# Patient Profiles in Randomized Controlled Trials Versus a Real-World Study in Psoriatic Arthritis: Scoping Review and Metaanalysis

Gelsomina Alle, Clementina Lopez-Medina, Stefan Siebert, Frédéric Lavie, Wim Noel, Josef Smolen, Laure Gossec

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## To cite this version:

Gelsomina Alle, Clementina Lopez-Medina, Stefan Siebert, Frédéric Lavie, Wim Noel, et al. Patient Profiles in Randomized Controlled Trials Versus a Real-World Study in Psoriatic Arthritis: Scoping Review and Metaanalysis. Journal of Rheumatology, 2025, 52 (2), pp.jrheum.2024-0653. 10.3899/jrheum.2024-0653. hal-05503455

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Submitted on 10 Feb 2026

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**Short running head:** RCTs vs real-world PsA

**Full title of manuscript:** Patient profiles in randomised controlled trials versus a real-world study, in psoriatic arthritis: scoping review and meta-analysis.

**Complete given names and surnames of all authors with ORCID IDs:**

Gelsomina Alle<fnref n="1" />: 0000-0001-8091-2867

Clementina Lopez-Medina<fnref n="2" />: 0000-0002-2309-5837

Stefan Siebert<fnref n="3" />: 0000-0002-1802-7311

Frédéric Lavie<fnref n="4" />: 0000-0002-5213-257X

Wim Noel<fnref n="5" />: 0000-0002-5988-4627

Josef S. Smolen<fnref n="6" />: 0000-0002-4302-8877

Laure Gossec⁷: 0000-0002-4528-310X

**Key Indexing Terms:** psoriatic arthritis, registries, biological therapy, randomised controlled trial, meta-analysis

**Source(s) of support in the form of grants or industrial support:** The meta-analysis was supported by Assistance Publique - Hôpitaux de Paris (AP-HP). The PsABio study was sponsored by Janssen.

**Initials, surnames, appointments, and highest academic degrees of all authors (e.g., MD, PhD), and affiliated department(s) and institution(s):**

<footnote n="1">¹ G. Alle, MD, Rheumatology Unit, Pitié-Salpêtrière University Hospital, AP-HP, Paris, France and Rheumatology Section, Internal Medicine Service, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.</footnote>

<footnote n="2">² C. Lopez-Medina, PhD, Rheumatology Department, Reina Sofía University Hospital, IMIBIC, University of Cordoba, Cordoba, Spain and Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Université, INSERM, Paris, France.</footnote>

<footnote n="3">³ S. Siebert, PhD, School of Infection and Immunity, University of Glasgow, Glasgow, United Kingdom.</footnote>

<footnote n="4">⁴ F. Lavie, PhD, Johnson & Johnson Innovative Medicine, Paris, France.</footnote>

<footnote n="5">⁵ W. Noel, PhD, Johnson & Johnson Innovative Medicine, Beerse, Belgium.</footnote>

<footnote n="6">⁶ J.S. Smolen, PhD, Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria.</footnote>
⁷ L. Gossec, PhD, Rheumatology Unit, Pitié-Salpêtrière University Hospital, AP-HP and Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Université, INSERM, Paris, France.

**Conflicts of interest:** Gelsomina Alle has no conflicts of interest to declare. Clementina Lopez-Medina has received grant/research support from UCB, Novartis, Janssen, Abbvie and Lilly; and consulting fees from AbbVie, Eli Lilly, Novartis, UCB. Stefan Siebert has received grant/research support from Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, and UCB; and honoraria/speaker fees from AbbVie, Amgen, AstraZeneca, Eli Lilly, GlaxoSmithKline, Janssen, Teijin Pharma and UCB. Frédéric Lavie is an employee of J&J. Wim Noel is an employee of J&J and hold shares in the company. Josef S. Smolen has received grant/research support from AbbVie, AstraZeneca, Janssen, Novartis, Pfizer Inc, Roche; and consulting fees from AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Lilly, MSD, Novartis-Sandoz, Pfizer Inc, Roche, Samsung, Sanofi, UCB. Laure Gossec has received grant/research support from AbbVie, Biogen, Lilly, Novartis, UCB; and consulting fees from AbbVie, Amgen, BMS, Celltrion, Janssen, Lilly, MSD, Novartis, Pfizer, Stada and UCB.

**Corresponding author's name, address, and email:** Professor Laure Gossec.

Postal address: Hôpital Pitié-Salpêtrière, Service de Rhumatologie, 47-83 Boulevard de l'Hôpital, 75013 Paris, France. Email address: [laure.gossec@aphp.fr](mailto:laure.gossec@aphp.fr)

**Statement of ethics and consent:** The PsABio study was conducted according to Good Clinical Practice guidelines, complies with the Declaration of Helsinki, and was approved by the appropriate local ethical committees. Written informed consent was obtained from all participants.
## Abstract

**Objectives:** Patients with psoriatic arthritis (PsA) in randomised controlled trials (RCTs) may not reflect patients in clinical practice. The objective was to perform a meta-analysis of PsA patients' characteristics in RCTs of biologic disease-modifying antirheumatic drugs (bDMARDs), and to compare them to patient profiles in a real-world study.

**Methods:** Data sources: (a) Scoping literature review of phase III RCTs of bDMARDs in PsA published 2015-2020; (b) International observational study of PsA patients starting a bDMARD enrolled in 2015-2018 (PsABio: NCT02627768). Data collected at baseline included swollen and tender joint counts (SJC/TJC), enthesitis, skin involvement (body surface area -BSA-), C-reactive protein (CRP), physician global assessment (PhGA) and patient-reported outcomes (HAQ, pain). Univariate random-effects meta-analysis was conducted to calculate pooled means and proportions.

**Results:** Overall, 5654 patients from 10 RCTs were compared to 930 PsABio patients. Demographic data were similar. SJC/TJC were higher in RCTs than in PsABio (pooled means, 11.8/21.5 vs 5.7/11.9 respectively); enthesitis was more frequent in RCTs (64.7% vs 48.2%); as were patients with a BSA≥3% (62.2% vs 54.0%). PhGA was higher in RCTs (59.7mm vs 54.1mm). In contrast, patient-reported outcomes were similar, while CRP was significantly higher in PsABio (1.1 vs 1.4mg/dl).

**Conclusion:** PsA patients starting a bDMARD in RCTs had highly active disease and a high patient-reported disease burden. In contrast, PsABio real-world patients starting a bDMARD had lower joint counts, skin disease and PhGA, but presented with similar patient-reported disease burden. The extrapolation of RCT data in clinical practice should take these elements into account.

## Introduction

Psoriatic arthritis (PsA) is a highly heterogeneous inflammatory musculoskeletal disease. Treatment decisions are traditionally based on evidence from randomised controlled trials (RCTs) (1,2). However, RCTs of biologic disease-modifying anti-rheumatic drugs (bDMARDs) in PsA have historically used strict inclusion/exclusion criteria, which may lead to trial populations not completely representative of patients in routine clinical practice (3,4). Comparisons between patients studied in RCTs and patients receiving a bDMARD outside the setting of a controlled trial are needed to assess the generalisability of RCTs results for clinical practice. This would help to understand the limitations of trial results and the applicability of available data on patients and patient profiles, frequently seen in practice (5). Indeed, we did not identify studies comparing patients in usual care in need of a bDMARD therapy with those included in RCTs of bDMARDs.

The PsABio study was a multinational observational study of patients with PsA who started a bDMARD between 2015 and 2018, in routine care (6). This large-scale study offered an opportunity to compare these patients to patients included in RCTs over the same period of time.
The objective of the present study was to compare PsA patients'
characteristics included in RCTs of bDMARDs, to patient profiles in a real-world
study (PsABio) over a similar timeframe, using a meta-analysis of RCTs.

Methods

We obtained an overview of patient characteristics in trials through a scoping
literature review and meta-analysis of RCTs in PsA, then compared the findings to
patient characteristics from the real-world observational study, PsABio.

**Data sources and eligibility criteria**

a) **Published RCTs:**

A literature search was performed with reference to the PRISMA scoping
review guidelines (7), to identify primary publications of phase III RCTs of bDMARD
treatments in patients with PsA. A scoping review was chosen to provide an overview
of patient characteristics, without assessing treatment efficacy, as this method is
appropriate for broad exploratory questions and mapping available evidence (8). The
literature review could not be registered in PROSPERO, due to its nature (scoping
review) (9). To cover the same time-frame as our observational study PsABio, we
selected papers published 2015-2020. The literature search was conducted in
PubMed database in September 2023, with keywords related to PsA, phase III, RCT.
The papers underwent title/abstract then full-text reviews, and after applying the
selection criteria (primary publication of a bDMARD trial in PsA patients, placebo-
controlled), 10 RCTs were selected for analysis (10–19). Only baseline data were
analysed.

b) **Real-world data:**

The PsABio study (ClinicalTrials.gov: NCT02627768) was a multinational, prospective, observational study of PsA patients enrolled 2015-2018, at 92 study sites in eight European countries (6). Eligible participants were adults with PsA (according to the rheumatologist's diagnosis and fulfilment of CASPAR criteria). Start of a bDMARD (either a tumour necrosis factor inhibitor -TNFi- or ustekinumab), as first-, second- or third-line therapy for PsA, at the discretion of the treating rheumatologist was the only inclusion criterion, not a particular disease activity level. Here, only baseline data were analysed. This study complied with all ethics requirements and patients gave their consent, as previously reported (6).

Data collection

**_General data._** Demographic data and clinical characteristics were collected at baseline, including disease duration, previous bDMARDs usage, and other concomitant PsA medication (methotrexate and corticoids).

**_Disease activity assessments._** The following baseline PsA disease features were assessed: Swollen Joint Count (SJC) and Tender Joint Count (TJC), presence of enthesitis (yes/no and Leeds Enthesitis Index [LEI]), presence of dactylitis (yes/no and dactylitis count), psoriasis body surface area (BSA), presence of nail disease (yes/no), physician global assessment (PhGA - assessed on a Visual Analogue Scale [VAS] 0-100 mm), and C-reactive protein (mg/dL).

**_Patient-reported outcomes._** Health Assessment Questionnaire – Disability Index (HAQ-DI), patient global assessment (PGA) for disease activity, and pain (VAS 0-100 mm) were collected.
**Fulfilment of the criteria for RCTs.** The inclusion/exclusion criteria of the selected RCTs were collected and the PsABio population was compared to these criteria.

## Statistics

All patients from RCTs (whatever the treatment arm) were analysed together. When the data were presented only by treatment arm, weighted means and standard deviations (SD) were calculated for continuous variables, and percentages were recalculated for discrete data. The baseline characteristics of patients in the RCTs were pooled using univariate random effects meta-analysis. Pooled means and pooled proportions and their 95% confidence intervals (CI) were calculated for continuous and binary variables, respectively. On PsABio, descriptive statistics were performed. Finally, comparisons between the metanalysed pooled data and the observational study PsABio were performed by non-parametric tests, Wilcoxon test and z-test statistics, for indicative purposes. R Studio version 1.4.1106 and the "metafor" package were used for these analyses.

## Results

### Metanalysis of RCTs - Literature search

After screening 97 publications from the 2015-2020 period (Supplementary Figure S1), 10 primary publications of phase III RCTs of bDMARD treatments in patients PsA were analysed, corresponding to 5654 patients in total (10–19). The recruitment dates in the trials ranged 2011-2018. Study characteristics are shown in Supplementary Table S2.

### Demographic characteristics

**Patient characteristics in RCTs.** Of the 5654 patients, 50.7% were female, with a disease duration around 6 years (Table 1). Across the trials, 72.0% of patients were biologic-naïve, and 49.6% (range of means 41.0-70.0%) of patients received methotrexate at baseline.

**Patient characteristics in PsABio.** Of 930 participants in PsABio who began treatment, 49.2% started ustekinumab and 50.7% a TNFi. While overall, demographic data were very similar across the data sources (Table 2), PsABio patients were much less frequently bDMARD-naïve (50.4%) than the RCTs participants.

### Baseline disease activity

**Disease activity in RCTs (Table 1, Figure 1 and Supplementary Figure S3).** The pooled mean SJC and TJC were 11.8 (95% CI 6.5-17.1) and 21.5 (95% CI 12.5-30.6), respectively. Enthesitis was observed in 64.7% of patients (range 58.0-76.3%), and dactylitis in 37.7% (range 17.1-53.8%). As regards skin involvement, 62.2% (range 48.4-82.1%) of patients had a BSA≥3%.

**Disease activity in PsABio.** Disease activity by physical examination was lower than in the RCTs: SJC and TJC were 5.7 (SD 7.6) and 11.9 (SD 11.6) (p<0.001), respectively (Table 2); enthesitis and dactylitis were less frequent (48.2%, p<0.001; and 19.8%, p<0.001; respectively) and skin involvement with a BSA≥3% concerned less patients (54.0%, p<0.001) (Table 2).

### Patient-reported impact of disease
In both data sources, there was a high and comparable patient-reported burden of disease, with mean pain levels and PGA both close to 60mm and HAQ-DI around 1.2 (Table 2).

### Global markers of disease activity

PhGA was statistically significantly higher in RCTs (59.7mm) than in PsABio (54.1mm), though the magnitude of difference was not high. Mean CRP was statistically significantly higher in PsABio (1.1 vs 1.4 mg/dl, p=0.002) (Table 2).

**Fulfilment of inclusion criteria for RCTs in PsABio.** An oligoarticular phenotype of the disease (<5 joints involved) was observed in 58.2% patients in PsABio, and overall, 408 of 930 (44%) PsABio participants would not have fulfilled the SJC and TJC requirement of ≥3 for each as is the case in most RCTs (Supplementary Table S4).

## Discussion

This study brings important information on PsA patient profiles included in RCTs and in routine clinical practice. In this metanalysis of 10 phase III RCTs of bDMARDs in PsA, patients had a highly active musculoskeletal disease, as reflected by a pooled mean SJC of 11.8 and TJC of 21.5, with frequent enthesitis (64.7%) and dactylitis (37.7%), and active skin psoriasis, with a vast majority (62.2%) having a BSA>3%. In contrast, in the real-life PsABio study of 930 patients over the same timeframe, although demographic data were similar, musculoskeletal disease activity was much lower (mean SJC 5.7, TJC 11.9, 48.2% of enthesitis and 19.8% of dactylitis), as was skin disease (46% had very limited psoriasis). On the other hand, PhGA and disease impact, as assessed through patient-reported outcomes, were high and comparable between RCTs and the real-world data study, while CRP was statistically significantly higher in PsABio, suggesting that CRP may play a role in the decision to start a bDMARD therapy in clinical practice. These findings emphasize the need for caution when applying results from RCTs to usual care, in terms of generalizability. They also confirm the physicians' gestalt when prescribing bDMARDs in usual practice, since although joint counts were lower in PsABio, other markers indicated those patients were indeed in need of a bDMARD.

This study has strengths and weaknesses. We only included trials published 2015-2020, to align with the timeframe of PsABio. This study did not include for the literature review a formal risk of bias assessment. However, such an assessment is not standard in the context of scoping reviews, which aim to map available evidence rather than provide an assessment of management options (8). Given that our meta-analysis is not based on individual patient data, the conclusions are only applicable at the group level. We could not, for example, separate and compare bDMARD naive and bDMARD experienced groups in both settings, though such a comparison would have been of interest. Also, we did not include data on axial disease or comorbidities, as they were not uniformly described among the different studies. For real-world data, we only relied on a single data source, the PsABio study, which might restrict the scope of our analysis, as it may not capture the diversity of patient populations in usual practice. However, PsABio is one of the largest clinical practice studies in PsA, providing data on more than 900 participants starting a bDMARD, in a multinational setting. Further research in a broader population and/or in other observational studies would be useful to confirm our findings.
Disease activity was high in RCTs. Although it was much lower in PsABio than RCTs, it was still remarkably high for routine clinical practice with a mean of 6 swollen and 12 tender joints. The higher disease activity identified in this metanalysis of RCTs aligns with previous research, indicating that evidence-based knowledge of PsA treatments mainly focuses on polyarticular disease, which only accounts for a subgroup of PsA (4,5). Patients in PsABio were more often oligoarticular but were apparently as much in need of a bDMARD as those in the RCTs, as shown by the fact that 50% had already received another bDMARD before, while this was the case in less than 30% of RCTs patients. The lower joint counts observed in PsABio patients is interesting when considering that countries may have rules for minimal disease activity when starting a bDMARD, and in PsABio (an observational study) the drugs were not provided in the context of the study, nor was there a wash-out period. Despite the overall lower disease activity and similar disease duration, PsABio patients may have had more refractory disease than most of the RCT patients, which is also reflected by a similar burden according to patient reported outcomes and also by a relatively high PhGA score and elevated CRP.

Despite differences in joint counts and enthesitis/dactylitis between RCTs and the observational study, patients with PsA reported a high and similar disease impact in both settings. This may point towards a disconnect between clinical examination and patient-reported complaints, as previously indicated in 30-70% of PsA patients (20,21). In the present study, widespread pain was not assessed – it is possible that differences in rates of this comorbidity may have influenced our findings. On the other hand, PhGA was statistically significantly higher in RCTs (60mm) than in PsABio (54mm). The difference was moderate and numerically not nearly as far apart between the studied groups as joint counts, indicating that physicians regarded the disease activity within PsABio as quite significant. Also, CRP was lower in RCTs than PsABio, thus patient assessment is aligned in some ways with some of the markers of local and systemic disease activity. Both of these elements go in the direction of supporting the need for bDMARDs in the PsABio patients, thus confirming the physician's decision.

Skin disease was much more prevalent and severe in RCTs versus in the PsABio study. This is likely due to the requirement in six of the evaluated studies of the presence of a minimum of skin involvement, while this was not the case in PsABio. However, the observation of a low frequency of major skin involvement in this real-world setting lends further support to previous findings that psoriasis is relatively mild in clinical practice in patients with PsA.

Data from clinical practice are increasingly being used to supplement those from RCTs in improving our understanding of response to treatment in PsA. The selection criteria of RCTs of bDMARDs in PsA may not always allow the inclusion of all patients who would benefit from these treatments (4). In the PsABio registry, almost half of the cohort could not have been included in RCTs, confirming other studies where lack of polyarticular disease was also often reported as a limiting factor for inclusion (3,22). It is currently unclear if treatment effectiveness and drug survival are similar in patients with PsA eligible or not for RCTs (22). Of note, the present analyses did not compare the efficacy of drugs between the two settings (observational study versus RCTs) – thus we cannot conclude on the relative ‘usefulness’ of drug prescriptions in these two settings. Although recently, an
evolution of the patient population considered for RCTs has been observed, with inclusion of patients with earlier and less severe disease (5), the present findings indicate that subanalyses of patients who are more similar to the ones in practice (e.g., oligoarticular patients) are needed, and should be pre-specified in the design of RCTs.

In summary, our study demonstrated that PsA patients in routine practice had mild/moderate joint disease and often limited skin psoriasis, leading to lower overt joint disease, while CRP and PhGA were high. Although they differed significantly from patients eligible for and included in RCTs, these findings are in line with the decision for a bDMARD therapy in PsABio. RCTs populations are not fully representative of routine care populations; future studies should address the population of patients ineligible for RCTs, but still at need for effective therapy.

## Acknowledgements:

The authors thank the PsABio investigators and patients.

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21. Michelsen B, Kristianslund EK, Hammer HB, Fagerli KM, Lie E, Wierød A, et al. Discordance between tender and swollen joint count as well as patient's and evaluator's global assessment may reduce likelihood of remission in patients with rheumatoid arthritis and psoriatic arthritis: Data from the prospective multicentre NOR-DMARD stu. Ann Rheum Dis 2017;76:708-11.

22. Palsson O, Love TJ, Gunnarsdottir AI, Gunnarsson PS, Runarsdottir EE, Krogh NS, et al. Patients with psoriatic arthritis who are not eligible for randomised controlled trials for TNF inhibitors have treatment response and drug survival similar to those who are eligible. RMD Open 2019;5:1-7.
<table><caption>**Table 1.** Baseline characteristics of participants in the 10 selected phase III RCTs of bDMARDs.</caption><thead><tr><th></th><th>FUTUR E 1<br>(secukin umab)</th><th>FUTUR E 2<br>(secukin umab)</th><th>GO-VIBR ANT<br>(golimu mab)</th><th>ASTR AEA<br>(abatac ept)</th><th>SPIRI T-P1<br>(ixekizu mab)</th><th>SPIRI T-P2<br>(ixekizu mab)</th><th>FUTUR E 5<br>(secukin umab)</th><th>SEAM -PSA<br>(etaner cept)</th><th>DISCO VER 1<br>(guselk umab)</th><th>DISCO VER 2<br>(guselk umab)</th><th>RCT s<br>Pool ed mea n / % (95 %CI)</th></tr></thead><tbody><tr><td>Total number of enrolled patients</td><td>606</td><td>397</td><td>480</td><td>424</td><td>417</td><td>363</td><td>996</td><td>851</td><td>381</td><td>739</td><td>5654</td></tr><tr><td>Age (years), mean (SD)</td><td>49.0 (11.7)</td><td>48.0 (12.0)</td><td>46.2 (11.9)</td><td>50.4 (11.0)</td><td>49.5 (11.9)</td><td>51.9 (12.0)</td><td>48.8 (12.4)</td><td>48.4 (13.1)</td><td>48.4 (11.4)</td><td>45.7 (11.7)</td><td>48.6 (41.3 - 56.0)</td></tr><tr><td>Female sex, n (%)</td><td>330 (54.5)</td><td>205 (51.6)</td><td>231 (48.1)</td><td>233 (55.0)</td><td>225 (54.0)</td><td>194 (53.4)</td><td>496 (49.8)</td><td>432 (50.8)</td><td>186 (48.8)</td><td>351 (47.5)</td><td>50.7 (48.1 - 53.2)</td></tr><tr><td>Weight (kg), mean (SD)</td><td>82.9 (20.4)</td><td>87.1 (19.6)</td><td>NR</td><td>NR</td><td>85.6 (20.9)</td><td>88.7 (21.6)</td><td>83.4 (19.2)</td><td>NR</td><td>86.1 (18.8)</td><td>84.3 (19.5)</td><td>85.4 (70.6 - 100.1)</td></tr><tr><td>BMI, kg/m², mean (SD)</td><td>NR</td><td>NR</td><td>NR</td><td>31.0 (6.5)</td><td>30.0 (8.5)</td><td>30.9 (7.2)</td><td>NR</td><td>30.3 (6.8)</td><td>NR</td><td>NR</td><td>30.6 (23.6 - 37.6)</td></tr><tr><td>Time since PsA diagnosis (years), mean (SD)</td><td>NR</td><td>NR</td><td>5.8 (6.0)</td><td>8.5 (8.2)</td><td>6.7 (7.2)</td><td>10.0 (8.1)</td><td>6.6 (7.3)</td><td>3.2 (6.3)</td><td>6.7 (6.6)</td><td>5.5 (5.7)</td><td>6.3 (1.6-10.9)</td></tr><tr><td>MTX ongoing</td><td>368</td><td>185</td><td>336</td><td>256</td><td>226</td><td>149</td><td>499</td><td>0 (0)</td><td>211</td><td>443</td><td>49.6</td></tr></tbody></table>
<table><tbody><tr><td>at baseline, n (%)</td><td>(60.7)</td><td>(46.6)</td><td>(70.0)</td><td>(60.4)</td><td>(54.2)</td><td>(41.0)</td><td>(50.1)</td><td>(55.4)</td><td>(59.9)</td><td>(37.1 - 62.1)</td></tr><tr><td>Previous bDMARDs, n (%)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>None</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td>72.0 (51.3 - 91.8)</td></tr><tr><td>1</td><td>428 (70.6)</td><td>258 (65.0)</td><td>480 (100)</td><td>165 (38.9)</td><td>417 (100)</td><td>0 (0)</td><td>701 (70.4)</td><td>851 (100)</td><td>263 (69.0)</td><td>739 (100)</td></tr><tr><td>≥2</td><td>109 (18.0)</td><td>79 (19.9)</td><td>0 (0)</td><td>186 (43.9)</td><td>0 (0)</td><td>235 (64.7)</td><td>197 (19.8)</td><td>0 (0)</td><td>102 (26.8)</td><td>0 (0)</td></tr><tr><td></td><td>69 (11.4)</td><td>60 (15.1)</td><td>0 (0)</td><td>73 (17.2)</td><td>0 (0)</td><td>128 (35.3)</td><td>98 (9.8)</td><td>0 (0)</td><td>16 (4.2)</td><td>0 (0)</td></tr><tr><td>Glucocorticoids at baseline</td><td>95 (15.7)</td><td>81 (20.4)</td><td>133 (27.7)</td><td>107 (25.2)</td><td>NR</td><td>NR</td><td>168 (16.9)</td><td>NR</td><td>54 (14.2)</td><td>145 (19.6)</td></tr><tr><td>SJC 0-66 joints, mean (SD)</td><td>13.4 (11.2)†</td><td>11.5 (9.4)†</td><td>14.0 (8.3)</td><td>11.6 (7.5)</td><td>11.0 (7.4)</td><td>12.3 (10.1)</td><td>11.5 (10.1)†</td><td>11.9 (9.5)</td><td>9.9 (7.4)</td><td>12.3 (7.2)</td></tr><tr><td>TJC 0-68 joints, mean (SD)</td><td>24.1 (17.3)‡</td><td>22.5 (17.0)‡</td><td>25.6 (14.1)</td><td>20.2 (13.3)</td><td>20.1 (13.4)</td><td>23.3 (15.9)</td><td>21.0 (15.8)‡</td><td>19.9 (14.9)</td><td>19.2 (14.0)</td><td>21.3 (12.8)</td></tr><tr><td>Enthesitis, n (%)</td><td>372 (61.4)</td><td>253 (63.7)</td><td>366 (76.3)</td><td>272 (64.2)</td><td>242 (58.0)</td><td>221 (60.9)</td><td>602 (60.4)</td><td>57 (67.7)</td><td>222 (58.3)</td><td>506 (68.5)</td></tr><tr><td>Leeds Enthesitis Index, mean (SD)</td><td>NR</td><td>3.1 (1.7)</td><td>3.1 (1.6)</td><td>NR</td><td>2.9 (1.7)</td><td>2.9 (1.6)</td><td>NR</td><td>NR</td><td>2.8 (1.6)</td><td>2.8 (1.6)</td></tr><tr><td>Dactylitis, n (%)</td><td>324 (53.5)</td><td>137 (34.5)</td><td>258 (53.8)</td><td>111 (26.2)</td><td>157 (37.6)</td><td>62 (17.1)</td><td>389 (39.1)</td><td>284 (33.4)</td><td>142 (37.3)</td><td>331 (44.8)</td></tr></tbody></table>
<table><tr><td>Dactylitis count, mean (SD)</td><td>NR</td><td>3.5 (3.6)</td><td>9.6 (9.7)</td><td>NR</td><td>NR</td><td>NR</td><td>NR</td><td>NR</td><td>8.1 (10.0)</td><td>8.3 (9.5)</td><td>5.0 (-0.9 to 10.9)</td></tr><tr><td>BSA %, mean (SD)</td><td>NR</td><td>NR</td><td>NR</td><td>NR</td><td>NR</td><td>11.1 (16.4)</td><td>NR</td><td>NR</td><td>11.4 (16.4)</td><td>13.3 (17.3)</td><td>17.4 (20.3)</td><td>12.9 (-4.16 to 29.9)</td></tr><tr><td>BSA ≥3%, n (%)</td><td>325 (53.6)</td><td>192 (48.4)</td><td>394 (82.1)</td><td>294 (69.3)</td><td>267 (69.5)</td><td>NR</td><td>514 (51.6)</td><td>548 (64.4)</td><td>NR</td><td>NR</td><td>62.2 (54.0 - 70.3)</td></tr><tr><td>PASI score (0-72), mean (SD)</td><td>13.8 (11.4) ||</td><td>NR</td><td>9.9 (9.4) ||</td><td>7.3 (7.9) ||</td><td>6.1 (6.9)</td><td>5.9 (7.6)</td><td>NR</td><td>NR</td><td>8.5 (9.6)</td><td>9.9 (11.1)</td><td>8.0 (1.5-14.4)</td></tr><tr><td>Psoriatic nail disease, n (%)</td><td>NR</td><td>NR</td><td>NR</td><td>NR</td><td>289 (69.3)</td><td>236 (65.0)</td><td>NR</td><td>NR</td><td>NR</td><td>NR</td><td>67.6 (59.8 - 75.3)</td></tr><tr><td>Physician's global assessment of disease activity (VAS 0-100mm), mean (SD)</td><td>56.4 (18.6)</td><td>56.5 (16.5)</td><td>63.0 (16.5)</td><td>54.4 (19.2)</td><td>56.9 (18.9)</td><td>61.3 (19.4)</td><td>55.9 (19.3)</td><td>NR</td><td>62.3 (16.7)</td><td>66.0 (15.3)</td><td>59.7 (48.1 - 71.2)</td></tr><tr><td>Patient-assessed global disease activity (VAS 0-100mm), mean (SD)</td><td>55.6 (22.8)</td><td>60.0 (19.2)</td><td>64.0 (20.0)</td><td>61.8 (23.1)</td><td>61.4 (20.2)</td><td>65.5 (20.8)</td><td>53.9 (22.7)</td><td>NR</td><td>62.3 (20.7)</td><td>64.7 (18.7)</td><td>61.4 (47.8 - 74.9)</td></tr><tr><td>Patient-reported pain (VAS 0-100mm), mean</td><td>55.8 (22.5)</td><td>57.3 (20.5)</td><td>63.5 (20.5)</td><td>64.3 (22.7)</td><td>58.9 (20.9)</td><td>63.5 (20.8)</td><td>54.3 (23.9)</td><td>NR</td><td>59.0 (21.0)</td><td>62.7 (19.3)</td><td>60.1 (46.3 - 74.0)</td></tr></table>
<table><tr><td>(SD)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>HAQ-DI score, mean (SD)</td><td>1.2 (0.7)</td><td>1.2 (0.6)</td><td>1.3 (0.6)</td><td>1.3 (0.7)</td><td>1.2 (0.6)</td><td>1.2 (0.6)</td><td>1.3 (0.6)</td><td>1.2 (0.0)</td><td>1.1 (0.6)</td><td>1.3 (0.6)</td><td>1.2 (1.1-1.3)</td></tr><tr><td>CRP (mg/dL), mean (SD) (normal range: 0-0.5)</td><td>NR</td><td>NR</td><td>1.9 (1.7)</td><td>1.4 (2.6)*</td><td>1.4 (2.2)*</td><td>1.4 (2.4)*</td><td>NR</td><td>NR</td><td>0.7 (0.9)</td><td>1.2 (1.4)</td><td>1.1 (-0.1 to 2.3)</td></tr></table>

Studies are presented by date of publication.

All the patients included in each RCT (whatever the treatment arm) were analysed together. When the data were presented only by treatment arm, weighted means and SD were calculated for the continuous data, and percentages were recalculated for the discrete data.

Heterogeneity ranged from 0 to 100% across the binary outcomes, while all the continuous outcomes showed an I2 value of 0% (data not shown).

bDMARD, biological disease-modifying antirheumatic drug; BMI, body mass index; BSA, body surface area; CI, confidence interval; CRP, C-reactive protein; HAQ-DI, Health Assessment Questionnaire-Disability Index; MTX, methotrexate; NR, not reported; PASI, Psoriasis Area and Severity index; PsA, psoriatic arthritis; RCTs, randomised controlled trials; SD, standard deviation; SJC, swollen joint count; TJC, tender joint count; VAS, visual analogue scale.

<footnote>†SJC (76 joints).</footnote>

<footnote>‡TJC (78 joints).</footnote>

<footnote>||PASI was only assessed in patients in whom psoriasis affected at least 3% of the body-surface area.</footnote>

<footnote>*CRP originally indicated as mg/L and converted into mg/dL.</footnote>
<table><caption>**Table 2.** Comparison of baseline characteristics from a real-world study (PsABio) and pooled data from 10 bDMARD phase III RCTs.</caption><thead><tr><th></th><th>RCTs*</th><th>PsABio**</th><th>p-value</th></tr></thead><tbody><tr><td>Total number of patients starting treatment</td><td>5654</td><td>930</td><td>-</td></tr><tr><td>Age (years)</td><td>48.6 (41.3-56.0)</td><td>49.7 (12.5)</td><td>&lt;0.001</td></tr><tr><td>Female sex</td><td>50.7 (48.1-53.2)</td><td>55.2 (51.3)</td><td>0.01</td></tr><tr><td>Weight (kg)</td><td>85.4 (70.6-100.1)</td><td>80.9 (17.0)</td><td>&lt;0.001</td></tr><tr><td>BMI, kg/m<sup>2</sup></td><td>30.6 (23.6-37.6)</td><td>28.1 (5.8)</td><td>&lt;0.001</td></tr><tr><td>Time since PsA diagnosis (years)</td><td>6.3 (1.6-10.9)</td><td>6.8 (7.4)</td><td>0.03</td></tr><tr><td>MTX ongoing at baseline</td><td>49.6 (37.1-62.1)</td><td>35.7 (332)</td><td>&lt;0.001</td></tr><tr><td>Previous bDMARDs</td><td></td><td></td><td></td></tr><tr><td>None</td><td>72.0 (51.3-91.8)</td><td>50.4 (469)</td><td>&lt;0.001</td></tr><tr><td>1</td><td>19.4 (5.6-31.7)</td><td>33.0 (307)</td><td>&lt;0.001</td></tr><tr><td>≥2</td><td>8.6 (2.3-14.3)</td><td>16.6 (154)</td><td>&lt;0.001</td></tr><tr><td>SJC</td><td>11.8 (6.5-17.1)</td><td>5.7 (7.6)</td><td>&lt;0.001</td></tr><tr><td>TJC</td><td>21.5 (12.5-30.6)</td><td>11.9 (11.6)</td><td>&lt;0.001</td></tr><tr><td>Enthesitis</td><td>64.7 (61.1-68.5)</td><td>48.2 (448)</td><td>&lt;0.001</td></tr><tr><td>Leeds Enthesitis Index</td><td>2.9 (1.6-4.2)</td><td>1.2 (1.6)</td><td>&lt;0.001</td></tr><tr><td>Dactylitis</td><td>37.7 (30.6-44.7)</td><td>19.8 (184)</td><td>&lt;0.001</td></tr><tr><td>Dactylitis count</td><td>5.0 (-0.9 to 10.9)</td><td>3.1 (3.1)</td><td>&lt;0.001</td></tr><tr><td>BSA ≥3%</td><td>62.2 (54.0-70.3)</td><td>54.0 (442/819)<sup>‡</sup></td><td>&lt;0.001</td></tr><tr><td>PASI score (0-72)</td><td>8.0 (1.5-14.4)</td><td>NR</td><td>-</td></tr><tr><td>Psoriatic nail disease</td><td>67.6 (59.8-75.3)</td><td>40.1 (373)</td><td>&lt;0.001</td></tr><tr><td>Physician's global assessment of disease activity (VAS 0–100mm)</td><td>59.7 (48.1-71.2)</td><td>54.1 (20.1)</td><td>&lt;0.001</td></tr><tr><td>Patient-assessed global disease activity (VAS 0–100mm)</td><td>61.4 (47.8-74.9)</td><td>60.7 (23.7)</td><td>0.45</td></tr><tr><td>Patient-reported pain (VAS 0–100mm)</td><td>60.1 (46.3-74.0)</td><td>60.7 (23.9)</td><td>0.71</td></tr><tr><td>HAQ-DI score</td><td>1.2 (1.1-1.3)</td><td>1.1 (0.7)</td><td>&lt;0.001</td></tr><tr><td>CRP (mg/dL) - (normal range: 0–</td><td>1.1 (-0.1 to 2.3)</td><td>1.4 (2.8)</td><td>0.002</td></tr></tbody></table>
0.5)

*For RCTs, continuous data are indicated as pooled mean (95% CI) and discrete data are indicated as percentage (95% CI).

**For PsABio, continuous data are indicated as mean (SD) and discrete data are indicated as number (percentage).

‡ Total patients n=819. Data indicated as N/n (%)

bDMARD, biological disease-modifying antirheumatic drug; BMI, body mass index; BSA, body surface area; CI, confidence interval; CRP, C-reactive protein; HAQ-DI, Health Assessment Questionnaire-Disability Index; MTX, methotrexate; NR, not reported; PASI, Psoriasis Area and Severity index; PsA, psoriatic arthritis; RCTs, randomised controlled trials; SD, standard deviation; SJC, swollen joint count; TJC, tender joint count; VAS, visual analogue scale.
**Figure 1.** Disease activity assessments at baseline in patients with PsA included in phase III RCTs of bDMARDs published between 2015-2020.

A. Swollen Joint Counts. B. Tender Joint Counts. C. Presence of enthesitis. D. Psoriasis extension, Body Surface Area>3%.

<figure><img src="image_3.png" /></figure>

C. Enthesitis

<figure><img src="image_4.png" /></figure>

<figure><img src="image_5.png" /></figure>

D. BSA>3%

<figure><img src="image_6.png" /></figure>

PsA, psoriatic arthritis; RCTs, randomised controlled trials; bDMARD, biological disease-modifying antirheumatic drug; SJC, swollen joint counts; TJC, tender joint counts; BSA, body surface area.
Data Supplements

<figure><img src="image_7.png" /><figcaption>**Supplementary Figure S1.** Selection of phase III RCTs of bDMARDs in PsA published between 2015-2020.</figcaption></figure>
<table><caption>**Supplementary Table S2.** Study characteristics of 10 phase III RCTs of bDMARDs in PsA published between 2015-2020.</caption><thead><tr><th>References</th><th>Trial name (ClinicalTrials.gov identifier)</th><th>Year of publication</th><th>Recruitment period</th><th>Country/region</th><th>Number of centres</th><th>Overall n</th><th>Analysed drugs</th></tr></thead><tbody><tr><td>Mease PJ, et al. (10)</td><td>FUTURE 1 (NCT01392326)</td><td>2015</td><td>September 2011 – October 2012</td><td>Europe, North America, Asia, Latin America and Australia</td><td>104</td><td>606</td><td>Secukinumab</td></tr><tr><td>McInnes IB, et al. (11)</td><td>FUTURE 2 (NCT01752634)</td><td>2015</td><td>April 2013 – November 2013</td><td>Europe, North America, Asia and Australia</td><td>76</td><td>397</td><td>Secukinumab</td></tr><tr><td>Kavanaugh A, et al. (12)</td><td>GO-VIBRANT (NCT02181673)</td><td>2017</td><td>September 2014 – July 2016</td><td>Europe, North America and Asia</td><td>90</td><td>480</td><td>Golimumab</td></tr><tr><td>Mease PJ, et al. (13)</td><td>ASTRAEA (NCT01860976)</td><td>2017</td><td>June 2013 – April 2016</td><td>Europe, North America, Latin America, South Africa and Middle East</td><td>76</td><td>424</td><td>Abatacept</td></tr><tr><td>Mease PJ, et al. (14)</td><td>SPIRIT-P1 (NCT01695239)</td><td>2017</td><td>December 2012 – December 2014</td><td>Europe, North America and Asia</td><td>114</td><td>417</td><td>Ixekizumab</td></tr><tr><td>Nash P, et al. (15)</td><td>SPIRIT-P2 (NCT02349295)</td><td>2017</td><td>March 2015 – March 2016</td><td>North America, Europe, Asia and Australia</td><td>109</td><td>363</td><td>Ixekizumab</td></tr><tr><td>Mease PJ, et al. (16)</td><td>FUTURE 5 (NCT02404350)</td><td>2018</td><td>August 2015 – August 2017</td><td>Europe, North America, Asia and Latin America</td><td>169</td><td>996</td><td>Secukinumab</td></tr><tr><td>Mease PJ, et al. (17)</td><td>SEAM-PSA (NCT02376790)</td><td>2019</td><td>March 2015 – July 2017</td><td>North America, Europe, Latin America, Asia and South Africa</td><td>124</td><td>851</td><td>Etanercept</td></tr><tr><td>Deodhar A, et al. (18)</td><td>DISCOVER 1 (NCT03162796)</td><td>2020</td><td>August 2017 – August 2018</td><td>Europe, North America, Asia and Australia</td><td>86</td><td>381</td><td>Guselkumab</td></tr><tr><td>Mease PJ, et al. (19)</td><td>DISCOVER 2 (NCT03158285)</td><td>2020</td><td>July 2013 – August 2018</td><td>Europe, Asia and North America</td><td>118</td><td>739</td><td>Guselkumab</td></tr></tbody></table>

bDMARD, biological disease-modifying antirheumatic drug; RCTs, randomised controlled trials.
<figure><img src="image_8.png" /><figcaption>**Supplementary Figure S3.** Funnel plots for PsA characteristics at inclusion in phase III RCTs of bDMARDs published between 2015-2020. A. Tender Joint Counts. B. Swollen Joint Counts. C. Presence of enthesitis. D. Presence of dactylitis. E. Psoriasis extension ≥3% BSA. F. Physician Global Assessment. G. Patient Global Assessment. H. Pain. I. HAQ. J. C-reactive protein.</figcaption></figure>

PsA, psoriatic arthritis; RCTs, randomised controlled trials; bDMARD, biological disease-modifying antirheumatic drug; TJC, tender joint counts; SJC, swollen joint counts; BSA, body surface area; PhGA, physician global assessment; PGA, patient global assessment; HAQ, Health Assessment Questionnaire; CRP, C-reactive protein.
<table><caption>**Supplementary Table S4.** Inclusion and exclusion criteria for the selected phase III RCTs.</caption><thead><tr><th>Clinical trial (ClinicalTrials.gov identifier), Authors (publication year), and drug(s) assessed</th><th>Inclusion criteria</th><th>Exclusion criteria</th></tr></thead><tbody><tr><td><strong>FUTURE 1</strong><br>(NCT01392326)<br><br>Mease PJ, et al (2015) (10)<br><br>Assessed:<ul><li>Secukinumab 75 mg SC</li><li>Secukinumab 150 mg SC</li><li>Placebo</li></ul></td><td><ul><li>Adults aged ≥18 years</li><li>Diagnosis of PsA defined by CASPAR criteria</li><li>Active disease (SJC ≥3 and TJC ≥3) for at least 6 months, despite previous treatment with NSAIDs, cDMARDs or TNFi.</li><li>Concomitant oral corticosteroids (≤10 mg/day prednisone or equivalent) and MTX (≤25 mg/week) allowed (if dose was stable)</li><li>Rheumatoid factor and anti-CCP antibodies negative</li><li>Diagnosis of active plaque psoriasis, with at least one psoriatic plaque of ≥2cm diameter or nail changes consistent with psoriasis or documented history of plaque psoriasis</li></ul></td><td><ul><li>Previous treatment with more than 3 different TNFi.</li><li>Previous treatment with other bDMARDs other than TNFi.</li><li>Subjects taking high potency opioid analgesics</li><li>Presence of active inflammatory diseases other than PsA.</li><li>Active infection or history of ongoing, chronic or recurrent infections.</li><li>Evidence of a concurrent malignant process.</li><li>Pregnancy</li></ul></td></tr><tr><td><strong>FUTURE 2</strong><br>(NCT01752634)<br><br>Mclnnes IB, et al (2015) (11)<br><br>Assessed:<ul><li>Secukinumab 75 mg SC</li><li>Secukinumab 150 mg SC</li><li>Secukinumab 300 mg SC</li><li>Placebo</li></ul></td><td><ul><li>Adults aged ≥18 years</li><li>Diagnosis of PsA defined by CASPAR criteria</li><li>Active disease (SJC ≥3 and TJC ≥3), despite previous treatment with NSAIDs, cDMARDs or TNFi</li><li>Concomitant oral corticosteroids (≤10 mg/day prednisone or equivalent) and MTX (≤25 mg/week) allowed (if dose was stable for ≥2 weeks and ≥4 weeks before randomisation, respectively)</li><li>Patients with &lt;3 previous TNFi agents if inadequate response or treatment cessation due to safety or tolerability</li></ul></td><td><ul><li>Previous use of biological agent other than TNFi</li><li>Active inflammatory disease other than PsA</li><li>Active infection in the 2 weeks before randomisation, or history of ongoing, chronic or recurrent infections</li><li>History of malignant disease within past 5 years (excluding basal cell carcinoma or actinic keratosis, in-situ cervical cancer or non-invasive malignant colon polyps)</li><li>Pregnancy</li></ul></td></tr></tbody></table>
<table><tr><td>GO-VIBRANT<br/>(NCT02181673)<br/><br/>Kavanaugh A, et al<br/>(2017) (12)<br/><br/>Assessed:<br/>• Golimumab 2 mg/kg<br/>IV<br/>• Placebo</td><td><ul><li>Adults aged ≥18 years</li><li>Diagnosis of PsA defined by CASPAR criteria</li><li>Active PsA (SJC ≥5 and TJC ≥5 and a hsCRP ≥0.6 mg/dL) despite current or previous cDMARD therapy (≥3 months) and/or NSAID therapy (≥4 weeks), or demonstrated intolerance to these agents</li><li>Concomitant oral corticosteroids (≤10 mg/day prednisone or equivalent) and MTX (≤25 mg/week) allowed (if dose was stable for ≥2 weeks and ≥4 weeks before randomisation, respectively). NSAIDs permitted (if dose was stable ≥2 weeks before randomisation).</li></ul></td><td><ul><li>Previous bDMARD therapy for PsA</li><li>Other inflammatory diseases that might confound the evaluations of benefit of golimumab</li><li>Pregnancy, nursing, or planning a pregnancy or fathering a child while enrolled in the study or within 4 months after receiving the last administration of study agent</li><li>Have ever used cytotoxic drugs, including chlorambucil, cyclophosphamide, nitrogen mustard or other alkylating agents</li></ul></td></tr><tr><td>ASTRAEA<br/>(NCT01860976)<br/><br/>Mease PJ, et al (2017)<br/>(13)<br/><br/>Assessed:<br/>• Abatacept 125 mg SC<br/>• Placebo</td><td><ul><li>Adults aged ≥18 years</li><li>Diagnosis of PsA defined by CASPAR criteria</li><li>Active PsA (SJC ≥3 and TJC ≥3)</li><li>Active plaque psoriasis with ≥1 confirmed target lesion ≥2 cm</li><li>Inadequate response or intolerance to ≥1 cDMARD +/- TNFi</li><li>Concomitant use of methotrexate, leflunomide, sulfasalazine or hydroxychloroquine, NSAIDs and oral corticosteroids (&lt;10mg/day) is permitted, on a stable dose.</li></ul></td><td><ul><li>Subjects with guttate, pustular, or erythrodermic psoriasis</li><li>Prior exposure to more than 2 TNFi (due to inefficacy), Abatacept or other CTLA4 therapies, apremilast, ustekinumab, briakinumab.</li><li>Use of any of the following within 28 days or five half-lives prior to randomisation: Cyclosporine A, oral Tacrolimus, Mycophenolate Mofetil, Hydroxyurea, Fumaric Acid Esters, Paclitaxel, 6-Thioguanine, 6-Mercatopurine, or Tofacitinib</li><li>History of cancer within the last 5 years</li><li>History of any bacterial infection or herpes zoster within the last 60 days prior to screening</li><li>Evidence of active or latent bacterial, active viral, or serious latent viral infections at the time of enrollment</li><li>Subjects at risk for tuberculosis.</li></ul></td></tr><tr><td>SPIRIT-P1<br/>(NCT01695239)<br/><br/>Mease PJ, et al (2017)<br/>(14)<br/><br/>Assessed:<br/>• Adalimumab 40 mg SC Q2W<br/>• Ixekizumab 80 mg SC Q2W<br/>• Ixekizumab 80 mg SC Q4W<br/>• Placebo</td><td><ul><li>Adults aged ≥18 years</li><li>Diagnosis of PsA defined by CASPAR criteria ≥6 months</li><li>Active PsA (SJC ≥3 and TJC ≥3)</li><li>Either ≥1 PsA-related hand or foot joint erosion on centrally read X-rays or CRP &gt;6 mg/L</li><li>Presence of active psoriatic skin lesion or a personal history of plaque psoriasis</li></ul></td><td><ul><li>Current or historical use of biologic agents for treatment of psoriasis/PsA</li><li>Inadequate response to ≥4 bDMARDs</li><li>Current use of &gt;1 cDMARDs</li><li>Diagnosis of active inflammatory arthritic syndromes or spondyloarthropathies other than PsA</li><li>Prior treatment with IL-17 antagonists</li><li>Serious disorder or illness other than PsA</li><li>Serious infection within the past 3 months</li><li>Breastfeeding or nursing (lactating) women</li></ul></td></tr></table>
<table><tr><td><strong>SPIRIT-P2</strong><br>(NCT02349295)<br><br>Nash P, et al (2017)<br>(15)<br><br>Assessed:<ul><li>Ixekizumab SC Q4W</li><li>Ixekizumab SC Q2W</li><li>Placebo</li></ul></td><td><ul><li>Adults aged ≥18 years</li><li>Diagnosis of PsA defined by CASPAR criteria ≥6 months</li><li>Active PsA (SJC ≥3 and TJC ≥3)</li><li>Presence of active psoriatic skin lesion or a history of plaque psoriasis</li><li>Previously treated with ≥1 cDMARDs</li><li>Previous treatment with TNFi and inadequate response to up to 2 TNFi or TNFi intolerant</li></ul></td><td><ul><li>Current use of biologic agents for treatment of psoriasis/PsA</li><li>Inadequate response to >2 bDMARDs</li><li>Current use of >1 cDMARDs</li><li>Diagnosis of active inflammatory arthritic syndromes or spondyloarthropathies other than PsA</li><li>Prior treatment with IL-17 or IL-12/23 antagonists</li><li>Serious disorder or illness other than PsA</li><li>Serious infection within the past 3 months</li><li>Breastfeeding or nursing (lactating) women</li><li>History of malignant disease within the past 5 years</li></ul></td></tr><tr><td><strong>FUTURE 5</strong><br>(NCT02404350)<br><br>Mease PJ, et al (2018)<br>(16)<br><br>Assessed:<ul><li>Secukinumab 300 mg SC</li><li>Secukinumab 150 mg SC with loading dose</li><li>Secukinumab 150 mg SC without loading dose</li><li>Placebo</li></ul></td><td><ul><li>Adults aged ≥18 years</li><li>Diagnosis of PsA defined by CASPAR criteria</li><li>Moderate/severe PsA symptoms for ≥6 months: SJC ≥3 and TJC ≥3 despite ≥4 weeks of treatment with NSAIDs, or intolerance</li><li>Active or documented history of plaque psoriasis or psoriatic nail changes</li></ul></td><td><ul><li>Active/history of ongoing infection</li><li>Prior use of a biologic other than a TNFi</li><li>Use of ≥3 TNFi agents</li><li>Active inflammatory disease other than PsA</li></ul></td></tr><tr><td><strong>SEAM-PSA</strong><br>(NCT02376790)<br><br>Mease PJ, et al (2019)<br>(17)<br><br>Assessed:<ul><li>Etanercept 50 mg SC Q1W</li><li>MTX 20 mg oral Q1W</li><li>Placebo to etanercept</li><li>Placebo to MTX</li></ul></td><td><ul><li>Adults aged ≥18 years</li><li>Diagnosis of PsA defined by CASPAR criteria</li><li>Active disease (SJC ≥3 and TJC ≥3)</li><li>Active psoriatic skin lesion</li><li>Naïve to etanercept and any other biologic for treatment for PsA or psoriasis</li><li>No prior use of MTX for PsA</li><li>No history of tuberculosis</li><li>Negative test for tuberculosis, and hepatitis B and C</li></ul></td><td><ul><li>Known history of alcoholic hepatitis, non-alcoholic steatohepatitis or immunodeficiency syndromes, including HIV infection</li><li>Any active infection (including chronic or localised infections) for which anti-infectives were indicated within 4 weeks prior to first dose of investigational product</li><li>Serious infection (requiring hospitalisation or intravenous anti-infectives) within 8 weeks prior to the first dose of investigational product</li></ul></td></tr></table>
<table><tr><td>DISCOVER-1<br/>(NCT03162796)<br/><br/>Deodhar A, et al (2020)<br/>(18)<br/><br/>Assessed:<br/>• Guselkumab 100 mg<br/>SC Q4W<br/>• Guselkumab 100 mg<br/>SC Q8W<br/>• Placebo</td><td><ul><li>Adults aged ≥18 years</li><li>Diagnosis of PsA defined by CASPAR criteria ≥6 months</li><li>Active PsA (SJC ≥3 and TJC ≥3, CRP ≥0.3 mg/dL)</li><li>Have at least 1 of the PsA subsets: DIP joint involvement, polyarticular arthritis with absence of rheumatoid nodules, arthritis mutilans, asymmetric peripheral arthritis or spondylitis with peripheral arthritis</li><li>Active plaque psoriasis, with ≥1 psoriatic plaque of ≥2 cm diameter, or nail changes consistent with psoriasis or documented history of plaque psoriasis</li><li>Active PsA despite previous cDMARD (≥3 months/evidence of intolerance), apremilast (≥4 months/evidence of intolerance) and/or NSAID therapy (≥4 weeks/evidence of intolerance)</li><li>Previous treatment with ≤2 TNFi allowed (~30% of overall study population), with documented reasons for discontinuation</li></ul></td><td><ul><li>Other inflammatory diseases that might confound the evaluations of benefit of guselkumab therapy (e.g., RA, SLE, Lyme disease)</li><li>Use of >2 TNFi</li><li>Previous biologic treatment (other than TNFi agents)</li><li>Previous systemic immunosuppressants within 4 weeks of first study agent administration</li><li>Apremilast within 4 weeks prior to first administration of study agent</li><li>Previous tofacitinib, baricitinib, filgotinib, peficitinib (ASP015K), decernotinib (VX-509) or any other JAK inhibitor</li></ul></td></tr><tr><td>DISCOVER-2<br/>(NCT03158285)<br/><br/>Mease PJ, et al (2020)<br/>(19)<br/><br/>Assessed:<br/>• Guselkumab 100 mg<br/>SC Q4W<br/>• Guselkumab 100 mg<br/>SC Q8W<br/>• Placebo</td><td><ul><li>Adults aged ≥18 years</li><li>Diagnosis of PsA defined by CASPAR criteria ≥6 months</li><li>Active PsA (SJC ≥5 and TJC ≥5, CRP ≥0.6 mg/dL)</li><li>Have at least 1 of the PsA subsets: distal interphalangeal joint involvement, polyarticular arthritis with absence of rheumatoid nodules, arthritis mutilans, asymmetric peripheral arthritis, or spondylitis with peripheral arthritis</li><li>Active plaque psoriasis, with at least one psoriatic plaque of ≥ 2 cm diameter or nail changes consistent with psoriasis or documented history of plaque psoriasis</li><li>Active PsA despite previous cDMARD, apremilast, and/or NSAID therapy</li></ul></td><td><ul><li>Other inflammatory diseases that might confound the evaluations or benefit of guselkumab therapy (e.g., RA, SLE, Lyme disease)</li><li>Previous biologic treatment</li><li>Prior use of tofacitinib, baricitinib, filgotinib, peficitinib (ASP015K), decernotinib (VX-509), or any other JAK inhibitor</li><li>Use of any systemic immunosuppressants (e.g., azathioprine, cyclosporine, 6 thioguanine, mercaptopurine, mycophenolate mofetil, hydroxyurea, tacrolimus) within 4 weeks of the first administration of study agent</li><li>Use ≥ 2 cDMARDs</li><li>Use of apremilast within 4 weeks prior to the first administration of study agent</li></ul></td></tr></table>

Anti-CCP, anti-cyclic citrullinated peptides; bDMARD, biologic disease-modifying antirheumatic drug; CASPAR, Classification Criteria for Psoriatic Arthritis; cDMARD, conventional disease-modifying antirheumatic drug; CRP, C-reactive protein; CTLA-4, cytotoxic T-lymphocyte associated protein 4; DIP, distal interphalangeal; hsCRP, high-sensitivity C-reactive protein; HIV, human immunodeficiency virus; IL, interleukin; IV, intravenous; JAK, Janus kinase; MTX, methotrexate; NSAID, non-steroidal anti-inflammatory drug; PsA, psoriatic arthritis; Q1/2/4/8W, every 1/2/4/8 week(s); RA, rheumatoid arthritis; SC, subcutaneous; SJC, swollen joint count; SLE, systemic lupus erythematosus; TJC, tender joint count; TNFi, tumour necrosis factor inhibitor.