Study | Population | RoB | Treatment | n | Primary endpoint | P value | ACR20 (%) | ACR50 (%) | ACR70 (%) | ΔmTSS | ΔHAQ-DI | Dactylitis resolution (%) | Enthesitis resolution (%) | PASI75 (%) |
IL-17A inhibitors | ||||||||||||||
Mease et al (SPIRIT-P1)1 | csDMARD-IR | Low | Placebo±csDMARD | 106 | ACR20 (week 24) | Ref | 30.2 | 15.1 | 5.7 | 0.49 | −0.18 | 25 | 19.3 | 10.4 |
IXE 80 mg Q4W±csDMARD | 107 | <0.001 | 57.9 | 40.2 | 23.4 | 0.17 | −0.44 | 79.5 | 42.6 | 71.2 | ||||
IXE 80 mg Q2W±csDMARD | 103 | <0.001 | 62.1 | 46.6 | 34 | 0.08 | −0.5 | 76.9 | 38.6 | 79.7 | ||||
ADA 40 mg Q2W±csDMARD | 101 | <0.001 | 57.4 | 38.6 | 25.7 | 0.1 | −0.37 | 77.8 | 33.3 | 54.4 | ||||
Nash et al
(SPIRIT-P2)2 | TNFi-IR | Low | Placebo±csDMARD | 118 | ACR20 (week 24) | Ref | 19.5 | 5.1 | 0 | −0.2 | 8.5 | |||
IXE 80 mg Q4W±csDMARD | 122 | <0.001 | 53.3 | 35.2 | 22.1 | −0.6 | 31.1 | |||||||
IXE 80 mg Q2W±csDMARD | 123 | <0.001 | 48 | 33.3 | 12.2 | −0.4 | 33.3 | |||||||
Nash et al
(FUTURE-3)3 | Mixed csDMARD/bDMARD-IR | Low | Placebo±MTX | 137 | ACR20 (week 24) | Ref | 16.1 | 8.8 | −0.17 | 13.9 | 15.3 | 10.2 | ||
SEC 300 mg without LD±MTX | 139 | <0.001 | 48.2 | 34.5 | −0.38 | 47.8 | 39.8 | 46.8 | ||||||
SEC 150 mg without LD±MTX | 138 | <0.001 | 42 | 18.8 | −0.27 | 38.9 | 36.8 | 50 | ||||||
Kivitz et al
(FUTURE-4)4 | NSAID-IR | Abstract | Placebo±MTX | 114 | ACR20 (week 16) | Ref | 18.4 | 6.1 | 8.1 | 8.1 | ||||
SEC 150 mg with LD±MTX | 114 | <0.001 | 41.2 | 22.8 | 2.5 | 52.7 | ||||||||
SEC 150 mg without LD±MTX | 113 | <0.001 | 39.8 | 16.8 | 17.2 | 50 | ||||||||
Mease et al
(FUTURE-5)5 | Mixed | Low | Placebo±MTX | 332 | ACR20 (week 16) | Ref | 27.4 | 8.1 | 4.2 | 0.5* | −0.21 | 32.3 | 35.4 | 12.3 |
SEC 300 mg with LD±MTX | 222 | <0.001 | 62.6 | 39.6 | 20.3 | 0.08* | −0.55 | 65.9 | 55.7 | 70 | ||||
SEC 150 mg with LD±MTX | 220 | <0.001 | 55.5 | 35.9 | 18.2 | 0.17* | −0.44 | 57.5 | 54.6 | 60 | ||||
SEC 150 mg without LD±MTX | 222 | <0.001 | 59.5 | 32 | 14.9 | −0.09* | −0.45 | 56.3 | 41.9 | 58.1 | ||||
IL-23p19 inhibitors | ||||||||||||||
Deodhar et al 6 | Mixed csDMARD/TNFi-IR | Low | Placebo±MTX | 49 | ACR20 (week 24) | Ref | 18 | 10 | 2 | −0.06 | 17 | 29 | 13 | |
GKM 100 mg±MTX | 100 | <0.001 | 58 | 34 | 14 | −0.42 | 55 | 57 | 79 | |||||
Mease et al (ACR)7 | Mixed MTX/TNFi-IR | Abstract | Placebo±MTX | 42 | ACR20 (week 16) | Ref | 35.7 | 11.9 | 0 | 0.6* | −0.09 | 9.5 | ||
RKM 150 mg Q4W±MTX | 42 | <0.05 | 57.1 | 23.8 | 14.3 | −0.3* | −0.18 | 75.0 | ||||||
RKM 150 mg weeks 0, 4 and 16±MTX | 42 | <0.01 | 61.9 | 23.8 | 7.1 | 0.2* | −0.16 | 70.0 | ||||||
RKM 150 mg weeks 0 and 12±MTX | 39 | <0.05 | 59.0 | 38.5 | 25.6 | −0.5* | −0.25 | 73.9 | ||||||
RKM 75 mg week 0±MTX | 20 | <0.05 | 65.0 | 25.0 | 15.0 | −0.2* | −0.16 | 66.7 | ||||||
Other bDMARDs | ||||||||||||||
Mease et al 9 | NSAID/csDMARD-IR | Low | Placebo±MTX | 41 | 16 | Ref | 29.3 | 7.3 | 0.1 | −0.27 | 14.6 | |||
CKM 25 mg±MTX | 41 | 0.101 | 46.3 | 29.3 | 28.6 | −0.44 | 12.2 | |||||||
CKM 100 mg±MTX | 42 | 0.039 | 52.4 | 35.7 | 24.9 | −0.4 | 16.7 | |||||||
CKM 200 mg±MTX | 41 | 0.178 | 39 | 17.1 | 16.5 | −0.26 | 4.9 | |||||||
Mease et al
(ASTRAEA)8 | Mixed csDMARD/TNFi-IR | Low | Placebo±MTX | 211 | ACR20 (week 24) | Ref | 22.3 | 19.2 | 10.3 | 0.3 | −0.2 | 34 | 21.2 | 10.1 |
ABA±MTX | 213 | <0.001 | 39.4 | 12.3 | 6.6 | 0.35 | −0.33 | 44.3 | 32.9 | 16.4 | ||||
Mease et al 10 | MTX-IR | Low | Placebo+MTX | 24 | ACR20 (week 12) | Ref | 25 | 12.5 | 4.2 | −0.28 | 27 | |||
ADA 40 mg Q2W+MTX | 72 | NR | 68.1 | 37.5 | 15.3 | −0.58 | 57.6 | |||||||
ABT-122 120 mg Q2W | 71 | <0.001 | 64.8 | 36.6 | 22.5 | −0.55 | 74.4 | |||||||
ABT-122 240 mg Q2W | 73 | <0.001 | 75.3 | 53.4 | 31.5 | −0.56 | 77.6 |
*Week 24.
ABA, abatacept; ACR, American College of Rheumatology; ADA, adalimumab; bDMARD, biological disease-modifying antirheumatic drug; CKM, clazakizumab; csDMARD, conventional synthetic disease-modifying antirheumatic drug; GKM, guselkumab; HAQ-DI, Health Assessment Questionnaire Disability Index; IL, interleukin; IR, insufficient responders; IXE, ixekizumab; LD, loading dose; mTSS, PsA modified total Sharp score; MTX, methotrexate; NR, not reported; NSAID, non-steroidal anti-inflammatory drug; PASI, Psoriasis Area and Severity Index; PsA, psoriatic arthritis; Q2W, every 2 weeks; Q4W, every 4 weeks; Ref, reference arm; RKM, risankizumab; RoB, risk of bias; SEC, secukinumab; TNF, tumour necrosis factor; TNFi, TNF inhibitor.