Table 3.
Head-to-head comparison trials regarding ISP intensity and other ISRs between biologics administered using CF and CC formulations.
| Reference | Article Type | Study Design | Country | Sample Size | Indication | Biologic Intervention(s) and Formulations | Clinical Outcomes at Injection Site | ISP: Key Results | ISRs: Key Results | Key Conclusion | Outcome ISP | Outcome ISRs |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Krishnan et al. 2018 [28] |
Abstract | Two randomized, double-blind, active-controlled clinical trials | USA | 876 | RA; PsO | Adalimumab (CC) Adalimumab (CF) |
Mean pain VAS score % overall reactions |
VAS score RA patients: CC: 16.1-21.4 mm; CF: 10.0-10.7 mm PsO patients: CC: 12.4-19.3 mm; CF: 3.3-4.5 mm |
Overall reactions RA patients: CC: 5.0%; CF: 2.3% PsO patients: CC: 5.2%; CF: 1.7% |
Frequency of ISRs and perception of ISP were lower with the CF biosimilar compared with the CC adalimumab reference. | Positive for CF | Balanced |
| Weinblatt et al. 2013 [29] | Full text | Multinational, prospective, randomized, Phase 3 | Multi-country | 646 | RA | Adalimumab + MTX (CC) Abatacept + MTX (CF) |
% pain % overall reactions % erythema % pruritus % hematoma % unspecified reactions |
Pain CC: 2.4%; CF: 0.0% |
Overall reactions CC: 9.1%; CF: 3.8% Erythema CC: 4.3%; CF: 0.6% Pruritus CC: 2.1%; CF: 0.3% Hematoma CC: 0.9%; CF: 1.6% Unspecified reactions CC: 1.2%; CF: 0.9% |
Significantly more local overall ISRs occurred in patients treated with the CC adalimumab formulation. | Balanced | Signif. positive for CF |
| Griffiths et al. 2015 [27] |
Full text | Two double-blind, multicenter, placebo-controlled Phase 3 trials | Multi-country | 2,562 | Chronic PsO | Ixekizumab Q2W (CC) Ixekizumab Q4W (CC) Etanercept (CF) |
% pain % erythema % unspecified reactions |
Pain CC: 3% (Q2W), 1% (Q4W); CF: 1%; Placebo: 1% |
Overall reactions CC: 17% (Q2W), 13% (Q4W); CF: 16%; Placebo: 4% Erythema CC: 3% (Q2W), 12% (Q4W); CF: 4%; Placebo: 1% Unspecified reactions CC: 10% (Q2W), 9% (Q4W); CF: 11%; Placebo: 1% |
Although injection site reactions were among the most common adverse reactions recorded after receiving ixekizumab, occurrences were similar to those in patients given etanercept and were mild or moderate in severity. | Balanced | Balanced |
Abbreviations: CC, citrate-containing; CF, citrate-free; ISE, injection site erythema; ISP, injection site pain; ISR, injection site reaction; MTX, methotrexate; PsO, plaque psoriasis; 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%.