Table 2.
Crossover/sequential trials comparing ISP intensity and other ISRs between biologics administered using CF and CC formulations.
|
Refer-
ences |
Article Type | Study Design | Country | Sample Size | Indication | Interventions and Formulations | Clinical Outcomes at Injection Site | ISP: Key Results | ISRs: Key Results | Key Conclusion | Outcome ISP | Outcome ISRs |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Nash et al. 2016 [26] |
Full text | Two randomi- zed, single-blind, two period crossover studies |
Multi-country | 125 | RA | Adalimumab (CC) Adalimumab (CF) |
Mean pain VAS score % mild/severe pain % unspecified reactions |
Pooled VAS score CC: 3.7 cm; CF: 1.2 cm; Diff: -2.5 cm, 95% CI -3.0 to -2.0, p < 0.001 Mild pain (pooled) CC: 42.6%; CF: 86.9% Severe pain (pooled) CC: 13.9%; CF: 1.6% |
Unspecified reactions CC: 0.0% (study 1), 0.0% (study 2) CF: 0.0% (study 1), 3.3% (study 2) |
The citrate-free adalimumab formulation was well tolerated and associated with less injection site pain than the citrate-containing adalimumab formulation. | Signif. positive for CF | Balanced |
| Muñoz et al. 2018 [25] |
Abstract | Open-label, single-arm, sequential trial | Un-known | 27 | Psoriasis, spondylitis, Crohn’s disease, PsA | Adalimumab (CC) Adalimumab (CF) |
Mean pain VAS score |
VAS score Diff: −3.0 cm, 95% CI -4.2 to −1.9, p<0.001 |
The auto-injection pen with citrate-free buffer was reported as superior to pre-filled syringe with citrate-containing buffer in terms of perceived injection site pain intensity. | Signif. positive for CF | NA |
Abbreviations: CC, citrate-containing; CF, citrate-free; ISE, injection site erythema; ISP, injection site pain; ISR, injection site reaction; PsA, psoriatic arthritis; RA, rheumatoid arthritis; VAS, Visual Analogue Scale. Significant results were stated as reported in the respective publication; results were interpreted as balanced if the per cent difference between CF and CC formulation outcomes was <5.0%.