Classification and mitigation of negative injection experiences with biologic medications

Abstract

Injection site reactions with biologic medications are encountered with variable frequency. Although there is no clear definition, they commonly manifest with pain and irritation at the injection site. Previously proposed reaction classification systems may be impractical or insufficient, and more intuitive nomenclature may benefit clinical dermatologists and patients. Negative injection experiences (NIE) are common reasons for biologic medication nonadherence. Here we provide clinical classifications and recommendations for mitigating these reactions. We categorized NIEs into the following: (a) physical, due to the needle and injection process, (b) irritant, related to properties of the injected solution, and (c) allergic, both immediate and delayed.

Understanding and Minimising Injection-Site Pain Following Subcutaneous Administration of Biologics: A Narrative Review

“…Of note, any variations in ISP between originator and biosimilar biologics do not appear to reflect any differences in immunogenicity between these agents [23], with biosimilars reported to be effective and well tolerated in maintaining complete remission after the switch from the originator agent [24,25]. pH Bunke et al [26] suggested that the difference between the physiological pH of the tissue at Table 1 Factors contributing to subcutaneous injection-site pain Product-related factors Injection-related factors Patient-related factors • Formulation (ingredients, pH, buffers) [16,17,27,28,40] • Delivery volume [15,[32][33][34] • Needle gauge size [44] • Device type [49][50][51][52][53][54] • Injection speed [55][56][57][58] • Fluid viscosity [55] • Injection angle/technique [59,60] • Temperature of product [62,63] • Allergens [65,66] • Injection frequency [61] • Injection site [35] • Low body weight [68] • Injection anxiety/'needle phobia' [69,70] • Pain catastrophising [72] • Nocebo effect [73,74] • Female gender [67] • Fibromya...…”

“…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][33][34]. The injection volume for a biologic generally ranges from 0.4-2.0 mL although it is typically restricted to B 1.5 mL to prevent injection pain, leakage and tissue distortion [15,35].…”

“…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). For those patients who are fearful of needles, an autoinjector allows injections to be self-administered without the needle being seen [35]. Any reported ISP with these devices varies from being generally comparative to being reduced with autoinjector/PFS devices [49][50][51][52][53][54].…”

“…Repeated use of the same injection site has the potential to increase both irritation and ISP, suggesting the need to rotate injection sites [35]. Injections administered in the thigh are reported as being more painful than identical ones in the abdomen, possibly due to the presence of less adipose tissue on the thighs [34,58] However, small average differences in pain ratings do not appear to lead to a statistical difference in the acceptance of the injection pain [34].…”

“…In some individuals ISP may be related to hypersensitivity which most often occurs within 10 min to 4 h post-injection (deemed 'immediate') or within 24-48 h ('delayed') [35,64]. Latex hypersensitivity to injection devices for biologic therapies are rare but have been reported [65,66].…”