If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
This article has been cited by other articles in PMC. Abstract Injection-site pain ISP is a subjective side effect that is commonly reported with the subcutaneous administration of biological agents, yet it may only be a concern to some. Key Summary Points Injection-site pain ISP is a commonly reported subjective side effect with the subcutaneous SC administration of biological agents, yet it may only be a concern to some.
Multiple factors, including those related to product formulation e. While total elimination of ISP remains unlikely, it can be minimised by helping the patient develop a competent injection technique and by lowering their treatment-related anxieties. Other interventions to help minimise ISP include psychological interventions, allowing biologics to reach room temperature prior to injection, using the injection device most suitable for the individual patient and selecting an alternative drug formulation, when available.
Open in a separate window. Digital Features This article is published with digital features, including a summary slide, to facilitate understanding of the article. Introduction Biological agents have revolutionised treatment across a range of immune- and inflammatory-mediated diseases [ 1 — 4 ], and the efficacy and manageable side-effect profiles of these agents have led to them being recommended in treatment guidelines [ 5 — 9 ].
Table 1 Factors contributing to subcutaneous injection-site pain. Product-Related Factors Contributing to SC ISP Product-related factors vary widely between biologics, but also between different approved products containing the same active ingredient, such as a reference product and a biosimilar. Table 2 Variability in product-related factors contributing to injection-site pain across available references for and biosimilar formulations of a adalimumab and b etanercept.
Buffers Buffers, such as citrate and phosphates, are frequently added to parenteral formulations to optimise solubility and stability by adjusting the pH.
Volume Higher volumes of injection are typically associated with increased patient discomfort and sometimes pain at the site of administration, with less ISP reported where reduced volume is possible [ 15 , 32 — 34 ]. Other Excipients The use of some excipients to support product stability, such as polysorbates, glutamate and serum, have also been associated with ISP and injection-site reactions in some studies [ 36 — 38 ]. Needle The frequency of a painful needle insertion has been directly correlated with needle diameter [ 44 ].
Device Type Preference for the type of device used to administer SC injections can vary from patient to patient, with options including pre-filled syringes PFS and autoinjectors such as pre-filled pens PFP. Frequency of Injection Frequency of injection can also impact pain perception. Injection Site Repeated use of the same injection site has the potential to increase both irritation and ISP, suggesting the need to rotate injection sites [ 35 ].
Challenges in Assessing ISP Pain, including ISP, is a complex perceptual phenomenon and a subjective experience and, consequently, it is difficult to describe and accurately measure [ 76 ].
Table 3 Examples of ISP variability across biologic agent disease area when administered subcutaneously. Patient Training First and foremost, this can be achieved by providing effective patient training to ensure a confident, competent and consistent injection technique.
Psychological Intervention There are no published studies of simple psychological interventions for ISP in adults, although some evidence from studies on other needle procedures show a benefit from breathing strategies and neutral signaling of the start of the procedure [ 81 ]. Patient Movement and Muscle Stiffness Attempts to minimise patient movement and muscle stiffness, which are often associated with higher anxiety levels, during the SC injection process may help to lessen any ISP given that body movement and anxiety have correlated with verbal pain intensity ratings [ 87 ].
Managing Patient Expectations Patient expectations of potential ISP with any given SC biologic need to be carefully managed given that adherence to these agents can be influenced by ISP and skin perception, with misconceptions of SC routes of administration negatively impacting treatment adherence [ 77 , 78 ].
Summary Injection-site pain is a commonly reported, yet subjective, side effect associated with the SC administration of drugs, including biologic agents. Editorial Assistance Editorial assistance in the preparation of this manuscript was provided by Matthew Joynson of Springer Healthcare Ltd. Authorship All named authors meet the International Committee of Medical Journal Editors ICMJE criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.
Authorship Contributions All authors contributed to the creation and critical review of the manuscript. Disclosures Anja St Clair-Jones has no current personal, commercial, academic, or financial interests to disclose. Compliance with Ethics Guidelines This review is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors therefore ethical approval was not required. References 1. Biologics in inflammatory bowel disease: what are the data?
United Eur Gastroenterol J. Immune-mediated inflammatory diseases IMIDs and biologic therapy: a medical revolution. Postgrad Med J. Role of biological agents in treatment of rheumatoid arthritis. Pharmacol Res. Old and new biological therapies for psoriasis. Int J Mol Sci. Third European evidence-based consensus on diagnosis and management of ulcerative colitis.
Part 2: current management. J Crohns Colitis. J Am Acad Dermatol. Arthritis Rheumatol. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: update. Ann Rheum Dis. ECCO guidelines on therapeutics in Crohn's disease: medical treatment. Subcutaneous administration of biotherapeutics: an overview of current challenges and opportunities.
Rodger MA, King L. Drawing up and administering intramuscular injections: a review of the literature. J Adv Nurs. Are there differences in immunogenicity and safety of vaccines according to the injection method? Med Mal Infect. Armstrong AW, Read C.
Pathophysiology, clinical presentation, and treatment of psoriasis: a review. TNF-alpha blockers in inflammatory bowel diseases: practical consensus recommendations and a user's guide.
Swiss Med Wkly. Subcutaneous injection volume of biopharmaceuticals-pushing the boundaries. J Pharm Sci. Decreased injection site pain associated with phosphate-free etanercept formulation in rheumatoid arthritis or psoriatic arthritis patients: a randomized controlled trial. Klement W, Arndt JO. Pain on IV injection of some anaesthetic agents is evoked by the unphysiological osmolality or pH of their formulations. Br J Anaesth. Assessment report.
Accessed 15 Feb Comparison of injection-site reactions between the etanercept biosimilar SB4 and the reference etanercept in patients with rheumatoid arthritis from a phase III study. Br J Dermatol. Comparison of the pharmacokinetics, safety, and immunogenicity of MSB, a biosimilar of adalimumab, with Humira R in healthy subjects. Br J Clin Pharmacol. Medical review. Injection site reactions and injection site pain for the adalimumab biosimilar ABP results from two double-blind, randomised, controlled studies.
Immunogenicity of biosimilars for rheumatic diseases, plaque psoriasis, and inflammatory bowel disease: a review from clinical trials and regulatory documents. Maintenance of clinical remission with SB5 biosimilar after switch from adalimumab originator: real-life experience of a tertiary referral center.
Long-term follow-up of switching from original adalimumab to adalimumab biosimilar: real-world data in IBD. Buffered local anesthetics reduce injection pain and provide anesthesia for up to 5 hours. J Plast Reconstr Aesthet Surg. Impact of pain associated with the subcutaneous administration of adalimumab. Gastroenterol Hepatol. Different failure rates after non-medical switching of patients from adalimumab originator to 2 different adalimumab biosimilars at Cambridge University Hospitals, UK: real world experience.
Regional medicines optimisation committee briefing, best value biologicals: adalimumab update 6. Subcutaneous injection of drugs: literature review of factors influencing pain sensation at the injection site. Adv Ther. Tolerability and safety of novel half milliliter formulation of glatiramer acetate for subcutaneous injection: an open-label, multicenter, randomized comparative study. J Neurol. Pain assessment of subcutaneous injections. Direct-to-consumer advertising of pharmaceuticals Allergan has persevered with the Principle is a The method utilized for performing the assay is specific to Allergan's product, Use professional pre-built templates to fill in and sign documents online faster.
Get access to thousands of forms. USLegal fulfills industry-leading security and compliance standards. Ensures that a website is free of malware attacks. Highest customer reviews on one of the most highly-trusted product review platforms.
TopTenReviews wrote "there is such an extensive range of documents covering so many topics that it is unlikely you would need to look anywhere else". USLegal received the following as compared to 9 other form sites.
If you get weekly or monthly shots on a regular schedule without missing doses, you're less likely to have a serious reaction. Taking an antihistamine medication before getting your allergy shot can reduce the risk of a reaction, particularly a local reaction.
Check with your doctor to see if this is recommended for you. The possibility of a severe reaction is scary — but you won't be on your own. You'll be observed in the doctor's office for 30 minutes after each shot, when the most serious reactions usually occur. If you have a severe reaction after you leave, return to your doctor's office or go to the nearest emergency room.
Administer epinephrine if recommended by your physician. Before starting a course of allergy shots, your doctor will use a skin test or blood test to determine that your reactions are caused by an allergy — and which specific allergens cause your signs and symptoms. During a skin test, a small amount of the suspected allergen is scratched into your skin and the area is then observed for about 15 minutes.
Swelling and redness indicate an allergy to the substance. When you go in for allergy shots, let the nurses or doctors know if you are feeling unwell in any way. This is especially important if you have asthma. Also let them know if you had any symptoms after a previous allergy shot. More recent reports by Reid et al. Factors as specified in previous two paragraphs, played a role in the fatalities at medical facilities. In contrast, other reviews and studies have reported the safety of regimens established for self-administered IT.
The selection of a low-risk patient population is a common finding in clinical studies and reviews that have demonstrated safe outcomes. This conclusion is further corroborated by noting the results of a large, prospective, self-administered SCIT study in which approximately , patient encounters and 1,, allergy injections were studied. The authors further concluded that home-based IT was found to be safe.
The authors concluded that home-based SCIT is a safe treatment option in low-risk patients. A few sources have previously criticized specific studies in which the formulated IT was suspected to use low concentrations of extracts.
Historically, a higher proportion of SRs have been reported to occur during the buildup phase. Alternatively, of note, the rate of dose increase during the buildup phase is considered a prominent cause of induced SRs. European IT practices have traditionally used aluminum adjuvants and more recently other depot adjuvants such as tyrosine for allergoid SCIT. Consistent with the aforementioned recommendations and concepts, the UAS protocol uses a buildup phase in which maintenance is achieved in 6 months, longer than some promulgated regimens but still consistent with the recent IT practice parameters.
This protocol uses cumulative dosing equivalent to that recommended by the practice parameters as evident in Table 2. We hypothesize that this slower buildup phase is both safe and efficacious. To substantiate this concept, further investigation of the potential safety and efficacy of a slower IT buildup phase is warranted.
The safety and efficacy of SLIT immunotherapy is well documented in the literature and is an alternative route of IT administration. As summarized above, several studies have demonstrated increased safety outcomes for self-administered SCIT during the IT maintenance phase. Only 2 of the affected adult population experienced more severe adverse events 1 grade III and 1 grade IV. These results are consistent with several previous reports, 30 , 40 , 50 , 51 but not all.
Furthermore, only 1 asthmatic patient presented with respiratory symptoms mild dyspnea as part of her SR, which were readily addressed therapeutically. All adverse events were effectively treated without sequelae. With respect to the individuals with grade II SRs who did not use epinephrine, none met the criteria for anaphylaxis. In addition, Winther et al. Potential conflict of interest: F.
National Center for Biotechnology Information , U. Int Forum Allergy Rhinol. Author manuscript; available in PMC Feb 1. Frederick M. Schaffer , MD, 1, 2 Andrew R. Hulsey , ScD, 3 and Larry M. Garner , BA 1. Andrew R. Thomas C.
Larry M. Author information Copyright and License information Disclaimer. Correspondence to: Frederick M. Copyright notice. The publisher's final edited version of this article is available at Int Forum Allergy Rhinol. See other articles in PMC that cite the published article. Abstract Background Self-administered allergen immunotherapy is considered controversial. Methods We analyzed 23, patient records and associated immunotherapy injections for systemic reactions SR during a 1-year period to Results Thirty-seven SRs were reported for 23, patients who self-administered 2,, injections yielding an annual SR rate of 0.
Conclusion We believe this safety profile is due to a preselection of patients to exclude those with a high risk for adverse reactions and a slow immunotherapy buildup phase. Keywords: self-administration, allergen immunotherapy, safety, systemic reaction, epinephrine. Patients and methods United Allergy Services UAS facilitates primary care physicians with allergy assessment and therapy. Data collection and reporting All records pertaining to the treatment of patients are collected and stored in the cloud-based database software, SalesForce SalesForce.
Open in a separate window. Immunotherapy Immunotherapy solutions contained allergen extracts defined by patient history, symptomology, environmental exposure, and SPT results. IT protocol The UAS self-administration protocol encompasses several subcutaneous injections per week during the buildup phase for 6 months, at which point maintenance dosing is achieved.
Compliance To promote safety and compliance, all patients are only given a single unit-dose vial set and a preprinted IT injection log book that enumerates all required doses eg, volume and frequency of each subcutaneous injection administration to take home. Results Patients A thorough review revealed that 23, patients were approved and undergoing self-administered IT during the study period of to IT dosing Table 2 shows a comparison of the UAS initial annual cumulative dosing during the 6 months of the buildup phase plus the 6 months of maintenance vs the recommended practice parameters cumulative dose achieved during the buildup and maintenance phases 4 months of buildup and 8 months of maintenance.
Discussion To the best of our knowledge, this is the largest study reporting the safety outcome of a self-administered SCIT protocol for a patient cohort consisting of tens of thousands of individuals.
Footnotes Potential conflict of interest: F. References 1. Mechanisms of subcutaneous allergen immunotherapy.
0コメント