A novel needle for subcutaneous injection of interferon beta-1a: effect on pain in volunteers and satisfaction in patients with multiple sclerosis

BMC Neurology BioMed Central Technical advance Open Access A novel needle for subcutaneous injection of interferon beta-1a: effect on pain in volunteers and satisfaction in patients with multiple sclerosis Amer Jaber*1,4, Gian B Bozzato^1, Lionel Vedrine2, Wes A Prais2, Julie Berube2 and Philippe E Laurent3 Address: 1Merck Serono International S.A., Geneva, Switzerland, 2BD Medical – Pharmaceutical Systems, Franklin Lakes, NJ, USA, 3BD Medical – Pharmaceutical Systems, Le Pont de Claix, France and 4UCB Pharma SA, Chemin du Foriest, 1420 Braine l'Alleud, Belgium Email: Amer Jaber* - ; Gian B Bozzato - ; Lionel Vedrine - ; Wes A Prais - ; Julie Berube - ; Philippe E Laurent - * Corresponding author ^Deceased Published: 10 October 2008 BMC Neurology 2008, 8:38 doi:10.1186/1471-2377-8-38 Received: 27 March 2008 Accepted: 10 October 2008 This article is available from: http://www.biomedcentral.com/1471-2377/8/38 © 2008 Jaber et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: To reduce injection pain and improve satisfaction, a thinner (29-gauge [29G]), sharper (5-bevel) needle than the 27G/3-bevel needle used previously to inject interferon (IFN) beta-1a, 44 or 22 mcg subcutaneously (sc) three times weekly (tiw), was developed for use in multiple sclerosis (MS). Methods: Two clinical trials in healthy volunteers and five surveys of patients with MS were conducted to assess whether the 29G/5-bevel needle with a Thermo Plastic Elastomer (TPE) needle shield (a sleeve that houses the tip of the needle in a secure location) is an improvement over the 27G/3-bevel needle with a rubber shield for injection of IFN beta-1a, 44 or 22 mcg sc tiw. Parameters assessed were: pain and ease of insertion (healthy volunteer and nurse responses on subjective pain measurement scales); and patient satisfaction (surveys of patients with MS). Results: In healthy volunteers, the 29G/5-bevel needle with TPE shield was associated with the least perceived pain on the Visual Analog Scale (VAS) and Verbal VAS (VB-VAS); mean VAS pain scores decreased by 40% and skin penetration improved by 69% compared with the 27G/3-bevel needle with standard rubber shield (p < 0.01). Pooled results from surveys of patients with MS indicated that 63% of patients thought that injections were less painful with the 29G/5-bevel needle than the 27G/3-bevel needle. Results from individual surveys indicated that the 29G/5-bevel needle was an improvement over the 27G/3-bevel needle for ease of insertion, injection-site reactions, bruising, burning and stinging. Conclusion: Together these studies indicate that the 29G/5-bevel needle with the TPE shield is an improvement over the 27G/3-bevel needle with standard rubber shield in terms of pain, ease of insertion and patient satisfaction. These improvements are expected to result in improved compliance in patients with MS treated with IFN beta-1a, 44 or 22 mcg sc tiw. Page 1 of 12 (page number not for citation purposes) BMC Neurology 2008, 8:38 Background Although details of the frequency of the injections and delivery systems differ, all disease-modifying drugs (DMDs) approved for the treatment of relapsing forms of multiple sclerosis (MS) are currently administered by injection, some of which can be self-administered by the patient. A patient's perception of the pain caused by drug delivery may directly influence convenience, compliance and acceptance of interventions with proven efficacy. Accordingly, research efforts have focused on improving the design of existing needles to reduce injection-associated pain without compromising the needle's functional integrity. For patients treated with interferon beta-1a (IFN β-1a; Rebif®, Merck Serono International S.A., Geneva, Switzerland [an affiliate of Merck KGaA, Darmstadt, Germany]), 44 or 22 mcg subcutaneously (sc) three times weekly (tiw), a syringe (BD Hypak Physiolis™, Becton Dickinson and Company) has been developed that is fitted with a needle that is thinner (29-gauge [29G]) and sharper (5bevel) than the previous 27G/3-bevel needle but which maintains the same flow rate. The other unique feature of the system is the rigid needle shield made from a Thermo Plastic Elastomer (TPE) instead of rubber. The rigid needle shield is the guarantee of the quality preservation of the needle and makes needle shield removal very intuitive, thus limiting the risk of damaging the needle point. The 'gauge' of a needle indicates its thickness – the higher the gauge, the thinner the needle. Maintenance of the flow rate with the thinner 29G/5-bevel needle is made possible by technological improvements that allow the inner diameter of the 29G/5-bevel needle to be the same as that for the 27G/3-bevel needle, although the outer diameter is reduced. Maintenance of the inner diameter also means that the same pressure is required to inject fluid once the skin has been penetrated. The '5-bevel' means that the tip is cut at five different angles, making it sharper than the previous 3-bevel design. Indeed, engineering tests using synthetic skin showed that the force required to penetrate the skin is reduced by 19–23% using the 5-bevel needletip design compared with a 3-bevel needle [1]. Furthermore, surveys of patients with MS support improved skin penetration and indicate that the 29G/5-bevel needle is less painful than the 27G/3-bevel needle [2] when injecting IFN β-1a, 44 or 22 mcg sc tiw. The 29G/5-bevel needle was first made available to patients with MS in 2004 for the injection of IFN β-1a, 44 or 22 mcg sc tiw, and became available globally at the beginning of 2005. It was expected that using the 29G/5bevel needle would reduce injection pain and make needle insertion easier, resulting in improved patient compliance. Accordingly, seven studies (two clinical trials in http://www.biomedcentral.com/1471-2377/8/38 healthy volunteers and five surveys of patients with MS) were conducted to find out whether the 29G/5-bevel needle is, in practice, an improvement over the previous 27G/ 3-bevel needle in terms of pain, ease of insertion and patient satisfaction. We also assessed the reliability of three subjective pain measurement scales. We present here the results of these seven separate studies of the 29G/5bevel needle. Methods In total, seven separate studies were conducted to assess the 29G/5-bevel needle: two double-blind, randomized, clinical trials in healthy volunteers to assess injectionassociated pain with the 27G and 29G needles and validate the reliability of three subjective pain measurement scales (one single-center trial in France, and a multi-center study in France and the USA); and five surveys in four countries (Australia, Denmark, Germany and the US (...truncated)