Comparative Efficacy and Relative Ranking of Biologics and Oral Therapies for Moderate-to-Severe Plaque Psoriasis: A Network Meta-analysis

Abstract

Introduction: The clinical benefits of biologic and oral treatments for moderate-to-severe plaque psoriasis are well-established, but efficacy outcomes can vary across therapies. Comparative efficacy analysis can be highly informative in clinical settings with multiple therapeutic options. This study assessed the short-term and long-term comparative efficacy of biologic and oral treatments for moderate-to-severe psoriasis.

Methods: A systematic literature review identified phase 2/3/4 randomized controlled trials (RCTs) through to 1 July 2020 for Food and Drug Administration- or European Medicines Agency-licensed treatments for moderate-to-severe psoriasis. Psoriasis Area and Severity Index (PASI) 75/90/100 response rates at the end of the primary response (short-term: 10-16 weeks from baseline) and maintenance periods (long-term: 48-52 weeks from baseline) were estimated using Bayesian network meta-analysis. Surfaces under the cumulative ranking curves (SUCRA) were estimated to present the relative ranking of treatments.

Results: In the short term (N = 71 RCTs), the PASI 90 response rates were highest for ixekizumab (72.9%, SUCRA 0.951), risankizumab (72.5%, 0.940), and brodalumab (72.0%, 0.930), which were significantly higher than those for guselkumab (65.0%, 0.795), secukinumab (65.0%, 0.794), infliximab (56.8%, 0.702), certolizumab (400 mg: 49.6%, 0.607; 200 mg: 42.2%, 0.389), ustekinumab (90 mg: 47.9%, 0.568; weight-based: 45.7%, 0.505; 45 mg: 44.6%, 0.460), adalimumab (43.0%, 0.410), tildrakizumab (200 mg: 39.7%, 0.327; 100 mg: 37.2%, 0.268), etanercept (18.0%, 0.171), apremilast (12.4%, 0.090), and dimethyl fumarate (12.2%, 0.092). The PASI 100 response rates were highest for ixekizumab (41.4%), risankizumab (40.8%), and brodalumab (40.3%). In the long term (N = 11 RCTs), the PASI 90 rate was highest for risankizumab (85.3%, SUCRA: 0.998), which were significantly higher than those for brodalumab (78.8%, 0.786), guselkumab (78.1%, 0.760), ixekizumab (72.1%, 0.577), secukinumab (67.0%, 0.450), ustekinumab (weight-based: 55.0%, 0.252), adalimumab (51.6%, 0.176), and etanercept (37.9%, 0.001). Risankizumab had the highest PASI 100 response rate (65.4%), followed by brodalumab (55.7%) and guselkumab (54.8%).

Conclusions: Ixekizumab, risankizumab, and brodalumab had the highest short-term efficacy, and risankizumab had the highest long-term efficacy.

Keywords: Biologic therapies; Network meta-analysis; Plaque psoriasis.

Fig. 1

Study screening and selection flow. e1 exclusion 1, e2 exclusion 2, i1 inclusion 1, i2 inclusion 2, i3 inclusion 3, NMA network meta-analysis

Fig. 2

Evidence network for the network meta-analysis (NMA) of the Psoriasis Area and Severity Index (PASI) response by the end of the primary response period (short-term; 10–16 weeks after baseline). The included trials were: Asahina et al. [27], Bissonnette et al. [28], REVEAL [29], CHAMPION [30], Gordon et al. [31], Cai et al. [32], VIP [33], Leonardi et al. [34], Papp et al. [35], van de Kerkhof et al. [36], Gottlieb et al. [37], EXPRESS [38], EXPRESS II [39], SPIRIT [40], Chaudhari et al. [41], Torii et al. [42], Yang et al. [43], UNCOVER 1 [44], UNCOVER 2 [45], UNCOVER 3 [45], IXORA-S [10], IXORA-R [8], ERASURE [46], FEATURE [47], FIXTURE [46], JUNCTURE [48], CLEAR [49], CLARITY [11], VIP-S [50], ALLURE [51], ObePso-S [52], NCT03066609 [53], ACCEPT [54], LOTUS [55], PEARL [56], PHOENIX 1 [57], PHOENIX 2 [58], Igarashi et al. [59], VIP-U [60], Zhou et al. [61], X-PLORE [62], VOYAGE-1 [63], VOYAGE-2 [64], ORION [65], Ohtsuki et al. [66], ECLIPSE [21], Nakagawa et al. [67], Papp et al. [68], AMAGINE-1 [69], AMAGINE-2 [70], AMAGINE-3 [70], CIMPASI-1 [71], CIMPASI-2 [71], CIMPACT [72], NCT00245765 [73], NCT03051217 [74], reSURFACE-1 [75], Papp et al. [76], reSURFACE-2 [75], UltIMMa1 [77], IMMvent [78], IMMhance [79], SustalMM [80], IMMerge [9], BRIDGE [81], PSOR-008/ESTEEM-1 [82], PSOR-009/ESTEEM-2 [83], PSOR-010/LIBERATE [84], PSOR-005 [85], and Ohtsuki et al. [86]. BIW Twice weekly, QW once weekly

Fig. 3

Estimated numbers needed to treat (NNTs) relative to placebo for short-term PASI response. Values are presented with the 95% credible interval (Crl) in parenthesis. BIW Twice weekly, PASI 75, 90, 100 75, 90, or 100% decrease from baseline PASI, respectively, QW once weekly

Fig. 4

Evidence network for the NMA of PASI response by the end of the maintenance period (long-term; 48–52 weeks after baseline). The included trials were: AMAGINE-2 [70], ECLIPSE [21], VOYAGE-1 [63], CLEAR [87], FIXTURE [46], CLARITY [22], IXORA-S [88], UltIMMa1 [77], and IMMerge [9]