Certolizumab pegol in treatment of moderate to severe plaque psoriasis: effectiveness and safety compared to placebo
Näytönastekatsaukset
15.6.2020
Level of evidence: B
Certolizumab treatment, when compared to placebo, seems to increase the proportion of patients with moderate to severe plaque psoriasis to achieve a clinically meaningful improvement at 16 weeks of treatment. There may be more adverse events in certolizumab pegol treatment compared to placebo after 16 weeks of treatment. Most of them are mild upper respiratory infections.
The evidence is based on 3 RCTs. The evidence is downgraded due to imprecision.
| Reference | Study type | Population | Intervention and comparison | Outcomes | Risk of bias «Certolizumab pegol in treatment of moderate to severe plaque psoriasis: effectiveness and safety compared to placebo»1 |
|---|---|---|---|---|---|
| RCT=randomized controlled trial; PGA=Physician's Global Assessment, CZP= certolizumab pegol, s.c.=subcutaneous treatment, DLQI= Dermatology Life Quality Index | |||||
| «Gottlieb AB, Blauvelt A, Thaçi D ym. Certolizumab pegol for the treatment of chronic plaque psoriasis: Results through 48 weeks from 2 phase 3, multicenter, randomized, double-blinded, placebo-control»1 | pooled analysis of 2 RCTs | Adult patients (>18 years of age) from North America and Europe with moderate to severe plaque psoriasis. N=461 | CZP 400 mg s.c. every2 weeks (n=175), CZP 200 mg every 2 weeks (after loading dose of CZP 400 mg at weeks 0, 2, and 4) (n=186), or placeboevery 2 weeks (n=100) | Primary at 16 weeks PASI 75 and PGA 0/1.Secondary PASI 90, change in DLQI atweek 16 | After 16 weeks the randomization was dissolved |
| «Lebwohl M, Blauvelt A, Paul C ym. Certolizumab pegol for the treatment of chronic plaque psoriasis: Results through 48 weeks of a phase 3, multicenter, randomized, double-blind, etanercept- and placeb»2 | RCT | Adult patients (>18 years of age) from North America and Europe with moderate to severe plaque psoriasis. N=461 | CZP 400 mg s.c. every2 weeks (n=175), CZP 200 mg every 2 weeks (after loading dose of CZP 400 mg at weeks 0, 2, and 4) (n=186), or placeboevery 2 weeks (n=100) | Primary PASI 75 CZP (any dose) vs placebo at 12 weeks.Secondary PASI75 at week 16; PGA0/1 atweeks 12 and 16; PASI 90 atweeks 12 and 16 | Randomization |
Results
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect (95% CI) |
|---|---|---|---|---|---|
| I= intervention; C=comparison; CI=confidence interval, PGA=Physician's Global Assessment, CZP= certolizumab pegol | |||||
| «Gottlieb AB, Blauvelt A, Thaçi D ym. Certolizumab pegol for the treatment of chronic plaque psoriasis: Results through 48 weeks from 2 phase 3, multicenter, randomized, double-blinded, placebo-control»1 | 2 RCTs CZP 400 n=175 CZP 200 n=186 Placebo n=100 | 16 weeks | (65.3) (56.8) | (2.7) | OR CZP 400 vs. placebo 69.5 (16.5 to 292.0) CZP 200 vs. placebo 48.7 (11.7 to 203.3) |
| «Lebwohl M, Blauvelt A, Paul C ym. Certolizumab pegol for the treatment of chronic plaque psoriasis: Results through 48 weeks of a phase 3, multicenter, randomized, double-blind, etanercept- and placeb»2 | 1 RCT CZP 400 n=167 CZP 200 n=165 Placebo n=157 | Week 16 | (58.4) (48.3) | (3.4) | OR CZP 400 vs. placebo 40.7 (9.7 to 170.2) CZP 200 vs. placebo 27.2 (6.5 to 113.5) |
| Level of evidence: moderate The quality of evidence is downgraded due to imprecision. | |||||
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect (95% CI) |
|---|---|---|---|---|---|
| I= intervention; C=comparison; CI=confidence interval, CZP= certolizumab pegol | |||||
| «Gottlieb AB, Blauvelt A, Thaçi D ym. Certolizumab pegol for the treatment of chronic plaque psoriasis: Results through 48 weeks from 2 phase 3, multicenter, randomized, double-blinded, placebo-control»1 | 2 RCTs CZP 400 n=175 CZP 200 n=186 Placebo n=100 | 16 weeks | (52.2)(45.9) | (2.5) | OR CZP 400 vs. placebo 44.1 (8.6 to 226.5) CZP 200 vs. placebo 34.3 (6.7 to 175.7) |
| «Lebwohl M, Blauvelt A, Paul C ym. Certolizumab pegol for the treatment of chronic plaque psoriasis: Results through 48 weeks of a phase 3, multicenter, randomized, double-blind, etanercept- and placeb»2 | 1 RCT CZP 400 n=167 CZP 200 n=165 Placebo n=157 | 16 weeks | (49.1)(39.8) | (0.3) | OR CZP 400 vs. placebo 72.3 (14.7 to 356.6) CZP 200 vs. placebo 49.5 (10.0 to 245.3) |
| Level of evidence: moderate The quality of evidence is downgraded due to indirectness (secondary outcome) and imprecision (wide CIs). | |||||
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect (95% CI) |
|---|---|---|---|---|---|
| «Gottlieb AB, Blauvelt A, Thaçi D ym. Certolizumab pegol for the treatment of chronic plaque psoriasis: Results through 48 weeks from 2 phase 3, multicenter, randomized, double-blinded, placebo-control»1 | 2 RCTs CZP 400 n=175 CZP 200 n=186 Placebo n=100 | 16 weeks | All 117 (67) 106 (57) Serious 9 (5) 4 (2) | All 61 (61) Serious 1 (1) | NA |
| «Lebwohl M, Blauvelt A, Paul C ym. Certolizumab pegol for the treatment of chronic plaque psoriasis: Results through 48 weeks of a phase 3, multicenter, randomized, double-blind, etanercept- and placeb»2 | 1 RCT CZP 400 n=167 CZP 200 n=165 Placebo n=157 | 12 weeks | All 82 (49.1) 78 (47.3) Serious 4 (2.4) 1 (0.6) | All 32 (56.1) Serious 5 (8.8) | NA |
| Level of evidence: low The quality of evidence is downgraded due to indirectness (short follow-up time) and imprecision. | |||||
References
- Gottlieb AB, Blauvelt A, Thaçi D ym. Certolizumab pegol for the treatment of chronic plaque psoriasis: Results through 48 weeks from 2 phase 3, multicenter, randomized, double-blinded, placebo-controlled studies (CIMPASI-1 and CIMPASI-2). J Am Acad Dermatol 2018;79:302-314.e6 «PMID: 29660421»PubMed
- Lebwohl M, Blauvelt A, Paul C ym. Certolizumab pegol for the treatment of chronic plaque psoriasis: Results through 48 weeks of a phase 3, multicenter, randomized, double-blind, etanercept- and placebo-controlled study (CIMPACT). J Am Acad Dermatol 2018;79:266-276.e5 «PMID: 29660425»PubMed