Tolerability and safety of novel half milliliter formulation of glatiramer acetate for subcutaneous injection: an open-label, multicenter, randomized comparative study

Abstract

Daily glatiramer acetate (GA) 20 mg/1.0 mL is a first-line treatment for relapsing-remitting multiple sclerosis (RRMS). To reduce the occurrence of injection pain and local injection site reactions (LISRs), a reduced volume formulation of GA was developed. This study compared pain and LISRs after injecting the marketed and the novel formulations. RRMS patients currently injecting GA participated in this multicenter, randomized, crossover comparative study. All patients administered once-daily subcutaneous injections of GA 20 mg/1.0 mL (marketed formulation) or GA 20 mg/0.5 mL (reduced volume formulation) for 14 days. Patients were crossed-over to the alternate treatment for an additional 14 days. Using a Visual Analog Scale (VAS), patients recorded in daily diaries the severity of injection pain immediately and 5 min post-injection, and the presence and severity of LISRs (swelling, redness, itching, lump) within 5 min and 24 h post-injection. VAS pain scores were ranked significantly lower immediately and 5 min after GA 20 mg/0.5 mL injections (p < 0.0001). Although LISRs were rare for both preparations, the severity of reactions ranked significantly lower and fewer symptoms occurred within 5 min and 24 h of using the reduced volume formulation (p < 0.0001). GA injected subcutaneously in a reduced volume formulation is a more tolerable option.Electronic supplementary materialThe online version of this article (doi:10.1007/s00415-010-5779-x) contains supplementary material, which is available to authorized users.

Tolerability of High-Volume Subcutaneous Injections of a Viscous Placebo Buffer: A Randomized, Crossover Study in Healthy Subjects

“…Immediately after the fourth administration, subjects were asked to rank administrations from least [1] to most [4] painful.…”

“…Biotherapeutics are increasingly being used to treat a wide range of serious illnesses requiring chronic drug administration [1][2][3][4]. Biotherapeutics offer several attractive features, including high selectivity and specificity, good solubility and stability, long persistence in the body, and low risk for bioconversion to toxic metabolites [5].…”

“…Biotherapeutics that require regular self-injection are used by patients with various inflammatory diseases [2,13,14], osteoporosis [15], multiple sclerosis [1], and diabetes mellitus [16,17]. Insulin pumps, which deliver a continuous SC infusion, offer an alternative to multiple daily injections for patients with diabetes and have been shown to improve glycemic control and quality of life and reduce vascular complications [16].…”

Randomized Crossover Comparison of Injection Site Pain with 40 mg/0.4 or 0.8 mL Formulations of Adalimumab in Patients with Rheumatoid Arthritis

“…Pain related to subcutaneous injection can be influenced by various factors, including the inactive ingredients of the formulation (e.g., citrate buffer) [9–11], injection volume [12, 13], and needle size and sharpness [14]. A 40 mg/0.4 mL formulation of adalimumab was developed to address pain associated with injection.…”

Evaluating Risks, Costs, and Benefits of New and Emerging Therapies to Optimize Outcomes in Multiple Sclerosis

“…Patients should also be provided support through frequent contact with an MS-specialized nurse or case manager. 87,97,98 Programs that promote symptom management, medication adherence, and a health-promoting lifestyle are important in the overall management of MS. One example of a disease therapy management (DTM) program that incorporated both self-management and medication therapy management components within a structured 7-month program was reported to (a) significantly increase adherence to injectable medications for enrolled patients compared with community pharmacy patients (0.92 vs. 0.86; P < 0.001); (b) significantly improve persistence on therapy for both community (220 days vs. 177 days; …”