adherence to self-administered biologic therapies in inflammatory bowel disease: Experience in a tertiary hospital

Abstract Background Nonadherence to medications is common in patients with inflammatory bowel disease (IBD) and can result in disease complications, therapy escalation, and the need for corticosteroids. The aim of this study was to assess adherence to self-administered (subcutaneous) biologic medications prescribed for IBD and to identify risk factors for biologic nonadherence. Methods A retrospective cohort study was performed on IBD patients starting and receiving subcutaneous biologic therapies from January 2016 to July 2019. Medical records were retrospectively reviewed and demographic and IBD data were collected. A modified medication possession ratio (mMPR) was calculated for the first 12-month treatment and at the end of follow-up (global-42 months). Nonadherence was defined as mMPR of less than 90%. Multiple regression analysis was performed to assess risk factors associated with non-adherence therapy Results A total of 154 patients (84M/70F; mean age starting biologic treatment 36 ±14 years; Crohn’s disease n = 118/ ulcerative colitis n = 31/ indeterminate colitis n = 5) were included; 121 received Adalimumab (ADA) and 33 were on Ustekinumab (UST); 63% of patients were naive to anti-TNF and 16.9% had received &amp;gt;2 previous biological treatment. Mean time from IBD diagnosis to use of subcutaneous biological agent was 16 ± 10 months. Mean time of subcutaneous agents use was 17.6(SD11.0) and 17.08 (SD6.8)months for ADA and UST, respectively. Global nonadherence (n = 154) (≤90% mMPR) was 6.6% for all patients receiving subcutaneous treatment and 6.3% for ADA and 6.5% for UST. Nonadherence during first 12-month treatment (n = 98) was 6.1% for all patients and 2.7 % for ADA and 16% for UST, respectively. In the multivariate analysis, Ustekinumab use was independently associated with higher nonadherence only for first 12-months adherence (OR 6.7, 95% CI 1.1–39.5). Conclusion Self-administered biologic treatment showed adequate global adherence in our study. Using subcutaneous administration for biologic agents in IBD patients forces us to monitor and control their adherence to ensure the therapeutic benefit.

PBI8 UNKNOWN

As price pressure increases in crowded therapy areas, particularly with the increase in development of biosimilars, healthcare systems are becoming increasingly reliant on the introduction of generics to reduce spending. In this research, we test if physician price awareness and sensitivity for comparable treatments is sufficient to drive cost reductions alone, or if payer-led controls and guidelines must be implemented to effect this change. Quantitative surveys with conjoint analysis were performed using a sample of 256 EU5 physicians. A patient conjoint is a powerful statistical technique to probe the value physicians place on drug features in prescribing decisions. Physicians were instructed to allocate patients to treatment scenarios based on a number of coverage and economic attributes. Analysis was then performed to probe how changing the price of a new oral treatment impacted preference share relative to more established intravenous and subcutaneous biologic therapies. Self-assessed ratings of price awareness and “interest” (impact of price on prescribing decisions) were comparatively analysed with the conjoint price sensitivity output to identify potential correlations. Through the conjoint exercise, physicians exhibited little price sensitivity, irrespective of how they rated their own price awareness. Significant reductions in the price of the oral drug was not associated with similarly significant increases in preference share. Even when discounted to biosimilars, preference was not shifted away from the established biologics, and most movement in share was within classes rather than between classes. There was very poor correlation between self-assessed price “interest” and analytically derived price sensitivity. Despite concern over the cost of treatment, physicians show limited awareness and sensitivity to the actual cost associated with treatment. For the potential saving of biosimilars and lower cost alternatives to be realised, relying on physicians’ price sensitivity will not be sufficient, and strict payer management will also be necessary to drive this change.

Adherence to biologic therapy – Does it vary with ethnicity?

BackgroundPoor adherence to therapy remains a significant barrier to improving clinical outcomes in rheumatic diseases and carries a major financial burden. It has been linked to medication related patient beliefs, which were reported to differ between ethnic groups. Little is known about these variations in biologic therapies cohorts. The purpose of this study was to identify potential determinants of adherence to biologic drugs including an assessment of the influence of beliefs about medicines and compare determinants of adherence between patients of Caucasian versus other ethnicities (OE). Relationship of adherence to disease outcome was further explored.MethodsA prospective survey was undertaken of patients with inflammatory arthritis prescribed self-administered subcutaneous biologic therapies at our centre. Data were collected using a) self reported adherence b) five item compliance questionnaire for Rheumatology (CQR5) and c) Beliefs about Medications questionnaire (BMQ) specific-five items each for necessity and concern scales. The replies were assessed against the disease activity score measured on the day of recruitment to the survey.Results80 patients contributed to the survey. 90% were prescribed TNF inhibitors. 40 patients were of Caucasian origin and 40 belonged to OE-predominantly of South Asian descent (85%). Disease activity score (DAS) was significantly higher in OE patients with 3.7 (standard deviation (SD) 1.3) compared to Caucasian patients with a DAS of 2.9 (1.6) (p = 0.031). Negative beliefs (i.e. higher concern scale scores) about therapy were significantly more prevalent (24/40) (60%) in the OE group compared to the Caucasian cohort (14/40 (35%) (p = 0.043). 17/40 (42.5%) of OE patients were poorly adherent to biologic therapy compared to 12/40 (30%) of Caucasian participants (p = 0.308). Most respondents (68/80, 85%) agreed that their biologic therapies were necessary for their health. Amongst 12/80 (15%) who disagreed, only two were in the non-adherent group.ConclusionTo our knowledge, this is the first study to demonstrate ethnic differences in disease activity score and related negative beliefs regarding subcutaneous biologic therapies in people with rheumatic diseases.

Adherence to Anti-Tumor Necrosis Factor Therapy Administered Subcutaneously and Associated Factors in Patients With Rheumatoid Arthritis.

Adherence to biologic therapy is relatively poorly studied in rheumatoid arthritis (RA) because many of the studies have investigated the drug persistence, which represents only a surrogate of adherence. The aims of this study were to determine the extent of adherence in RA patients with subcutaneously administered anti-tumor necrosis factor methotrexate agents and to identify the risk factors for nonadherence. A cohort of RA patients who started a subcutaneous anti-tumor necrosis factor treatment were enrolled. After 12 months of treatment, all patients completed the 4-item Morisky Medication Adherence Scale questionnaire. Associations between beliefs and nonadherence and the influence of demographic, clinical, and radiographic features were assessed using logistic regression model. A total of 209 (80.4%) of the 260 patients were included in the analyses. Forty-three of 209 patients were considered nonadherent to their medication (20.6%) according to the 4-item Morisky Medication Adherence Scale. More than half (53.1%) of patients showed at least 1 form of nonadherent behavior.The logistic model showed that low disease activity (P = 0.003), higher patient-physician discordance ratings (P = 0.012), older age (P = 0.041), and a high number of comorbid conditions (P = 0.011) were significantly associated with increased likelihood of nonadherence. The overall nonadherence with subcutaneous biologic therapy is relatively high among RA patients and should be taken into account when a patient's response to treatment is unsatisfactory.

Treatment persistence among patients with rheumatoid disease (RA, AS, PsA) treated with subcutaneous biologics in Germany.

Patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) are frequently treated with subcutaneous biologic therapies when disease progresses or when response to synthetic disease-modifying antirheumatic drugs (DMARDs) is inadequate. This study analyzed treatment persistence and treatment patterns for RA, AS, and PsA patients in Germany initiating subcutaneous biologic therapies with and without prior DMARDs use. A retrospective cohort study was conducted using the Electronic Medical Record database of IMS Disease Analyzer, Germany. Patients who were ≥18 years old; had at least one ICD-10 diagnosis code of RA, AS, or PsA during the study period; and had exposure to a subcutaneous biologic agent between January 1, 2009 and June 30, 2012 were selected. Patients were required to have continuous observation ≥12 months prior to and after index medication date. Persistence was defined as consecutive days from treatment initiation until treatment discontinuation (≥60-day lapse in medication coverage). Patients were stratified by pre-index use of DMARDs. Kaplan-Meier analysis was conducted to assess time to discontinuation, and logistic regression was conducted to identify characteristics associated with persistence. A total of 576 RA, 108 AS, and 197 PsA patients without biologic experience during the pre-index period were selected. The percentages of RA, AS, and PsA patients persistent ≥12 months were 51.9, 48.1, and 57.9 %, respectively. Median persistent time over 12 months was 365.0 days for RA (mean 245.9 days), 281.0 for AS (mean 228.5), and 365.0 for PsA (mean 264.1). In the RA cohort, a significantly higher proportion of those with pre-index DMARD use were persistent compared to those without pre-index DMARD (56.1 vs. 33.3 %, p = 0.0001). No significant differences were observed for the AS and PsA cohorts. Multivariate analyses confirmed that DMARD-experienced patients were 2.45 times more likely to be persistent with subcutaneous biologic therapy in the RA cohort. Switching between subcutaneous biologics occurred in <10 % of patients in all three cohorts. In the subpopulations with at least two prescriptions for the index subcutaneous biologic and who remained persistent on the index subcutaneous biologic, dose escalation of ≥50 % occurred in 50, 60, and 49 % in the RA, AS, and PsA cohorts, respectively. Among RA, AS, and PsA patients newly initiating subcutaneous biologic agents in Germany, persistence at 12 months is relatively low (48-58 %). For the RA cohort, patients with pre-index DMARD use are more persistent than patients without. The majority of patients do not switch between subcutaneous biologics. A notable proportion of patients who remained persistent on their index subcutaneous biologic had a dose escalation. There are opportunities to improve outcomes of patient with rheumatoid disease through improved medication persistence.

Reasons for discontinuation of subcutaneous biologic therapy in the treatment of rheumatoid arthritis: a patient perspective.

ObjectiveTo examine reasons why rheumatoid arthritis patients discontinued subcutaneous (SQ) anti-tumor necrosis factor (anti-TNF) treatment in the past 12 months, so as to help inform successful, uninterrupted therapy.MethodsData were collected in March and April 2011 using self-reported, internet-based questionnaires. Study inclusion criteria comprised: rheumatoid arthritis diagnosis; discontinuation of SQ anti-TNF medication (adalimumab, certolizumab, etanercept, or golimumab) within the past 12 months; aged ≥18 years; United States residency; and consent to participate. Patients reported primary and other reasons for discontinuation of their most recently discontinued anti-TNF.ResultsQuestionnaires from 250 patients were analyzed; 72.8% were female, 80.8% were white, and median age was 51 years. Patients had discontinued etanercept (n=109), adalimumab (n=98), certolizumab (n=24), or golimumab (n=19) within the past 12 months. When prompted about their primary reason for discontinuation, lack of effectiveness (40.8%) was cited most often, followed by injection experience (18.4%). Combining prompted primary and other reasons for discontinuation, 60.8% of patients reported lack of effectiveness, while 40.8% reported injection experience, which included: pain/burning/discomfort after injection (14.4%); pain/burning/discomfort during injection (13.2%); injection reactions such as redness/swelling after injection (12.4%); dislike of self-injection (11.6%); dislike of frequency of injection (10.4%); and fear of injection/needles (6.8%).ConclusionFrom the patient perspective, there are unmet needs with regard to the effectiveness and injection experience associated with SQ anti-TNF medications, which may lead to discontinuation. Treatment options with a better injection experience may address these needs. These results demonstrate the importance of including the patient perspective when making prescribing decisions or payer access and coverage decisions.

PMS65 - Persistence Rate With Subcutaneous Biologic Therapies in Patients With Ankylosing Spondylitis (As)

PMS65 - Persistence Rate With Subcutaneous Biologic Therapies in Patients With Ankylosing Spondylitis (As)

AB1077 Treatment Patterns and Persistence with Subcutaneous Biologic Therapies in Patients with Ankylosing Spondylitis

BackgroundAnkylosing Spondylitis (AS) is a chronic, systemic disease that predominantly affects the axial skeleton with sacroiliac joints involvement as its hallmark, causing characteristic inflammatory back pain and resulting in varying...

AB1091 Treatment Persistence with Subcutaneous Biologic Therapies in Patients with Rheumatoid Arthritis

BackgroundSubcutaneous biologic therapies are usually prescribed to patients with moderate to severe Rheumatoid Arthritis (RA), particularly in patients whose condition is not responding to conventional disease-modifying antirheumatic drugs (DMARDs).ObjectivesThe objective...

SAT0089 Cost Minimization Observational Study after Dose Optimization in A Specialized Outpatient Clinic on Subcutaneous Biological Therapy

ObjectivesTo estimate annual cost in the use of subcutaneous BT (scBT) in patients with rheumatic diseases when dose modifications are undertaken in daily practice in a specialized outpatient clinic of...

Cost-minimisation analysis of subcutaneous methotrexate versus biologic therapy for the treatment of patients with rheumatoid arthritis who have had an insufficient response or intolerance to oral methotrexate

This study aims to model the economic impact of subcutaneous methotrexate (SC MTX) or a biologic over a 12-month period using a hypothetical population of rheumatoid arthritis patients who failed to tolerate or respond to oral MTX and were suitable candidates for biologic therapy. A decision-based model was developed using current National Institute for Health and Clinical Excellence (NICE) guidance to determine the management of this hypothetical UK population. Published data on the continuation rates of SC MTX and biologics were used to compare the costs of the two treatment options. The economic model used a cost-minimisation methodology from a UK National Health Service (NHS) perspective, with the cost of all drugs and resources being estimated on this basis. Sensitivity analyses were also performed to determine the effects of changing key assumptions on the mean cost differences. The routine use of SC MTX following oral MTX failure has the potential to save an estimated £7,197 per patient in the first year of therapy and £9.3m per year nationally in new patients. Sensitivity analyses support the robustness of the results. The results of this study suggest that routine use of SC MTX following oral MTX failure has the potential to provide considerable savings to the NHS through optimised use of MTX first-line therapy. It is proposed, therefore, that patients should start on oral MTX with a subsequent switch to SC MTX in the case of an insufficient response or tolerability issues, before introducing a biologic agent.

FRI0182 Non-biologics disease modifying anti-rheumatic drugs (nbdmards) and biologics agents acquisition and adherence among french rheumatoid arthritis patients in real life population: results from a cross-sectional study

BackgroundRecent meta-analysis established that the efficacy of combination therapy with a biological agent is superior to methotrexate for remission (1). Moreover, superiority of combination of anti-TNFa (aTNF) + nbDMARDs over...

AB1367 Persistency with subcutaneous anti-TNF therapy for treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis patients

BackgroundRheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) are chronic autoimmune diseases that result in destructive inflammation of the joints, as well as other organs. Golimumab, adalimumab, and...

AB0724 Safety, pharmacokinetics, and pharmacodynamics of a human anti-IL6 monoclonal antibody PF-04236921 in healthy subjects

BackgroundPF-04236921 is a fully human monoclonal antibody that binds with high affinity to the human interleukin-6 (IL6) ligand, and neutralizes its activity. It is a new subcutaneous (SC) biological therapy...

AB1387 Reasons for discontinuation of subcutaneous biologic therapy in the treatment of rheumatoid arthritis: A patient perspective

BackgroundSeveral factors may lead to discontinuation of biologic therapies by patients with rheumatoid arthritis (RA). The role of these factors in discontinuation of therapy should be examined to determine how...