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

Clair-Jones, Anja St; Prignano, Francesca; Gonçalves, João; Paul, Muriel; Sewerin, Philipp

doi:10.1007/s40744-020-00245-0

Cited by 60 publications

(35 citation statements)

References 90 publications

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“…SC vedolizumab contains citrate which has been pointed out to be causing pain, but studies that have addressed this issue underscore that citrate is merely one of several factors that may affect potential pain sensation at SC injection and that some of the studies attributing pain at the injection site to citrate are difficult to interpret since citrate was one of several factors modified 42–44 . Other factors that may be equally important in this context are other buffers commonly used such as phosphate and histidine, the buffer concentration, injected volume, solution temperature, pH, osmolality, needle gauge, injector device, injection speed, injection technique and low body weight 42–44 …”

Section: Discussionmentioning

confidence: 99%

Real‐world data on switching from intravenous to subcutaneous vedolizumab treatment in patients with inflammatory bowel disease

Bergqvist

Holmgren

Klintman

et al. 2022

Aliment Pharmacol Ther

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Summary Background and Aims Vedolizumab is a gut‐selective treatment approved for Crohn’s disease (CD) and ulcerative colitis (UC). Recently, a subcutaneous formulation of vedolizumab was approved. The aims of this study were to evaluate efficacy, safety, pharmacokinetics, patient experience and costs following a switch from intravenous to subcutaneous vedolizumab treatment. Methods Patients were switched from intravenous to subcutaneous vedolizumab maintenance treatment and followed prospectively for 6 months and a subgroup for 12 months. The primary endpoint was change in faecal calprotectin levels. Furthermore, we evaluated clinical disease activity, remission rates, plasma CRP, drug persistence, adverse events, local injection reactions, serum drug concentrations, patient satisfaction, quality‐of‐life and treatment costs. Results Eighty‐nine patients were included (48 CD; 41 UC). Faecal calprotectin decreased significantly in CD but not in UC. Clinical indices, remission rates, plasma CRP levels and quality‐of‐life scores remained unchanged. Patients that had been on standard compared to optimised IV vedolizumab dosing displayed similar outcomes on standard SC dosing. Drug persistence at 6 and 12 months was 95.5% and 88.5%, respectively. Frequencies of adverse events were similar before and after the switch. No serious adverse events occurred. Transient severe local injection reactions were experienced by 1.2% of patients. Median vedolizumab trough levels were 2.3 times higher on subcutaneous compared to intravenous treatment. Patient satisfaction was generally high. Annualised treatment costs were reduced by 15% following the switch. Conclusions The switch from intravenous to subcutaneous vedolizumab could be done with preserved therapeutic effectiveness, safety, high patient satisfaction and low discontinuation rate, at a reduced cost.

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Section: Discussionmentioning

confidence: 99%

Real‐world data on switching from intravenous to subcutaneous vedolizumab treatment in patients with inflammatory bowel disease

Bergqvist

Holmgren

Klintman

et al. 2022

Aliment Pharmacol Ther

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“… 19 It is recognised that pain perception is subjective and multiple factors may influence this, including the inclusion of citrate as an excipient, volume of injection, and needle size. 25 There may be differences in injection-related pain between the prefilled pens or syringes. Patients were offered the choice of either formulation to administer their medication, and the opportunity to try a different formulation if the first was not tolerated.…”

Section: Discussionmentioning

confidence: 99%

Transitioning from Intravenous to Subcutaneous Vedolizumab in Patients with Inflammatory Bowel Disease [TRAVELESS]

Ventress

Young

Rahmany

et al. 2021

Journal of Crohn's and Colitis

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Background and Aims Subcutaneous (SC) vedolizumab presents the opportunity for inflammatory bowel disease (IBD) patients to manage their treatment at home. There is currently no data on the process of transitioning patients established on intravenous (IV) to SC as part of routine clinical care. The aim of this programme is to evaluate the clinical and biochemical outcomes of switching a cohort of IBD patients established on IV vedolizumab to SC 12 weeks following the transition. Methods 178 adult patients were offered the opportunity to transition to SC vedolizumab. Patients who agreed were reviewed prior to switching and at week 12 (W12) after their first SC dose. Evaluation outcomes included disease activity scores, the IBD-Control patient-reported outcome measures (PROMs) and faecal calprotectin (FCP). Reasons for patients declining or accepting transitioning, pharmacokinetics, adverse drug reactions and risk factors for a poor outcome in SARS-CoV-2 infection were also assessed. Results 124 patients agreed to transition, of which 106 patients had been on IV vedolizumab for at least 4 months. There were no statistically significant differences in disease activity scores or IBD-Control PROMs between baseline and W12. A statistically significant increase in FCP was observed (31µg/g vs. 47µg/g; p=0.008), although this was unlikely to be clinically relevant. The most common adverse drug reaction reported was injection site reactions (15%). Based on this cohort of patients, an expected reduction of £572,000 per annum is likely to be achieved. Conclusions Transitioning patients established on IV vedolizumab to SC appears to be safe and effective, with high patient satisfaction and multiple benefits for the health service.

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“…Those reactions mostly diminished in both groups after 15 min (Supplement 1). Factors known to contribute to subcutaneous injection site reactions can be grouped into product-related and patient-related factors (e.g., low body weight or needle phobia) [ 12 ]. The product-related factors include the formulation (ingredients, pH, or buffers), injection volume, needle gauge size, or type of device.…”

Section: Discussionmentioning

confidence: 99%

A Randomized Pharmacokinetic Study in Healthy Male Subjects Comparing a High-concentration, Citrate-free SB5 Formulation (40 mg/0.4 ml) and Prior SB5 (Adalimumab Biosimilar)

et al. 2022

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Introduction: SB5 is an approved biosimilar of adalimumab, a monoclonal anti-tumor necrosis factor (anti-TNF) antibody. This study compared pharmacokinetics (PK), safety, tolerability, and immunogenicity between a new highconcentration, low-volume, and citrate-free formulation (40 mg/0.4 ml, SB5-HC) and the current low-concentration formulation with higher volume (40 mg/0.8 ml, SB5-LC) to evaluate the bioequivalence of the two formulations. Methods: This study was a randomized, singleblind, two-arm, parallel-group, single-dose study in healthy male subjects. Subjects were randomized to receive either SB5-HC or SB5-LC via subcutaneous injection using a pre-filled syringe. Primary endpoints were the area under the curve of the concentration-time curve from zero to infinity (AUC inf ) and maximum serum concentration (C max ). Bioequivalence was achieved if the 90% confidence intervals (CIs) for the ratios of the geometric least squares mean (LSMean) of primary endpoints were within the pre-defined bioequivalence margins of 0.80-1.25. Secondary endpoints included safety, tolerability, and immunogenicity. Results: Subjects (n = 188) were randomized to SB5-HC (n = 94) or SB5-LC (n = 94). Baseline characteristics were comparable between the two treatment groups. The mean values for AUC inf and C max were similar between the SB5-HC and SB5-LC groups. For the primary endpoints, the geometric LSMean ratios (90% CI) for AUC inf and C max were 0.920 (0.8262-1.0239) and 0.984 (0.9126-1.0604), respectively, placing the corresponding 90% CIs well within the pre-defined bioequivalence margin of 0.80-1.25. All treatment-emergent adverse events (TEAEs) were considered mild to moderate and were reported for 44.7% and 51.1% of subjects in the SB5-HC and SB5-LC groups, respectively. Immunogenicity assessed by frequency of occurrence of anti-drug antibodies (ADAs) and neutralizing antibodies (NAbs) was comparable between groups.Conclusions: This bridging study demonstrated PK equivalence and comparable safety and tolerability of subcutaneous injection of SB5 via SB5-HC or SB5-LC. Clinicaltrials.gov identifier: https://clinicaltrials. gov/ct2/show/NCT04514796.

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

Cited by 60 publications

References 90 publications

Real‐world data on switching from intravenous to subcutaneous vedolizumab treatment in patients with inflammatory bowel disease

Real‐world data on switching from intravenous to subcutaneous vedolizumab treatment in patients with inflammatory bowel disease

Transitioning from Intravenous to Subcutaneous Vedolizumab in Patients with Inflammatory Bowel Disease [TRAVELESS]

A Randomized Pharmacokinetic Study in Healthy Male Subjects Comparing a High-concentration, Citrate-free SB5 Formulation (40 mg/0.4 ml) and Prior SB5 (Adalimumab Biosimilar)

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