Efficacy and safety evaluations of adalimumab biosimilars in the treatment of psoriasis

Figures & data

Figure 1. Graph summary of the risk of bias.

Figure 2. Assessment chart of the percentage risk of bias.

Table 1. Quality assessment of the included studies.

First author and publication year	Generation of random sequences	Allocation concealment	Blinding of investigators and subjects	Blinding of outcome assessment	Integrity of outcome data	Selective reporting of research findings	Other types of bias	Score on Jadad scale
Cai 2021 [22]	Central Interactive Web Response System	Not clear	Blind	Blind	Complete description of loss to follow-up and withdrawal	Entire	Not clear	3
Feldman 2021 [23]	Interactive Voice/Web Response System	Not clear	Blind	Blind	Complete description of loss to follow-up and withdrawal	Entire	Not clear	3
Menter 2020 [24]	Interactive Response System	Random code	Blind	Blind	Complete description of loss to follow-up and withdrawal	Entire	Not clear	4
Hercogová 2019 [25]	Central Interactive Web Response System	Arranged Blocks Centrally Generated	Blind	Blind	Complete description of loss to follow-up and withdrawal	Entire	Not clear	4
Papp 2017 [26]	Computer	Interactive Voice/Web Response System	Blind	Blind	Complete description of loss to follow-up and withdrawal	Entire	Not clear	4
Papp 2017 [27]	Not clear	Not clear	Blind	Blind	Complete description of loss to follow-up and withdrawal	Entire	Not clear	3
Samtsov 2022 [28]	Not clear	Not clear	Blind	Blind	Complete description of loss to follow-up and withdrawal	Entire	Not clear	4
Blauvelt 2018 [29]	Not clear	Not clear	Blind	Blind	Complete description of loss to follow-up and withdrawal	Entire	Not clear	3

Figure 3. Flow chart of the literature screening process.

Table 2. Characteristics of included studies.

First author and publication year	Stage	Group	Entry conditions	Number of cases		Age, years	Interventions	Treatment duration	BSA, %	PASI, points	Outcomes
				Males	Females
Cai 2021 [22]	1	Test	BSA ≥10%, PASI ≥12 points, PGA score ≥3 pointsBSA ≥10%, PASI ≥12 points, PGA score ≥3 points	190	71	38 (18.0–74.0)	HLX 03 at 80 mg ih in week 1, then 40 mg ih every 2 weeks	16 weeks	40.0 (29.0–59.0)	24.3 (18.0–32.9)	②⑤⑥⑨ ⑩⑪
		Control				38.5 (19.0–71.0)	Humira at 80 mg ih in week 1, then 40 mg ih every 2 weeks		35.3 (22.4–49.0)	20.4 (14.9–26.1)
	2	Test	Continue stage-1 test group				HLX 03 at 40 mg ih every 2 weeks	Weeks 17–48
		Control	Continue stage-1 control group				Humira at 40 mg ih every 2 weeks
Feldman 2021 [23]	1	Test	BSA ≥10%, PASI ≥12 points, PGA score ≥3 points	254	158	42.0 (20–71)	AVT 02 at 80 mg ih in week 1, then 40 mg ih every 2 weeks	16 weeks	28.0 (10–86)	21.60 (12.1–55.9)	⑤⑥⑦⑨ ⑩⑪
		Control	BSA ≥10%, PASI ≥12 points, PGA score ≥3 points			43.0 (18–70)	Humira at 80 mg ih in week 1, then 40 mg ih every 2 weeks		26.0 (10–84)	20.80 (12.0–55.2)
	2	1*	In the test group of stage 1, PASI-50 patients continued	245	147	42.0 (20–71)	AVT 02 at 40 mg ih every 2 weeks	Weeks 17–48	28.0 (10–83)	21.60 (12.1–51.0)
		2^#	In the control group of stage 1, PASI-50 patients were randomly assigned			42.0 (18–70)	Humira at 40 mg ih every 2 weeks		28.0 (10–82)	21.25 (12.0–46.0)
		3^Δ	In the control group of stage 1, PASI-50 patients were randomly assigned			43.0 (22–69)	AVT 02 at 40 mg ih every 2 weeks		25.0 (10–84)	19.80 (12.1–55.2)
Menter 2020 [24]	1	Test	BSA ≥10%, PASI ≥12 points, PGA score ≥3 points	203	114	18–80	BI 695501 at 80 mg ih in week 1, then 40 mg ih every 2 weeks	1–16 weeks			①②③④ ⑤⑥⑩⑪
		Control	BSA ≥10%, PASI ≥12 points, PGA score ≥3 points				Humira at 80 mg ih in week 1, then 40 mg ih every 2 weeks
	2	1*	In the test group of stage 1, PASI-50 patients continued				BI 695501 at 40 mg ih biweekly	17–24 weeks
		2^#	In the control group of stage 1, PASI-50 patients continued				Humira at 40 mg ih every 2 weeks
Author and publication date	Stage	Group	Entry conditions	Number of cases		Age, years	Interventions	Treatment duration	BSA, %	PASI, points	Outcomes
				Males	Females
Hercogová 2019 [25]	1	Test	BSA ≥10%, PASI ≥12 points, PGA score ≥3 points	266	128	44.8 ± 12.7	MSB 11022 at 80 mg ih in week 1, then 40 mg ih every 2 weeks	1–16 weeks	25.9 (11.0–86.0)	17.4 (12.0–61.8)	②⑥⑩⑪
		Control	BSA ≥10%, PASI ≥12 points, PGA score ≥3 points			42.4 ± 11.8	MSB 11022 at 80 mg ih in week 1, then 40 mg ih every 2 weeks		27.1 (10.0–72.0)	18.4 (12.1–48.2)
	2	1*	In the test group of stage 1, PASI-50 patients continued				MSB 11022 at 40 mg ih every 2 weeks	17–51 weeks
		2^#	In the control group of stage 1, PASI-50 patients were randomly assigned				Humira at 40 mg ih every 2 weeks
		3^Δ	In the control group of stage 1, PASI-50 patients were randomly assigned				MSB 11022 at 40 mg ih every 2 weeks
Papp 2017 [26]	1	Test	BSA ≥10%, PASI ≥12 points, PGA score in stage 1 ≥ 3 points	228	122	46 (35–54)	ABP 501 at 80 mg ih in week 1, then 40 mg ih every 2 weeks	1–16 weeks	20 (15–32)	17.1 (13.8–22.7)	①②③④⑤⑥⑦⑧⑨⑩
		Control	BSA ≥10%, PASI ≥12 points, PGA score in stage 1 ≥ 3 points			41 (33–56)	Humira 80 mg ih in week 1, then 40 mg ih every 2 weeks		23 (15–40)	18.3 (14.4–24.7)
Papp 2017 [27]	2	1*	In the test group of stage 1, PASI-50 patients continued	204	104	46 (35–54)	ABP 501 at 40 mg ih every 2 weeks	17–52 weeks	20.0 (14.0–30.0)	16.9 (13.8–21.9)	①②③④⑤⑥⑦⑨
		2^#	In the control group of stage 1, PASI-50 patients were randomly assigned			39 (30–57)	Humira at 40 mg ih every 2 weeks		25.0 (15.0–42.0)	18.5 (14.7–24.9)
		3^Δ	In the control group of stage 1, PASI-50 patients were randomly assigned			46 (36–57)	ABP 501 at 40 mg ih every 2 weeks		25.0 (16.0–38.0)	18.8 (14.7–25.5)
Samtsov 2022 [28]	1	Test	BSA ≥10%, PASI ≥12 points, PGA score ≥3 points	227	119	42.5 (34–50)	BCD-057 at 80 mg ih in week 1, then 40 mg ih every 2 weeks	1–16 weeks	32.5 (18–54.1)	23.3 (17.4–35.1)	②⑤⑥⑦⑧⑩⑪
		Control	BSA ≥10%, PASI ≥12 points, PGA score ≥3 points			42.5 (32–52)	Humira at 80 mg ih in week 1, then 40 mg ih every 2 weeks		33 (22–51)	24.15 (19.3–35.3)
	2	1*	Phase-1 trial group continued				BCD-057 at 40 mg ih every 2 weeks	25–51 weeks
		2^#	Random assignment of the control group in phase 1				Humira at 40 mg ih every 2 weeks
		3^Δ	Random assignment of the control group in phase 1				BCD-057 at 40 mg ih every 2 weeks
Blauvelt 2018 [29]	1	Test	BSA ≥10%, PASI ≥12 points, PGA score ≥3 points	465 in total	45.6 (18–81)	GP 2017 at 80 mg ih in week 1, then 40 mg ih every 2 weeks	1–16 weeks		19.9 (12.0–58.8)
		Control	BSA ≥10%, PASI ≥12 points, PGA score ≥3 points			46.9 (18–84)	Humira at 80 mg ih in week 1, then 40 mg ih every 2 weeks			20.2 (11.7–53.4)
	2	1^a	In the test group of stage 1, PASI-50 patients continued			46.2 (18–81)	GP 2017 at 40 mg ih every 2 weeks	17–51 weeks		20.6 (12.0–53.7)	②⑤⑥⑩⑪
		2^b	In the control group of stage 1, PASI-50 patients continued			48.0 (18–76)	Humira at 40 mg ih every 2 weeks			20.8(11.7–53.4)
		4^c	In the test group of stage 1, PASI-50 patients were randomly assigned			47.0 (21–79)	In the order of Humira, GP 2017 and Humira for 6 weeks each, at 40 mg ih every 2 weeks			19.1 (12.0–44.8)
		5^d	In the control group of stage 1, PASI-50 patients were randomly assigned			47.6 (19–80)	In the order of GP 2017, Humira and GP 2017 for 6 weeks each, at 40 mg ih every 2 weeks			19.7 (12.0–39.2)

Data are mean ± standard-deviation or median (interquartile range) values.

Notes: ^aGroup 1: biosimilars were injected in stages 1 and 2;

^b Group 2: reference agents were injected in stages 1 and 2; Group 3: reference agents were injected in stage 1 and biosimilars were injected in stage 2;

^c Group 4: biosimilars were injected in stage 1, and in stage 2 each drug was injected in the following order for 6 weeks: brand-name drug→biosimilar→brand-name drug;

^d Group 5: reference agents were injected in stage 1, and in stage 2 each drug was injected in the following order for 6 weeks: biosimilar→brand-name drug→biosimilar; ih: subcutaneous injection; BSA: body surface area; PGA: physicians’ global assessment.

Figure 4. Forest plots of PASI 50, PASI 75, PASI 90 and PASI 100 values for adalimumab use in patients with psoriasis.

Figure 5. Forest plots of safety indicators for 16 weeks of adalimumab use in patients with psoriasis.

Figure 6. Forest plots of safety indicators for 1–24 weeks of adalimumab use in patients with psoriasis.

Figure 7. Forest plots of safety indicators of adalimumab in patients with psoriasis at 1–51 weeks.

Figure 8. Funnel plots of outcome indicators.

Cai L, Li LF, Cheng H, et al. Efficacy and safety of HLX03, an adalimumab biosimilar, in patients with moderate-to-severe plaque psoriasis: a randomized, double-blind, phase III study. Adv Ther. 2022;39(1):583–597. doi: 10.1007/s12325-021-01899-0.

 PubMed Web of Science ®Google Scholar

Feldman SR, Reznichenko N, Pulka G, et al. Efficacy, safety and immunogenicity of AVT02 versus originator adalimumab in subjects with moderate to severe chronic plaque psoriasis: a multicentre, double-blind, randomised, parallel group, active control, phase III study.BioDrugs. 2021;35(6):735–748. doi: 10.1007/s40259-021-00502-w.

 PubMed Web of Science ®Google Scholar

Menter A, Arenberger P, Balser S, et al. Similar efficacy, safety, and immunogenicity of the biosimilar BI 695501 and adalimumab reference product in patients with moderate-to-severe chronic plaque psoriasis: results from the randomized phase III VOLTAIRE-PSO study. Expert Opin Biol Ther. 2021;21(1):87–96. doi: 10.1080/14712598.2021.1851362.

 PubMed Web of Science ®Google Scholar

Hercogova J, Papp KA, Chyrok V, et al. AURIEL-PsO: a randomized, double-blind phase III equivalence trial to demonstrate the clinical similarity of the proposed biosimilar MSB11022 to reference adalimumab in patients with moderate-to-severe chronic plaque-type psoriasis. Br J Dermatol. 2020;182(2):316–326. doi: 10.1111/bjd.18220.

 PubMed Web of Science ®Google Scholar

Papp K, Bachelez H, Costanzo A, et al. Clinical similarity of biosimilar ABP 501 to adalimumab in the treatment of patients with moderate to severe plaque psoriasis: a randomized, double-blind, multicenter, phase III study. J Am Acad Dermatol. 2017;76(6):1093–1102. doi: 10.1016/j.jaad.2016.12.014.

 PubMed Web of Science ®Google Scholar

Papp K, Bachelez H, Costanzo A, et al. Clinical similarity of the biosimilar ABP 501 compared with adalimumab after single transition: long-term results from a randomized controlled, double-blind, 52-week, phase III trial in patients with moderate-to-severe plaque psoriasis. Br J Dermatol. 2017;177(6):1562–1574. doi: 10.1111/bjd.15857.

 PubMed Web of Science ®Google Scholar

Samtsov AV, Bakulev AL, Khairutdinov VR, et al. Long-term data on the proposed adalimumab biosimilar BCD-057 in patients with moderate to severe psoriasis: a randomized controlled trial. PLoS One. 2022;17(2):e0263214. doi: 10.1371/journal.pone.0263214.

 PubMed Web of Science ®Google Scholar

Blauvelt A, Lacour JP, Fowler JF, et al. Phase III randomized study of the proposed adalimumab biosimilar GP2017 in psoriasis: impact of multiple switches. Br J Dermatol. 2018;179(3):623–631. doi: 10.1111/bjd.16890.

 PubMed Web of Science ®Google Scholar

Data availability statement

The data that support the findings of this study are stored in the First Affiliated Hospital of Xi’an Jiaotong University (Xi’an, China), and available from the corresponding author on reasonable request.