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.
Ref. | Study type | Population | Intervention and comparison | Outcomes | Risk of bias |
---|---|---|---|---|---|
RCT=randomized controlled trial; SR=systematic review; MA=meta-analysis | |||||
«Mease PJ, van der Heijde D, Ritchlin CT ym. Ixekiz...»1 | RCT | 417 (103/107/101/106) TNF-inhibitor naïve adult patients with active psoriatic arthritis | Ixekizumab 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 ...»2 | RCT | 363 (123/122/118) adult patients with active psoriatic arthritis and an inadequate response to TNF-inhibitors | Ixekizumab 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 ...»3 | RCT | 566 (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, rando...»4 | RCT | 566 (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) |
Reference | Comments |
---|---|
«Mease PJ, van der Heijde D, Ritchlin CT ym. Ixekiz...»1 | Study was funded by Eli Lilly. |
«Nash P, Kirkham B, Okada M ym. Ixekizumab for the ...»2 | Study was funded and data analyzed by Eli Lilly. |
«Mease PJ, Smolen JS, Behrens F ym. A head-to-head ...»3 | Study 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, rando...»4 | Study was funded by Eli Lilly, which also contributed to study design, data collection, data analysis, data interpretation, manuscript preparation and publication decisions. |
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 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. Ixekiz...»1 | 417 (103/107/101/106) |
24 weeks | IXEQ2W: 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 ...»2 | 363 (123/122/118) |
24 weeks | IXEQ2W: 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 |
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 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. Ixekiz...»1 | 417 (103/107/101/106) | 12 weeks | IXEQ2W: 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 ...»2 | 363 (123/122/118) |
12 weeks | IXEQ2W: 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 |
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 vs. control (95% CI) |
---|---|---|---|---|---|
«Mease PJ, Smolen JS, Behrens F ym. A head-to-head ...»3 | 566 (283/283) | 24 weeks | ACR50+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, rando...»4 | 566 (283/283) | 52 weeks | ACR50+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 |
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, IXEQ2W=Ixekizumab 80mg every 2 weeks, IXEQ4W=Ixekizumab 80mg every 4 weeks; ADA=adalimumab | |||||
«Mease PJ, van der Heijde D, Ritchlin CT ym. Ixekiz...»1 | 417 | 24 weeks | IXEQ2W: 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 ...»2 | 363 | 24 weeks | IXEQW2: 90 (73) IXEQW4: 83 (68) |
76 (64) | |
Level of evidence: low (imprecision) |
Other endpoints
Study 1:
Study 2: