Takaisin

Secukinumab treatment in patients with active psoriatic arthritis: effectiveness and safety compared to placebo.

Näytönastekatsaukset
Krista Nuotio
10.11.2021

Level of evidence: A

Subcutaneous secukinumab treatment at the dose of 150-300 mg monthly increases the proportion of patients with psoriatic arthritis achieving the ACR20 response at week 24 when compared to placebo (approximately 42–63 % vs. 15–27 %), and it is safe.

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.

Table 1. Description of the included studies
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
Table 2. Additional comments for included studies
Reference Comments
«Mease PJ, McInnes IB, Kirkham B ym. Secukinumab In...»1
  • First 4 weeks intravenous administration, whereafter subcutaneous administration.
  • Re-randomization of placebo-treated patients at week 16 or 24 depending on the response.
  • In the efficacy analyses, the placebo-controlled period included data through week 24, with imputation for patients who switched to active treatment at week 16. In the safety analyses, the placebo-controlled period included data only through week 16, when patients received the originally assigned study medication.
«McInnes IB, Mease PJ, Kirkham B ym. Secukinumab, a...»2
  • Re-randomization of placebo-treated patients at week 16 or 24 depending on the response.
  • Study was funded by Novartis.
«Nash P, Mease PJ, McInnes IB ym. Efficacy and safe...»3
  • Re-randomization of placebo-treated patients at week 16 or 24 depending on the response.
  • Study was funded by Novartis Pharma.
«Mease P, van der Heijde D, Landewé R ym. Secukinum...»4
  • Study was funded by Novartis.
«Baraliakos X, Gossec L, Pournara E ym. Secukinumab...»5
  • Primary outcome differs from other studies.
  • At week 12 patients were re-randomized to SEC 300mg or SEC 150mg until week 52.

Results

Table 3. ACR20 response at weeks 12–24
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
Table 4. ACR50 response at weeks 12–24
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
Table 5. ACR70 response at weeks 12–24
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
Table 6. All adverse events at weeks 12–24
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

References

  1. Mease PJ, McInnes IB, Kirkham B ym. Secukinumab Inhibition of Interleukin-17A in Patients with Psoriatic Arthritis. N Engl J Med 2015;373:1329-39 «PMID: 26422723»PubMed
  2. McInnes IB, Mease PJ, Kirkham B ym. Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2015;386:1137-46 «PMID: 26135703»PubMed
  3. Nash P, Mease PJ, McInnes IB ym. Efficacy and safety of secukinumab administration by autoinjector in patients with psoriatic arthritis: results from a randomized, placebo-controlled trial (FUTURE 3). Arthritis Res Ther 2018;20:47 «PMID: 29544534»PubMed
  4. Mease P, van der Heijde D, Landewé R ym. Secukinumab improves active psoriatic arthritis symptoms and inhibits radiographic progression: primary results from the randomised, double-blind, phase III FUTURE 5 study. Ann Rheum Dis 2018;77:890-897 «PMID: 29550766»PubMed
  5. Baraliakos X, Gossec L, Pournara E ym. Secukinumab in patients with psoriatic arthritis and axial manifestations: results from the double-blind, randomised, phase 3 MAXIMISE trial. Ann Rheum Dis 2021;80:582-590 «PMID: 33334727»PubMed