Secukinumab versus guselkumab in the complete resolution of ustekinumab‐resistant psoriatic plaques: The ARROW study

Interleukin (IL)‐23–independent IL‐17A production has been suggested to be involved in persistent manifestations of psoriatic disease, including anti–IL‐12/23–refractory psoriatic plaques; this study aimed to test this hypothesis by investigating the clinical and molecular effects of direct IL‐17A (with secukinumab) versus selective IL‐23 inhibition (with guselkumab) in patients with anti–IL‐12/23 (ustekinumab)–refractory psoriatic plaques. A 16‐week, randomized, open‐label, parallel‐group, Phase IIa study (ARROW, NCT03553823) was conducted in patients with ≥1 active psoriatic plaque (total clinical score [TCS] ≥6) at screening despite treatment with ustekinumab, and a Psoriasis Area and Severity Index (PASI) score 1–10. Patients were randomized 1:1 to receive secukinumab 300 mg (n = 20) or guselkumab 100 mg (n = 20). Biopsies from one refractory (‘target plaque’) were obtained at baseline and Week 16. The primary endpoint was the proportion of patients whose ustekinumab‐refractory target plaque achieved clear/almost clear status (TCS 0–2) at Week 16. Transcriptomic and histological analyses were conducted on target plaques to determine the molecular effects of direct IL‐17A versus selective IL‐23 inhibition. At Week 16, target plaque clear/almost clear status was achieved in 60.0% of patients treated with secukinumab versus 40.0% of patients treated with guselkumab (p = 0.1715). Molecular analyses identified that secukinumab modulated a greater proportion of psoriasis disease transcriptome genes (72.1% vs. 48.0%) and resulted in more histological responders (72.2% vs. 53.3%) compared with guselkumab. Secukinumab demonstrated a greater clinical and molecular effect on ustekinumab‐refractory psoriatic plaques versus guselkumab. These results are consistent with the hypothesis that IL‐23–independent IL‐17 mechanisms may be relevant to the inflammation driving refractory manifestations of psoriasis.


| INTRODUC TI ON
2][3][4] The IL-17 family of cytokines consists of six members: IL-17 A-F.IL-17A is a homodimer and the prototypical member of the IL-17 family, and it is the well-established dominant effector cytokine of skin and joint inflammation in psoriasis.IL-17F (which can exist as a homodimer or as a heterodimer with IL-17A [i.e.IL-17A/F]) and IL-17C have, however, more recently been implicated in perpetuating inflammation in psoriasis. 1,5,6As such, psoriasis is typically treated with biologic compounds targeting either the IL-17 cytokine directly or targeting molecules upstream of the IL-17 pathway (e.g.IL-23 inhibitors, IL-12/IL-23 inhibitors and tumour necrosis factor α [TNFα] inhibitors).IL-17A is the signature cytokine of T helper (Th) 17 cells; however, several other cell types can also produce this cytokine, including adaptive immune cells (e.g.cytotoxic T [Tc]17 cells, [7][8][9] gamma-delta [γδ] T cells 10 ) and innate immune cells (e.g.mucosal-associated invariant T [MAIT] cells, 11 invariant natural killer T [iNKT] cells, 12 and innate lymphoid cells [ILCs] 13 ).The current pathogenic model of psoriasis depends on IL-23-dependent production of IL-17A and IL-17F.
Dendritic cell (DC) production of IL-23 induces Th17 polarization and IL-17A/IL-17F expression; IL-17A/IL-17F act on keratinocytes to induce skin inflammation and production of IL-17C and IL-36, which positively feedback on Th17 cells. 14,15-17A and IL-17F are produced primarily in an IL-23-dependent manner.16 However, there is evidence for IL-23-independent production of IL-17A via a subset of immune cells that possess the T cell receptor, such as Tc17, MAIT cells, iNKT cells, and ILCs.8,[11][12][13] IL-17F may also be produced independent of IL-23; however, these data are limited and further analyses are warranted to understand the role of non-Th17-derived IL-17F.[17][18][19] Of interest, Liu et al. recently identified two transcriptionally diverse Tc17 cell subsets in psoriatic lesions based on high expression of both IL-17A and IL-17F; these subsets also had cytotoxic potential and expressed Th1 and Th22 cytokines.20 Furthermore, although it has generally been accepted that IL-17A production occurs downstream of IL-23, a recent publication from Ehst et al. demonstrated that IL-23 production could also be induced by IL-17A, suggesting a bidirectional relationship between IL-17A and IL-23. 21Recent evidence suggests that IL-23-independent production of IL-17A through mechanisms such as those mentioned above may be responsible for persistent disease involvement in the skin and other hard-to-treat areas in patients with plaque psoriasis undergoing treatment with anti-IL-12/23 therapy.[22][23][24] This is supported by a lack of efficacy of ustekinumab and risankizumab in axial spondyloarthritis.25,26 Further, Jack et al. demonstrated that plaques which remain active in patients who otherwise respond to ustekinumab have a persistent expression of IL-17A and plaque infiltration of IL-17A + cluster of differentiation (CD) 3 + T cells at a level similar to untreated patients.27 The direct neutralization of IL-17A may allow inhibition of its biologic activity irrespective of its cellular source, overcoming the issue of IL-23-independent IL-17A release and inflammation.Therefore, we hypothesized that direct inhibition of the effector cytokine IL-17A through secukinumab treatment may be superior to selective IL-23 inhibition with guselkumab (through p19 subunit targeting) in controlling those clinical manifestations where IL-23-independent release of IL-17A may be the main driver of plaque psoriasis.
The ARROW study (NCT03553823) was a 16 • Ustekinumab was administered at a dose equal to or higher than that on the label for at least 24 weeks.The last administration must have been ≥12 weeks before randomization.
• Absolute Psoriasis Area and Severity Index (PASI) score of 1-10 at screening.
• Presence of at least one refractory skin plaque, defined by a total clinical score (TCS) of ≥6 and a severity score of at least 2 or 3 (moderate) for each individual item, with an area ≥ 10 cm 2 at screening and baseline.
For each included patient, one refractory plaque was identified as the study 'target plaque' to assess all outcomes of investigational treatment.TCS for the target plaque was calculated as the sum of erythema, scaling, and infiltration scores, rated according to severity (range of 0 [all signs absent] to 9 [all signs present]).

| Clinical study outcomes
The primary endpoint of this study was the proportion of patients whose ustekinumab treatment-refractory target plaque achieved a 'clear' or 'almost clear' status (TCS of 0-2) following 16 weeks of treatment with either secukinumab or guselkumab.The primary clinical endpoint was analysed at Week 16 given that the primary outcome measures for two of the guselkumab registrational trials were also taken at Week 16. 29,30 Additional exploratory clinical endpoints included the change from baseline to Week 16 in joint pain (score based on a visual analogue scale [VAS] 0-100), absolute PASI score, body surface area, Investigator's Global Assessment (IGA), Nail Psoriasis Severity Index (NAPSI), Psoriasis Scalp Severity Index (PSSI), and Palmoplantar Investigator's Global Assessment (ppIGA).Further information on exclusion criteria, prohibited treatments, sample collection, safety analyses, statistical analysis of clinical data, and ethical considerations are described in the Supplementary Methods.

| Analysis of the psoriasis disease transcriptome
Messenger ribonucleic acid (mRNA) sequencing (RNASeq), microarray analysis, and quantitative real-time polymerase chain reaction (qRT-PCR) were conducted to examine mRNA expression (see Supplementary Methods).The psoriasis disease transcriptome (PSTR) was determined using whole-genome profiling as previously described. 31,32Briefly, the PSTR was defined as the genes differentially expressed between baseline lesional (LS) and non-lesional (NL) skin with a fold change (FCH) absolute value ≥1.5 and a false discovery rate (FDR) ≤0.05.Furthermore, the effect of secukinumab and guselkumab treatment on previously published meta-transcriptomic datasets (including the meta-analysis-derived [MAD]-3 transcriptome) was examined.See Brodmerkel et al. for more information on psoriasis gene sets included in the analysis. 32

| Immunohistochemistry analysis
General histopathology of the skin was assessed using haematoxylin and eosin staining and epidermal proliferation and differentiation  The study was completed by 39 (97.5%) patients; only 1 patient in the guselkumab group discontinued (physician decision).Table 1 describes baseline patient demographics and disease characteristics.

| Study population
In the total population, the mean age and weight were 48.1 ± 13.60 years and 101.2 ± 24.85 kg, respectively.Overall, 72.5% of patients were male, and 92.5% were white.Baseline demographics were well-balanced between treatment arms with a mean disease duration of 22.5 ± 11.

| Clinical efficacy results
The primary endpoint of this study (i.e.superiority of secukinumab over guselkumab) was not met.However, the number and percentage of patients who responded to treatment, as assessed at Week 16 (patients achieving a clear/almost clear status [TCS of 0-2]), were numerically higher in the secukinumab arm (60.0%[95% confidence interval: 36.1-80.9])than in the guselkumab arm (40.0%[95% confidence interval: 19.1-63.9]).Nonetheless, no statistically significant difference (20.0%; p = 0.1715) was found between the arms (Figure 1A).Treatment with secukinumab resulted in a decrease in the mean joint pain score (VAS) at Week 16 (−22.3± 26.70) compared with baseline, whereas treatment with guselkumab caused a small increase in the mean score (7.8 ± 18.80; Figure 1B).Both secukinumab and guselkumab treatments resulted in a reduction of additional exploratory clinical endpoints (BSA, PASI, IGA, total NAPSI, finger NAPSI, PSSI, ppIGA) at Week 16; in all clinical endpoints except PSSI, the treatment effect was numerically higher with secukinumab versus guselkumab (Table S1).
Of interest, CIR in both secukinumab and guselkumab arms had a ).In terms of safety, the rates of adverse events were similar between treatment arms, and the rates of treatment-emergent serious adverse events were low (secukinumab, n = 2; guselkumab, n = 1).Clinical safety analyses are further detailed in the Supplementary Results and Table S3.

| Characterization of ustekinumab-resistant psoriatic lesions prior to treatment
The qRT-PCR analysis of gene expression in ustekinumab-resistant lesions showed >10-fold increased expression of IL17A, IL17F and IL17C mRNA in LS skin (p < 0.001 for all) versus NL skin at baseline (Figure 2).Baseline lesions also had elevated expression of IL23A and K16 mRNA, as expected in untreated psoriasis lesions.Histological examination of ustekinumab treatment-resistant psoriatic lesions at baseline showed typical features, including epidermal acanthosis, elongated rete ridges, increased presence of Ki67 + (proliferation marker) keratinocytes, K16 expression by suprabasal keratinocytes  a Of patients with PsA at screening, specific sites affected were captured for three patients, all in the guselkumab arm; of these patients, all three had distal inter-phalangeal joint arthritis and one of these patients also had both asymmetric peripheral arthritis and spondylitis.
b Only reported for those patients experiencing joint pain at baseline (n = 8 for both secukinumab and guselkumab arms).
TA B L E 1 Baseline demographics and disease characteristics.

| DISCUSS ION
The ARROW study was designed to assess whether direct inhibition       therapy also led to nearly complete resolution of clinical, histologic, and transcriptomic features of psoriasis. 31In that study, and similarly to the current study, the resolution of PSTR genes was markedly different between CR and CIR.

S U PP O RTI N G I N FO R M ATI O N
Additional supporting information can be found online in the Supporting Information section at the end of this article.

28 2 | ME THODS 2 . 1 |
-week, randomized, open-label, active-controlled, Phase IIa study developed to investigate the effects of direct IL-17A inhibition versus IL-23 inhibition in patients with an inadequate response to ustekinumab (i.e.patients who had a response to the IL-12/23p40 inhibitor ustekinumab that was incomplete, having refractory plaques that remained active despite treatment).Further, ARROW aimed to test the hypothesis that IL-23-independent IL-17 mechanisms are relevant to the inflammatory activity of refractory manifestations of psoriatic disease.Guselkumab was chosen as an active comparator (as a selective inhibitor of the p19 subunit of IL-23 without collateral disruption of the IL-12 signalling pathway) given its sole approval at the time of ARROW's design and initiation; the IL-12 signalling pathway has been previously suggested to have a protective role in the imiquimod-induced mouse psoriasis model.Study design and patients ARROW was a 16-week, randomized, open-label, parallel-group, active-control, Phase IIa, multicenter study conducted to assess the superiority of subcutaneous (s.c.) secukinumab 300 mg over s.c.guselkumab 100 mg in psoriatic plaques that were refractory to treatment with ustekinumab.Although this study had an open-label design, investigation of clinical and exploratory endpoints remained blinded.At baseline (Day 1, ≥12 weeks after the last administration of ustekinumab), 40 patients who had at least one active psoriatic plaque refractory to treatment with ustekinumab were randomly assigned (1:1) via the Novartis Interactive Response Technology to receive secukinumab or guselkumab.Secukinumab was selfadministered as two 150 mg s.c.injections at baseline and Weeks 1, 2, 3, 4, 8 and 12. Guselkumab was self-administered as a 100 mg s.c.injection at baseline, Week 4 and Week 12 (Figure S1).Patients aged ≥18 years with inadequately controlled chronic plaque-type psoriasis (inadequate responders [IR]) after treatment with ustekinumab were included according to the following criteria: were determined using immunohistochemistry (IHC) staining of Ki-67-and keratin 16 (K16)-positive nuclei, respectively.Positive cells were quantified at 200× magnification and calculated per millimetre of skin length.Furthermore, the number of infiltrating cells expressing IL-17A and IL-23R was assessed by single-staining immunofluorescence (IF) using IHC.Single and double staining (IHC/IF) were used to identify different cell types in the immune infiltrate according to the following markers: T cells (CD3, CD4, CD8), neutrophils (elastase), mast cells (tryptase), dendritic cells (CD11c), macrophages (CD163), natural killer T (NKT) cells (CD3, CD56), and resident memory T cells (CD49, CD103).The number of cells per cell type was counted per millimetre of skin length.Overall, 31/40 (77.5%) patients completed the biopsy series and were fully evaluable (17/20 [85.0%] in the secukinumab arm; 14/20 [70.0%] in the guselkumab arm).In both the secukinumab and guselkumab arms, one patient missed the pre-treatment NL biopsy; analysis of the treatment response was still carried out in this patient (i.e.LS and Week 16 biopsies).For statistical analysis of mechanistic data, please refer to the Supplementary Materials.
3 years in the secukinumab arm and 19.1 ± 12.5 years in the guselkumab arm.Overall, 11 patients (27.5%) had a diagnosis of psoriatic arthritis (PsA) at screening (3 [15.0%] in the secukinumab arm and 8 [40.0%] in the guselkumab arm).Eight patients (40%) in each arm reported the presence of joint pain (VAS) at baseline; in the secukinumab arm, 5/8 patients reporting joint pain at baseline had no PsA and in the GUS arm 2/8 patients reporting joint pain at baseline had no PsA.Nine patients (45.0%) from the secukinumab arm and 10 patients (50.0%) from the guselkumab arm reported prior biologic therapy other than ustekinumab.Baseline PASI and TCS were balanced between treatment arms at baseline.

F I G U R E 1 3 |
Week 16 clinical efficacy results.(A) Bar graph demonstrating the proportion of patients achieving a clear/almost clear (TCS 0-2) clinical response of target plaque at Week 16 following secukinumab 300 mg or guselkumab 100 mg treatment.(B) Line graph showing effect of secukinumab 300 mg or guselkumab 100 mg treatment on joint pain (VAS) at Week 16 in those patients reporting pain at baseline (n = 8 in each group).TCS, total clinical score; VAS, visual analogue scale.Effect of secukinumab and guselkumab on molecular profiles of inflammation qRT-PCR analysis demonstrated reductions in the expression of key IL-17/IL-23 pathway genes in response to both secukinumab and guselkumab treatment at Week 16 (Figure S6).Overall, secukinumab and guselkumab resulted in similar reductions in the expression of IL-17/IL-23 genes between baseline LS and Week 16 LS skin expression (Figure S6A).Analysis of the IL-17/IL-23 pathway genes in CR and CIR is shown in Figure S6B,C, respectively.In both CR and CIR, secukinumab and guselkumab significantly reduced expression of IL17A, IL17F and IL17C mRNA (FigureS6Bi-iii,Ci-iii).In CR, secukinumab and guselkumab resulted in a similar reduction of IL23A expression (FigureS6iv).However, in the guselkumab CIR group, BL LS expression of IL23A was not significantly upregulated and was unchanged at Week 16 whereas the heightened BL LS expression of IL23A in the secukinumab CIR group was downregulated at Week 16 (FigureS6Civ).

3. 3 . 4 |
Histology analysisOverall, 72.2%(13/18) of patients in the secukinumab and 53.3% (8/15) of patients in the guselkumab arms achieved a histological response at Week 16 (mirroring the clinical response), defined as clearing or elimination of psoriasis-like tissue patterning, thinning of the epidermis, reduced cell proliferation, and the absence of Krt16 staining.Both secukinumab and guselkumab treatment resulted in decreased expression of inflammatory cells (including CD8 + T cells, CD3 + T cells, CD103 + T resident memory cells, and CD11c DCs)F I G U R E 2 Characterization of baseline lesions in ustekinumab-resistant psoriatic plaques.Bar graphs demonstrating (A) RNA expression of the IL-17/IL-23 pathway genes in BL NL and BL LS skin using qRT-PCR and (B) protein expression of key markers in BL NL and BL LS skin in all patients.Data are represented as LSM ± SE for qRT-PCR and IHC data.Positive cells were quantified at 200× magnification.BL, baseline; CD, cluster of differentiation; hARP, human acidic ribosomal protein; IHC, immunohistochemistry; IL, interleukin; LS, lesional; LSM, least squares mean; mm, millimetre; RNA, ribonucleic acid; NL, non-lesional; qRT-PCR, quantitative real-time polymerase chain reaction; RNASeq, ribonucleic acid sequencing; SE, standard error; W, week.***p < 0.001, **p < 0.01, *p < 0.05.
and markers associated with psoriasis pathology (including elastase [neutrophils], tryptase [mast cells], and Ki67; FigureS7).Reductions of inflammatory cells and markers associated with psoriasis pathology were greater in CR (Figure6; FigureS8), with little improvements observed in CIR (FiguresS9 and S10).Furthermore, in line with transcriptional analyses, significant reductions from baseline in the number of infiltrating immune cells expressing IL-17A and IL-23R in LS skin from the combined CR/CIR group were observed in both treatment arms at Week 16; changes in IL-17A expression were more pronounced in LS skin from secukinumab-treated patients compared with guselkumab-treated patients, whereas changes in IL-23R expression were more pronounced following guselkumab treatment (FigureS11).

34 F I G U R E 5
of IL-17A through secukinumab treatment is superior to selective IL-23p19 inhibition through guselkumab treatment in clearing psoriatic plaques which remained active in patients who had partially responded to the IL-12/23p40 inhibitor ustekinumab.The design of the proof-of-concept, Phase IIa ARROW study, which recruited a highly specific patient population, provided an opportunity to explore IL-23-independent immune mechanisms in plaque psoriasis.Expression of IL-17A by innate inflammatory cells independently of IL-23 control is one of the pathophysiological mechanisms hypothesized to drive the continued inflammatory activity of ustekinumabrefractory psoriatic plaques.While IL-17A and IL-17F expression are markedly reduced in psoriatic lesions following successful treatment with ustekinumab, 32 the current study demonstrates that ustekinumab-refractory psoriatic lesions express high levels of IL17A, IL17F, and IL17C mRNA, indicative of a potential IL-17-driven escape mechanism.Furthermore, despite overexpression of IL23 mRNA, psoriatic plaques that are refractory to IL-12/23-targeted treatment seem to benefit more from IL-17A inhibition, rather than specific treatment through IL-23 inhibition; this is consistent with the hypothesis that IL-17-mediated immune mechanisms escaping IL-23 control are relevant in hard-to-treat/refractory manifestations of psoriatic disease.Secukinumab is efficacious in the treatment of ankylosing spondylitis (AS); this suggests a role for IL-17 in AS pathophysiology.Mauro et al. proposed that AS pathophysiology is perpetuated by the production of IL-17A by ILCs, thus providing further a potential rationale for the superior efficacy of direct IL-17A inhibition in AS.Improvement in psoriasis gene sets following 16 weeks of secukinumab or guselkumab treatment by clinical response.Bar graphs demonstrating mean percentage improvement at Week 16 from BL of PSTR genes by previously published gene sets related to psoriasis pathology following secukinumab 300 mg or guselkumab 100 mg treatment in (A) CR patients and (B) CIR patients based on RNASeq data.BL, baseline; CIR, clinical inadequate responder; CR, clinical responder; KC, keratinocyte; iDC, immature dendritic cells; IL, interleukin; LS, lesional; MAD, meta-analysis derived; mDC, monocyte-derived dendritic cell; mg, milligram; PSTR, psoriasis disease transcriptome; RHE, reconstructed human epidermis; RNASeq, ribonucleic acid sequencing; Th, T helper; W, week.***p < 0.001, **p < 0.01, *p < 0.05.

F I G U R E 6
Expression of cell surface markers following 16 weeks of secukinumab or guselkumab in clinical responder patients.Representative photomicrographs of BL NL, BL LS and Week 16 LS skin of CR patients following 16 weeks of treatment with either (A) secukinumab 300 mg or (B) guselkumab 100 mg.Images are shown in 10× magnification.BL, baseline; CD, cluster of differentiation; CR, clinical responder; H&E, haematoxylin and eosin; K16, keratin 16; LS, lesional; NL, non-lesional.Krueger et al. previously demonstrated the molecular effects of 12 weeks of secukinumab treatment in patients with moderate to severe psoriasis. 36By 12 weeks, secukinumab reversed plaque histopathology and modulated thousands of transcripts, suggesting early and substantial downregulation of feed-forward genes and indicating disruption of IL-17A-dependent feedback mechanisms following IL-17A neutralization with secukinumab. 36Similarly, brodalumab (IL-17 receptor A subunit antagonist that inhibits IL-17A, C, E and F) An additional limitation of the clinical aspect of this Phase IIa proof-of-concept study was the small sample size included in each treatment group which may have contributed to the primary endpoint being missed.This small sample size may have also provided for the small imbalance in PsA patients between the secukinumab and guselkumab arms; less patients in the secukinumab arm had PsA at screening, however, a greater number had joint pain at baseline, possibly indicating pre-clinical PsA.Further, this study only assessed the short-term (16 weeks) effects of secukinumab and guselkumab on clinical and molecular outcomes; longer-term conclusions cannot be extrapolated from this data.The key strength of the ARROW study was the inclusion of a highly specific patient population which provided an opportunity to monitor the macroscopic, microscopic, and molecular response to treatment of a single ustekinumab-refractory target plaque over time; this allowed for further investigation of the role of IL-23-independent immune mechanisms in psoriatic disease.In the ARROW study, secukinumab demonstrated a numerically higher clinical treatment effect, a significantly greater molecular effect in terms of impact on the PSTR, and a greater number of patients achieving a histological response versus guselkumab in treating ustekinumab-refractory psoriatic plaques.In conclusion, although the ARROW study does not prove that IL-23-independent IL-17mediated immune mechanisms are relevant in hard-to-treat/refractory manifestations of psoriatic disease, the results are consistent with this hypothesis.AUTH O R CO NTR I B UTI O N S Conceptualization: James Krueger, Kristian Reich, Gabriele Di Comite, Frank Kolbinger.Formal analysis: Christine-Elke Ortmann, Sandra Garcet.Investigation: James Krueger, Kristian Reich, Richard G. Langley, Simon Nigen, Sandra Garcet.Writing-Review and Editing: James Krueger, Richard G. Langley, Simon Nigen, Torben Kasparek, Gabriele Di Comite, Christine-Elke Ortmann, Sandra Garcet, Frank Kolbinger, Kristian Reich.

Figure S3 .
Figure S3.Modulation of the psoriasis transcriptome following 16 weeks of secukinumab or guselkumab treatment by clinical response.

Figure S4 .
Figure S4.Microarray analysis of modulation of the psoriasis transcriptome overall, and in clinical responders versus inadequate responders to secukinumab or guselkumab treatment.

Figure S5 .
Figure S5.Improvement in psoriasis gene sets following 16 weeks of secukinumab or guselkumab treatment by clinical response based on microarray analysis.

Figure S7 .
Figure S7.Expression of cell surface markers and markers associated with psoriasis pathology following 16 weeks of secukinumab or guselkumab treatment.

Figure S8 .
Figure S8.Expression of cell surface markers and markers associated with psoriasis pathology following 16 weeks of secukinumab or guselkumab treatment in clinical responder patients.

Figure S9 .
Figure S9.Expression of cell surface markers and markers associated with psoriasis pathology following 16 weeks of secukinumab or guselkumab treatment in clinical inadequate responder patients.

Figure S10 .
Figure S10.Histological expression of cell surface markers following 16 weeks of secukinumab or guselkumab in clinical inadequate responder patients.

Figure S12 .
Figure S12.Biomarker expression in tape strip and serum samples following 16 weeks of secukinumab or guselkumab treatment.Data S1.Supplementary methods and results.

Table S1 .
Mean change from Baseline to Week 16 in exploratory clinical endpoints.