Autoinjector Improves Injection-related Tolerability Issues in Patients with Multiple Sclerosis

Figure 1: Number of Patients Pain-free After 15 Injections of Interferon Beta-1a 44µg and Interferon Beta-1b 250µg Administered by Autoinjector†10

100

10 20 30 40 50 60 70 80 90

0 100 p<0.0001* p<0.0001* 40.2

p<0.0021* 16.7

4.8 Immediately 30 minutes Interferon β-1a 44µg (n=105) Time after injection

Interferon β-1b 250µg (n=209) 60 minutes

Visual analogue scale (VAS) = 0 for all injections. †In the interferon beta-1b (INFβ-1b) group, data were missing for six patients (2.9%) immediately, 17 (8.1%) at 30 minutes and 25 (12.0%) at 60 minutes after injection, and in the INFβ-1a group for one (1.0%) immediately, five (4.8%) at 30 minutes and nine (8.6%) at 60 minutes. *Descriptive analysis.

using the Betaject reported that they were pain-free at all three time points compared with those using the Rebiject (see Figure 1). These results indicate that INFβ-1b is less painful to inject than INFβ-1a. The study also looked at the effect of needle size on the proportion of pain-free injections: patients who were using INFβ-1b reported more pain-free injections when using a smaller gauge needle – (29–30 rather than 25–27 gauge; see Figure 2). Furthermore, fewer patients using INFβ-1b were reported to have ISRs compared with those using INFβ-1a. After the 15 consecutive injections assessed for the study, 51.8% of the INFβ-1b group versus 33.8% of the INFβ-1a group were reported to have no ISRs (p<0.0001; see Figure 3). Other AEs occurred at similar rates for both types of INFβ.

Another randomised trial compared the occurrence of ISRs in patients with relapsing–remitting MS (RRMS) who were using manual injection or an autoinjector to administer INFβ-1a. The incidence of ISRs was also reduced using an autoinjector compared with a manual injection. In this open-label trial, fewer patients experienced ISRs diagnosed by a physician when using an autoinjector (78.7 versus 85.4%; p<0.001).24 Furthermore, for patient-reported ISRs, a smaller proportion of patients using an autoinjector reported ISRs compared with those using manual injections (66.1 versus 71.8%, p<0.001).

In MS treatment, most autoinjectors and studies evaluating them involve SC injection. An exception to this is an ongoing phase III study that is evaluating a single-use pre-filled autoinjector for intramuscular (IM) injection of INFβ-1a.28

This is an open-label, single-group study

including a planned group 90 patients with MS who are required to administer a weekly dose of INFβ-1a for a 22-day period. The study objectives are to establish whether the autoinjector can be used effectively and safely and will also determine the tolerability of the system, the value of training materials and patient preference relative to manual injection. The results for this study are awaited.

Clinical data also supports the use of smaller gauge needles with a sharper bevel. Jaber et al. have reviewed the use of various types of needles in two clinical studies of healthy subjects and five surveys of patients with MS. The main objective of their review was to assess whether a 29-gauge sharper (five-bevel) needle with a thermoplastic

EUROPEAN NEUROLOGICAL REVIEW 31.4 16.2 55.0

10 20 30 40 50 60 70 80 90

0

Immediately 30 minutes 25–27G

60 minutes Immediately 30 minutes 60 minutes 29–30G

Interferon β-1a 44µg Interferon β-1b 250µg

*91.9% of patients used an autoinjector to administer interferon beta-1a (INFβ-1a) 44µg. †94.4% of patients used an autoinjector to administer INFβ-1b 250µg.

Figure 3: Injection Site Reactions with Interferon Beta-1a 44µg* or Interferon Beta-1b 250µg† after 15 Consecutive Injections

100

10 20 30 40 50 60 70 80 90

0

p=0.0209 p=0.3136 80.7 85.0

77.1 60.9

p=0.0018 41.0

21.1

p=0.0001 50.9

p=0.0001 82.5

p=0.0001 88.9

70.1 52.2

Figure 2: The Effect of Needle Size (25–27 and 29–30 Gauge) on the Proportion of Pain-free Injections per Patient Treated with Interferon Beta-1a 44µg* or Interferon Beta-1b 250µg†10

19.7

64.1 51.8 33.8 46.2

2.1 None Grade 0

Pain, itching or erythema

Grade 1 Interferon β-1a 44µg

2.0

Pain, swelling with inflamation or phlebitis

Grade 2 Interferon β-1b 250µg

*91.9% of patients used an autoinjector to administer interferon beta-1a (INFβ-1a) 44µg. †94.4% of patients used an autoinjector to administer INFβ-1b 250µg. ISRs = injection site reactions.

The two double-blind, randomised clinical studies in healthy volunteers compared the impact of three needle parameters, i.e. gauge, bevel geometry and needle shield material. In these trials, fewer patients perceived ISP (assessed using a VAS and verbal analogue [VB-VAS]) using the 29-gauge/5-bevel needle compared with the 27-gauge/3-bevel needle, with a 40% reduction in VAS pain scores. The use of a narrower needle gauge made a larger difference on both VAS and VB VAS assessment of ISP than the use of a smaller bevel angle, i.e. bevel five scored slightly better than bevel three for both 27- and 29-gauge needles. In addition, needles fitted with a rubber shield were perceived to cause less ISP than the needles with a thermoplastic elastomer shield. Nurses also reported that skin penetration was also improved by 69% with the 29-gauge/five-bevel needle compared with the 27-gauge/three-bevel needle. However, it is important to note that these healthy subjects were just pricked with the various needle sizes and did not receive any injected fluid. The collation of results from the

elastomer shield is an improvement over a 27-gauge less sharp (three-bevel) needle with a rubber shield for the injection of INFβ-1a 44 or 22µg.20

79

Proportion of pain-free patients over 15 injections

Percentage of patients with ISRs

Mean percentage of pain-free injections over 15 injections