The results may be achieved already at weeks 12–16. Significantly higher ACR50 and ACR70 response rates for both doses were observed for secukinumab compared to placebo as well, but it was observed more slowly. Mostly secukinumab provided sustained improvements in signs and symptoms in active PsA patients through 52 weeks. The safety profile was consistent with that reported previously. The quality and the applicability of the evidence is good.
Reference | Study type | Population | Intervention and comparison | Outcomes | Risk of bias |
---|---|---|---|---|---|
«Mease PJ, McInnes IB, Kirkham B ym. Secukinumab In...»1 | RCT, double-blind pbo-controlled phase III multicenter study. (FUTURE 1) |
606 pts ≥ 18 yrs with active PsA, (≥ 3 tender joints and ≥ 3 swollen joints, despite previous treatment with NSAID, dMARDs, or TNF inhibitors. The concomitant use of oral glucocorticoids and methotrexate was permitted, provided that the dose was stable. |
10mg/kg SEC i.v. at weeks 0, 2 and 4, followed by either SEC 150 mg, SEC 75 mg or
placebo s.c. every 4 weeks Re-randomization at week 16 for patients having placebo. |
Primary: ACR20 response at week 24 Secondary: PASI 75 and PASI 90, DAS28-CRP, QoL (SF-36), HAQ-DI, ACR50 and radiographic progression at week 24. |
Low Re-randomization at week 16 may affect results at week 24. |
«McInnes IB, Mease PJ, Kirkham B ym. Secukinumab, a...»2 | RCT, double-blind pbo-controlled phase III multicenter study. (FUTURE 2) |
397 pts ≥ 18 yrs with active PsA, (≥ 3 tender joints and ≥ 3 swollen joints, despite previous treatment with NSAID, dMARDs, or TNF inhibitors. The concomitant use of oral glucocorticoids and methotrexate was permitted, provided that the dose was stable. |
SEC 300mg, 150mg, 75mg or pbo s.c at weeks 0, 2 and 4, and every 4 weeks thereafter Re-randomization at week 16 for patients having placebo. |
Primary: ACR20 response at week 24 Secondary: PASI 75 and PASI 90, DAS28-CRP, QoL (SF-36), HAQ-DI, ACR50 and ACR70. |
Low Re-randomization at week 16 may affect results at week 24. |
«Nash P, Mease PJ, McInnes IB ym. Efficacy and safe...»3 | RCT, multicenter double-blind pbo-controlled study. (FUTURE 3) | 414 pts with active PsA despite previous treatment with NSAIDs, DMARDS, or anti-TNF agents. Patients treated with up to three anti-TNF agents could enroll if they had an inadequate response for at least 3 months or had stopped anti-TNF therapy due to safety/tolerability reasons (anti-TNF-IR), and had an appropriate washout period before randomization. Concomitant use of oral corticosteroids and methotrexate was allowed if the dose was stable for at least 2 weeks and 4 weeks before randomization, respectively. S.c. secukinumab self-administration with an autoinjector. |
SEC 300mg, SEC 150mg or pbo s.c at weeks 0, 2 and 4, and every 4 weeks thereafter Re-randomization at week 16 or 24 for patients having placebo. |
Primary: ACR20 response at week 24 Secondary: ACR50, DAS28-CRP, PASI 75, SF-36, PASI 90, HAQ-DI, FACIT, VAS and autoinjector usability. |
Low Re-randomization at week 16 or 24, may affect final results. |
«Mease P, van der Heijde D, Landewé R ym. Secukinum...»4 | RCT, double-blind pbo-controlled phase 3, multicenter study. (FUTURE 5) |
Adults (n=996) with active PsA. corticosteroids, NSAIDs and methotrexate were allowed, provided the dose was stable and remained so for the first 24 weeks of the study. | SEC 300 mg with loading dose (LD) (n=222), SEC 150 mg with LD (n=220), SEC 150 mg without LD (n=222) or placebo (n=332). | Primary: ACR20 response at week 16. Secondary: Radiographic structural progression at week 24. PASI75, PASI90, ACR50, HAQ-DI, DAS28-CRP and resolution of enthesitis and dactylitis at week 16. |
Low |
«Baraliakos X, Gossec L, Pournara E ym. Secukinumab...»5 | RCT, double-blind pbo-controlled phase 3b multicenter study. MAXIMISE trial (NCT02721966) |
498 pts ≥ 18 yrs with PsA and classified by CASPAR criteria with spinal pain VAS ≥ 40/100 and BASDAI score ≥ 4 despite use of at least 2 NSAIDs. | SEC 300mg s.c. (n=167) or SEC 150mg s.c. (n=165) with a weekly dose up to week 4 and
every 4 weeks thereafter until 12 weeks vs. PBO s.c. (n=166). At week 12 pbo pts were re-randomized to SEC 300mg or SEC 150mg until week 52. |
Primary: ASAS20 response at week 12. Secondary: ASAS40, BASDAI50, ACR20, mean change from baseline in spinal pain measured by VAS, HAQ-DI, FACIT and ASAS Health Index at week 12. |
Low |
RCT=randomized controlled trial; SR=systematic review; MA=meta-analysis, pts=patients, PsA=Psoriatic arthritis, VAS=visual analogue score, CASPAR= ClASsification criteria for Psoriatic Arthritis, BASDAI=Bath Ankylosing Spondylitis Disease Activity Index, SEC= secukinumab, PBO= placebo, LD=loading dose, ASAS20=Assessment of SpondyloArthritis international Society, HAQ-DI=Health Assessment Questionnaire Disability Index score, FACIT=Functional Assessment of Chronic Illness Therapy -fatigue scale |
Reference | Comments |
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«Mease PJ, McInnes IB, Kirkham B ym. Secukinumab In...»1 |
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«McInnes IB, Mease PJ, Kirkham B ym. Secukinumab, a...»2 |
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«Nash P, Mease PJ, McInnes IB ym. Efficacy and safe...»3 |
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«Mease P, van der Heijde D, Landewé R ym. Secukinum...»4 |
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«Baraliakos X, Gossec L, Pournara E ym. Secukinumab...»5 |
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Results
Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Absolute difference (95% CI) |
---|---|---|---|---|---|
I=intervention; C=comparison; CI=confidence interval, SEC= secukinumab, PBO= placebo, NA=not applicable | |||||
«Mease PJ, McInnes IB, Kirkham B ym. Secukinumab In...»1 | 606 pts (n=202 in every group) | 24 weeks, long-term efficacy and safety up to 52 weeks. | 150 mg SEC 50 % |
17.3% | 32.7 % (24–41) |
«McInnes IB, Mease PJ, Kirkham B ym. Secukinumab, a...»2 | 397 pts (n=100 SEC 300mg, n=100 SEC 150mg, n=99 SEC 75mg and n=98 pbo) | 24 weeks, long-term efficacy and safety up to 52 weeks. | 300 mg SEC 54 % 150 mg SEC 51 % |
15 % | 39 % (27–51) [OR 6.81 (3.42–13.56)] 36 % (24–48) [OR 6.52 (3.25–13.08)] |
«Nash P, Mease PJ, McInnes IB ym. Efficacy and safe...»3 | 414 pts (n=139 SEC 300mg, n=138 SEC 150mg, n=137 pbo) | 24 weeks, long-term efficacy and safety up to 52 weeks. | SEC 300mg 48.2 % SEC 150mg 42.0 % |
16.1 % | 32.1 % (22–42) 25.9 % (16–36) |
«Mease P, van der Heijde D, Landewé R ym. Secukinum...»4 | 996 pts (n=222 SEC 300mg with LD, n=220 SEC 150mg with LD, n=222 SEC 150mg without louding dose, n=332 pbo) | 16 weeks, radiological assessment at week 24. | SEC 300mg with LD 62.6 % SEC 150mg with LD 55.5 % SEC 150mg without LD 59.5 % |
27.4 % | 35.2 % (27–43) 28.1 % (20–36) 32.1 % (24–40) |
«Baraliakos X, Gossec L, Pournara E ym. Secukinumab...»5 | 498 pts (n=167 SEC 300mg, n=165 SEC 150mg, n=166 pbo) | 12 weeks, long-term efficacy and safety up to 52 weeks. | SEC 300mg 52 % SEC 150mg 57 % |
19 % | 33 % [OR 4.8 (2.8–8.2)] 38 % [OR 5.7 (3.3–10.0)] |
Level of evidence: high |
Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Absolute difference (95% CI) |
---|---|---|---|---|---|
I=intervention; C=comparison; CI=confidence interval, SEC= secukinumab, PBO= placebo, NA=not applicable | |||||
«Mease PJ, McInnes IB, Kirkham B ym. Secukinumab In...»1 | 606 pts (n=202 in every group) | 24 weeks, long-term efficacy and safety up to 52 weeks. | 150 mg SEC 34.7 % |
7.4 % | 27.3 % (20–35) |
«McInnes IB, Mease PJ, Kirkham B ym. Secukinumab, a...»2 | 397 pts (n=100 SEC 300mg, n=100 SEC 150mg, n=99 SEC 75mg and n=98 pbo) | 24 weeks, long-term efficacy and safety up to 52 weeks. | 300 mg SEC 35 % 150 mg SEC 35 % |
7 % | 28 % (17–39) [OR 7.15 (2.97–17.22)] 28 % (17–39) [OR 7–54 (3.11–18.25)] |
«Nash P, Mease PJ, McInnes IB ym. Efficacy and safe...»3 | 414 pts (n=139 SEC 300mg, n=138 SEC 150mg, n=137 pbo) | 24 weeks, long-term efficacy and safety up to 52 weeks. | SEC 300mg 34.5 % SEC 150mg 18.8 % |
8.8 % | 25.7 % (17-35) 10.0 % (2-18) |
«Mease P, van der Heijde D, Landewé R ym. Secukinum...»4 | 996 pts (n=222 SEC 300mg with LD, n=220 SEC 150mg with LD, n=222 SEC 150mg without louding dose, n=332 pbo) | 16 weeks, radiological assessment at week 24. | SEC 300mg with LD 39.6 % SEC 150mg with LD 35.9 % SEC 150mg without LD 32.0 % |
8.1 % | 31.5 % (24–39) 27.8 % (21–35) 23.9 % (17–31) |
Level of evidence: high |
Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Absolute difference (95% CI) |
---|---|---|---|---|---|
I=intervention; C=comparison; CI=confidence interval, SEC= secukinumab, PBO= placebo, NA=not applicable | |||||
«Mease PJ, McInnes IB, Kirkham B ym. Secukinumab In...»1 | 606 pts (n=202 in every group) | 24 weeks, long-term efficacy and safety up to 52 weeks. | 150 mg SEC 18.8 % |
2.0 % | 16.8 % (11–23) 14.8 % (9–20) |
«Mease P, van der Heijde D, Landewé R ym. Secukinum...»4 | 996 pts (n=222 SEC 300mg with LD, n=220 SEC 150mg with LD, n=222 SEC 150mg without louding dose, n=332 pbo) | 16 weeks, radiological assessment at week 24. | SEC 300mg with LD 20.3 % SEC 150mg with LD 18.2 % SEC 150mg without LD 14.9 % |
4.2 % | 16.1 % (10–22) 14.0 % (8–20) 10.7 % (5–16) |
Level of evidence: moderate |
Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Absolute difference (95% CI) |
---|---|---|---|---|---|
«Mease PJ, McInnes IB, Kirkham B ym. Secukinumab In...»1 | 606 pts (n=202 in every group) | 24 weeks, long-term efficacy and safety weeks 16 and 52. | 150 mg SEC 64.9 % 75 mg SEC 60.4 % |
58.4 % | |
«McInnes IB, Mease PJ, Kirkham B ym. Secukinumab, a...»2 | 397 pts (n=100 SEC 300mg, n=100 SEC 150mg, n=99 SEC 75mg and n=98 pbo) | 16 weeks | 150 mg SEC 56 % 150 mg SEC 57 % 75 mg SEC 48 % |
58 % | |
«Nash P, Mease PJ, McInnes IB ym. Efficacy and safe...»3 | 414 pts (n=139 SEC 300mg, n=138 SEC 150mg, n=137 pbo) | 16 weeks | SEC 300mg 54.7 % SEC 150mg 58.9 % |
56.2 % | |
«Mease P, van der Heijde D, Landewé R ym. Secukinum...»4 | 996 pts (n=222 SEC 300mg with LD, n=220 SEC 150mg with LD, n=222 SEC 150mg without louding dose, n=332 pbo) | 24 weeks | SEC 300mg with LD 63.1 % SEC 150mg with LD 62.7 % SEC 150mg without LD 61.3 % |
62.0 % | |
«Baraliakos X, Gossec L, Pournara E ym. Secukinumab...»5 | 498 pts (n=167 SEC 300mg, n=165 SEC 150mg, n=166 pbo) | 12 weeks | SEC 300mg 40.1 % SEC 150mg 37.0 % |
48.2 % | |
Level of evidence: high/moderate | |||||
I=intervention; C=comparison; CI=confidence interval, SEC= secukinumab, PBO= placebo, NA=not applicable |