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Background: Psoriasis is a chronic inflammatory skin condition that impacts quality of life and requires long-term treatment and effective symptom management. Interleukin-23 (IL-23) has emerged as a key player in the pathogenesis of psoriasis and tildrakizumab and guselkumab are both immunomodulatory agents that inhibit the p19 subunit of IL-23. In its pivotal Phase III trial, tildrakizumab demonstrated greater efficacy than etanercept in moderate-to-severe psoriasis. However, there are no head-to-head trials comparing tildrakizumab with guselkumab. Methods: We conducted a systematic literature review and Bucher indirect comparison of tildrakizumab and guselkumab, using placebo as a common comparator. We searched MEDLINE, MEDLINE In-Process, MEDLINE(R) Daily Epub Ahead of Print, and Cochrane Central Register of Controlled Trials for Phase III randomized controlled trials between 1946 and November 2018. Inclusion criteria were adult patients ≥18 years with moderate-to-severe chronic plaque psoriasis, and intervention with tildrakizumab or guselkumab compared to placebo or best supportive care. Outcomes included were severity of psoriasis as defined by the Psoriasis Area and Severity Index (PASI) 75 and PASI 90, frequency of serious adverse events (SAEs), and treatment discontinuations. Outcomes were evaluated at Weeks 12 to 16 and 24 to 28. Analysis was based on the intent-to-treat population and, for all outcomes, the number of events reported were analyzed as a proportion of the number of patients randomized to ensure consistency across trials. Results: Overall, 154 unique records were identified. Five studies met the eligibility criteria and were included in the analysis; two tildrakizumab trials (reSURFACE 1 and reSURFACE 2) and three guselkumab trials (VOYAGE 1, VOYAGE 2, and a Japanese study). There was no statistically significant difference between guselkumab and tildrakizumab for PASI 75, PASI 90, SAEs, and rate of discontinuations at either timepoint. Conclusion: This study assessed the comparative efficacy of tildrakizumab and guselkumab for the treatment of moderate-to-severe psoriasis. Limitations included the limited number of publications, imputation of placebo arm values for Weeks 24 to 28, and limited relevance of the Japanese study. This indirect comparison does not provide evidence that one treatment is superior to the other.

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Abstract.We show the consistency of CH and the statement "no ccc forcing has the Sacks property" and derive some consequences for ccc ω ω -bounding forcing notions.In the last few years much progress has been made in studying properties of ccc posets in connection with partition properties. Many of these results deal with the Sacks property: recall that a poset P has the Sacks property if for any real r in the generic extension there is a sequence of finite subsets of ω, {I n } n ∈ V , such that r ∈ n<ω I n and |I n | ≤ 2 n for any n. Notice that when replacing the function f (n) = 2 n by an arbitrary increasing function we get an equivalent formulation. Jensen deduced in [3] the existence of ccc posets with the Sacks property from 3. Extracting a more general statement about ccc forcings, Veličković showed in [10] that it is possible to have a large continuum and the existence of ccc posets with the Sacks property. On the other hand, Shelah and Veličković showed independently that it is consistent that no ccc forcing has the Sacks property; see [6] and [11]. However, in the models they built the continuum is equal to ℵ 2 , so the question arises whether it is consistent with CH that no ccc forcing has the Sacks property. It turns out that the answer is yes. In this paper we derive this statement and some consequences for ccc ω ω -bounding forcing notions from a combinatorial Ramsey-type principle. This principle is known to be consistent with CH, as was proved by Abraham and Todorčević in [1].The notation we use is standard and might be found in [4] or [2]. If T is a tree in 2 <ω and s ∈ T , then we denote by T [s] the subtree of T with stem s, i.e. T [s] = {t ∈ T | t s ∨ s t}.

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