Näytönastekatsaukset

Ixekizumab treatment in patients with active psoriatic arthritis: effectiveness compared to placebo and adalimumab

Näytönastekatsaukset
10.11.2021
Jorma Komulainen

Level of evidence: A

Ixekizumab treatment at the dose of 80 mg, when compared to placebo, increases the proportion of patients with active psoriatic arthritis achieving the ACR20 response at week 24 and probably already at week 12.

This is true also for ACR50 and ACR70 response rates (data not shown here). There seems to be no clinically relevant differences in efficacy between 2-week interval and 4-week interval dosing regimens. However, treatment seems to have more adverse events than placebo. The efficacy of ixekizumab and adalimumab may be equal, when measured with the ACR50 response at weeks 24 and 52.

Table 1. Description of the included studies
Ref.Study typePopulationIntervention and comparisonOutcomesRisk of bias
RCT=randomized controlled trial; SR=systematic review; MA=meta-analysis
«Mease PJ, van der Heijde D, Ritchlin CT ym. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the »1RCT417 (103/107/101/106) TNF-inhibitor naïve adult patients with active psoriatic arthritisIxekizumab 80mg every 2 weeks (IXEQ2W); Ixekizumab 80mg every 2 weeks (IXEQ4W);
Adalimumab 40mg Q2W;
placebo		Primary: ACR20 at week 24;
Secondary: ACR20 at week 12, ACR50 at week 12/24, ACR70 at week 12/24, adverse events		Low
«Nash P, Kirkham B, Okada M ym. Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week random»2RCT363 (123/122/118) adult patients with active psoriatic arthritis and an inadequate response to TNF-inhibitorsIxekizumab 80mg every 2 weeks (IXEQ2W); Ixekizumab 80mg every 2 weeks (IXEQ2W);
placebo		Primary: ACR20 at week 24;
Secondary: ACR20 at week 12, ACR50 at week 12/24, ACR70 at week 12/24, adverse events		Low
«Mease PJ, Smolen JS, Behrens F ym. A head-to-head comparison of the efficacy and safety of ixekizumab and adalimumab in biological-naïve patients with active psoriatic arthritis: 24-week results of a »3RCT566 (283/283) adult patients with psoriatic arthritis and naïve to biological disease-modifying antirheumatic drug.Ixekizumab s.c. 160 mg starting dose followed by 80 mg every 4 weeks or 2 weeks (moderate to severe psoriasis).
Adalimumab s.c. 40 mg starting dose followed by 40 mg every 2 weeks, or 80 mg starting dose followed by 40 mg every 2 weeks starting at week 1 (moderate to severe psoriasis)		Primary: Simultaneous achievement of ACR50 and PASI100 at week 24.
Secondary: ACR50 at week 24.		Moderate (only assessors were blinded)
«Smolen JS, Mease P, Tahir H ym. Multicentre, randomised, open-label, parallel-group study evaluating the efficacy and safety of ixekizumab versus adalimumab in patients with psoriatic arthritis naïve »4RCT566 (283/283) adult patients with psoriatic arthritis and naïve to biological disease-modifying antirheumatic drug.Ixekizumab s.c 160 mg starting dose followed by 80 mg every 4 or 2 weeks (moderate to severe psoriasis). Adalimumab s.c. 40 mg starting dose followed by 40 mg every 2 weeks, or 80 mg starting dose followed by 40 mg every 2 weeks starting at week 1 (moderate to severe psoriasis)The proportion
of patients achieving simultaneous ACR50 and PASI100
responses at week 52.		Moderate (only assessors were blinded)
Table 2. Additional comments for included studies
ReferenceComments
«Mease PJ, van der Heijde D, Ritchlin CT ym. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the »1Study was funded by Eli Lilly.
«Nash P, Kirkham B, Okada M ym. Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week random»2Study was funded and data analyzed by Eli Lilly.
«Mease PJ, Smolen JS, Behrens F ym. A head-to-head comparison of the efficacy and safety of ixekizumab and adalimumab in biological-naïve patients with active psoriatic arthritis: 24-week results of a »3Study was funded by Eli Lilly, which also contributed to study design, data collection, data analysis, data interpretation, manuscript preparation and publication decisions.
«Smolen JS, Mease P, Tahir H ym. Multicentre, randomised, open-label, parallel-group study evaluating the efficacy and safety of ixekizumab versus adalimumab in patients with psoriatic arthritis naïve »4Study was funded by Eli Lilly, which also contributed to study design, data collection, data analysis, data interpretation, manuscript preparation and publication decisions.

Results

Table 3. ACR20 at week 24
ReferenceNumber of studies and number of patients (I/C)Follow-up timeAbsolute number of events (%) IAbsolute number of events (%) CAbsolute difference vs. placebo (95% CI)
I=intervention; C=comparison; CI=confidence interval, IXEQ2W=Ixekizumab 80mg every 2 weeks, IXEQ4W=Ixekizumab 80mg every 4 weeks; ADA=adalimumab
*= p≤0.001, 95% CI not given
«Mease PJ, van der Heijde D, Ritchlin CT ym. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the »1417
(103/107/101/106) 		24 weeksIXEQ2W: 64 (62.1)
IXEQ4W: 62 (57.9)		ADA: 58 (57.4)
Placebo: 32 (30.2)		IXEQ2W 31.9 % *
IXEQ4W 27.7 % *
«Nash P, Kirkham B, Okada M ym. Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week random»2363
(123/122/118)		24 weeksIXEQ2W: 59 (48)
IXEQ4W: 65 (53)		Placebo: 23 (19)IXEQ2W 28.5 % (17.1–39.8)
IXEQ4W 33.8 % (22.4–45.2)
Level of evidence: high
Table 4. ACR20 at week 12. The ACR20 response at 12 weeks was tested as a secondary end point.
ReferenceNumber of studies and number of patients (I/C)Follow-up timeAbsolute number of events (%) IAbsolute number of events (%) CAbsolute difference vs. placebo (95% CI)
I= intervention; C=comparison; CI=confidence interval, IXEQ2W=Ixekizumab 80mg every 2 weeks, IXEQ4W=Ixekizumab 80mg every 4 weeks; ADA=adalimumab
*= p≤0.001, 95% CI not given
«Mease PJ, van der Heijde D, Ritchlin CT ym. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the »1 417 (103/107/101/106)12 weeksIXEQ2W: 64 (60.2)
IXEQ4W: 61 (57.0)		ADA: 52 (51.5)
Placebo: 33 (31.1)		IXEQ2W 29.1 % *
IXEQ4W 25.9 % *
«Nash P, Kirkham B, Okada M ym. Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week random»2363
(123/122/118)		12 weeksIXEQ2W: 59 (48.0)
IXEQ4W: 61 (50.0)		Placebo: 26 (22.0)IXEQ2W 25.9 % (14.4–37.5)
IXEQ4W 28.0 % (16.4–40.0)
Level of evidence: high
Table 5. ACR50 with PASI100 and ACR50 at week 24 and 52
ReferenceNumber of studies and number of patients (I/C)Follow-up timeAbsolute number of events (%) IAbsolute number of events (%) CAbsolute difference vs. control (95% CI)
«Mease PJ, Smolen JS, Behrens F ym. A head-to-head comparison of the efficacy and safety of ixekizumab and adalimumab in biological-naïve patients with active psoriatic arthritis: 24-week results of a »3566 (283/283)24 weeksACR50+PASI100:
102/283 (36.0 %, 95 %CI 30.4–41.6)
ACR50:
143/283 (50.5 %, 95 %CI 44.7–56.4)		ACR50+PASI100:
79/283 (27.9 %, 95 %CI 22.7–33.1)
ACR50:
132/283 (46.6 %, 95 %CI 40.8–52.5)		8.1 % (0.5–15.8 %)
3.9 % (-4.3–12.1 %)
«Smolen JS, Mease P, Tahir H ym. Multicentre, randomised, open-label, parallel-group study evaluating the efficacy and safety of ixekizumab versus adalimumab in patients with psoriatic arthritis naïve »4566 (283/283)52 weeksACR50+PASI100:
111/283 (39.2 %, 95 %CI 33.5–44.9)
ACR50:
141/283 (49.8 %, 95 %CI 44.0–55.6)		ACR50+PASI100:
74/283 (26.1 %, 95 %CI 21.0–31.3)
ACR50:
141/283 (49.8 %, 95 %CI 44.0–55.6)		13.1 % (5.4–20.7 %)
0.0 (-8.2–8.2)
Level of evidence: low, due to risk of bias and imprecision
Table 6. Adverse events
ReferenceNumber of studies and number of patients (I/C)Follow-up timeAbsolute number of events (%) IAbsolute number of events (%) CRelative effect (95% CI)
I= intervention; C=comparison; CI=confidence interval, IXEQ2W=Ixekizumab 80mg every 2 weeks, IXEQ4W=Ixekizumab 80mg every 4 weeks; ADA=adalimumab
«Mease PJ, van der Heijde D, Ritchlin CT ym. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the »141724 weeksIXEQ2W: 67 (65.7)
IXEQ4W: 71 (66.4)		ADA: 65 (64.4)
Placebo 50 (47.2)
«Nash P, Kirkham B, Okada M ym. Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week random»236324 weeksIXEQW2: 90 (73)
IXEQW4: 83 (68)		76 (64)
Level of evidence: low (imprecision)

Other endpoints

Study 1:

  • ACR50 at week 24: IXEQ2W 46.6 % *, IXEQ4W 40.2 % *, ADA 29.7 % *, PLAC 15.1%; *= p<0.001 against placebo
  • ACR70 at week 24: IXEQ2W 34.0 % *, IXEQ4W 23.4 % *, ADA 25.7 % *, PLAC 5.7%; *= p<0.001 against placebo.

Study 2:

  • ACR50 at week 24: IXEQ2W 33 % *, IXEQ4W 35 % *, PLAC 5 %; *= p<0.0001 against placebo
  • ACR70 at wee 24: IXEQ2W 12 % *, IXEQ4W 22 % *, PLAC 0 %; *=p<0.0001 against placebo.

References

  1. Mease PJ, van der Heijde D, Ritchlin CT ym. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Ann Rheum Dis 2017;76:79-87 «PMID: 27553214»PubMed
  2. Nash P, Kirkham B, Okada M ym. Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial. Lancet 2017;389:2317-2327 «PMID: 28551073»PubMed
  3. Mease PJ, Smolen JS, Behrens F ym. A head-to-head comparison of the efficacy and safety of ixekizumab and adalimumab in biological-naïve patients with active psoriatic arthritis: 24-week results of a randomised, open-label, blinded-assessor trial. Ann Rheum Dis 2020;79:123-131 «PMID: 31563894»PubMed
  4. Smolen JS, Mease P, Tahir H ym. Multicentre, randomised, open-label, parallel-group study evaluating the efficacy and safety of ixekizumab versus adalimumab in patients with psoriatic arthritis naïve to biological disease-modifying antirheumatic drug: final results by week 52. Ann Rheum Dis 2020;79:1310-1319 «PMID: 32660977»PubMed