Disease interception with interleukin-17 inhibition in high-risk psoriasis patients with subclinical joint inflammation—data from the prospective IVEPSA study

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Abstract

Background

A specific subset of psoriasis patients is characterized by subclinical inflammatory changes. These patients frequently present with arthralgia and have a higher risk to develop psoriatic arthritis (PsA). We hypothesized that IL-17A inhibition in this subset of patients can intercept the link between skin and joint disease and resolves pain and inflammatory changes.

Methods

Psoriasis, but no PsA, patients were included in the open prospective exploratory Interception in very early PsA (IVEPSA) study. Patients had to have nail or scalp involvement or a high psoriasis area severity index (PASI) (> 6) as well as inflammatory or erosive changes in MRI or CT. Patients received treatment with the anti-interleukin (IL)-17A antibody secukinumab over 24 weeks. Clinical assessments of skin and joint disease were done at baseline and after 12 and 24 weeks, MRI and CT at baseline and after 24 weeks.

Results

Twenty patients were included, 85% of them reporting arthralgia and 40% had tender joints at the examination. Eighty-three percent had at least one inflammatory lesion in the MRI, most of them synovitis/enthesitis. Skin disease (PASI: p < 0.002; BSA: p < 0.003) and arthralgia (VAS pain: p < 0.003) significantly improved after 24 weeks. Total PsAMRIS ( p = 0.005) and synovitis subscore ( p = 0.008) also significantly improved. Erosions and enthesiophytes did not progress, while bone mass in the distal radius significantly ( p = 0.020) increased after 24 weeks.

Conclusions

These data suggest that very early disease interception in PsA is possible leading to a comprehensive decline in skin symptoms, pain, and subclinical inflammation. IVEPSA therefore provides rationale for future early interventions with the concept to prevent the onset of PsA in high-risk individuals.

Trial registration

Trial registry name PSARTROS; trial registry number: NCT02483234; June 26, 2015.

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Most cited references 23

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In vivo assessment of trabecular bone microarchitecture by high-resolution peripheral quantitative computed tomography.

Stéphanie Boutroy, Mary Bouxsein, Francoise Munoz … (2005)

Assessment of trabecular microarchitecture may enhance the prediction of fracture risk and improve monitoring of treatment response. A new high-resolution peripheral quantitative computed tomography (HR-pQCT) system permits in vivo assessment of trabecular architecture and volumetric bone mineral density (BMD) at the distal radius and tibia with a voxel size of 82 microm3. We determined the short-term reproducibility of this device by measuring 15 healthy volunteers three times each. We compared HR-pQCT measurements in 108 healthy premenopausal, 113 postmenopausal osteopenic, and 35 postmenopausal osteoporotic women. Furthermore, we compared values in postmenopausal osteopenic women with (n = 35) and without previous fracture history (n = 78). We conducted a cross-sectional study in a private clinical research center. We took HR-pQCT measurements of the radius and tibia. Femoral neck and spine BMD were measured in postmenopausal women by dual-energy x-ray absorptiometry. Precision of HR-pQCT measurements was 0.7-1.5% for total, trabecular, and cortical densities and 2.5-4.4% for trabecular architecture. Postmenopausal women had lower density, trabecular number, and cortical thickness than premenopausal women (P < 0.001) at both radius and tibia. Osteoporotic women had lower density, cortical thickness, and increased trabecular separation than osteopenic women (P < 0.01) at both sites. Furthermore, although spine and hip BMD were similar, fractured osteopenic women had lower trabecular density and more heterogeneous trabecular distribution (P < 0.02) at the radius compared with unfractured osteopenic women. HR-pQCT appears promising to assess bone density and microarchitecture at peripheral sites in terms of reproducibility and ability to detect age- and disease-related changes.

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Incidence and clinical predictors of psoriatic arthritis in patients with psoriasis: a population-based study.

Sherine E Gabriel, Murat Icen, F. Wilson … (2009)

To determine the incidence and disease-specific predictors of clinically recognized psoriatic arthritis (PsA) in patients with psoriasis. We identified an incidence cohort of psoriasis subjects age >/=18 years diagnosed between January 1, 1970 and December 31, 1999 in a population-based setting. Psoriasis diagnoses were validated by confirmatory diagnosis in the medical record. Incident and clinically recognized PsA subjects were classified according to the Classification of Psoriatic Arthritis (CASPAR) criteria. Cox proportional hazards models were used to identify predictors of PsA within the psoriasis cohort. The psoriasis incidence cohort comprised 1,633 subjects. Of these, 40 were diagnosed with PsA concurrently with psoriasis and were excluded from analysis. The remaining 1,593 psoriasis subjects had a mean age of 43 years and 50% were men. Over 20,936 person-years of followup, 57 subjects were clinically recognized with new-onset PsA, with a cumulative incidence of 1.7% (95% confidence interval [95% CI] 1.0-2.3%), 3.1% (95% CI 2.2-4.1%), and 5.1% (95% CI 3.7-6.6%) at 5, 10, and 20 years following psoriasis incidence, respectively. Psoriasis features associated with higher risk of PsA were scalp lesions (hazard ratio [HR] 3.89, 95% CI 2.18-6.94), nail dystrophy (HR 2.93, 95% CI 1.68-5.12), and intergluteal/perianal lesions (HR 2.35, 95% CI 1.32-4.19). Calendar year was not associated with risk of PsA (P = 0.15), indicating that the likelihood of PsA in psoriasis subjects did not change over time. In this population-based study, <10% of patients with psoriasis developed clinically recognized PsA during a 30-year period. Psoriasis features associated with a higher likelihood of PsA were nail dystrophy, scalp lesions, and intergluteal/perianal psoriasis.

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Secukinumab improves active psoriatic arthritis symptoms and inhibits radiographic progression: primary results from the randomised, double-blind, phase III FUTURE 5 study

Philip Mease, Désirée van der Heijde, Robert Landewé … (2018)

Objectives To evaluate the effect of subcutaneous (s.c.) secukinumab, an interleukin-17A inhibitor, on clinical signs and symptoms and radiographic progression in patients with psoriatic arthritis (PsA). Methods Adults (n=996) with active PsA were randomised 2:2:2:3 to s.c. secukinumab 300 mg or 150 mg with loading dose (LD), 150 mg without LD or placebo. All groups received secukinumab or placebo at baseline, weeks 1, 2 and 3 and then every 4 weeks from week 4. The primary endpoint was the proportion of patients achieving an American College of Rheumatology 20 (ACR20) response at week 16. Results Significantly more patients achieved an ACR20 response at week 16 with secukinumab 300 mg with LD (62.6%), 150 mg with LD (55.5%) or 150 mg without LD (59.5%) than placebo (27.4%) (p<0.0001 for all; non-responder imputation). Radiographic progression, as measured by van der Heijde-modified total Sharp score, was significantly inhibited at week 24 in all secukinumab arms versus placebo (p<0.01 for 300 mg with LD and 150 mg without LD and p<0.05 for 150 mg with LD; linear extrapolation). Adverse event rates at week 24 were similar across treatment arms: 63.1% (300 mg with LD), 62.7% (150 mg with LD), 61.1% (150 mg without LD) and 62.0% (placebo). No deaths or new safety signals were reported. Conclusion S.c. secukinumab 300 mg and 150 mg with and without LD significantly improved clinical signs and symptoms and inhibited radiographic structural progression versus placebo at week 24 in patients with PsA. Trial registration number NCT02404350; Results.

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Author and article information

Contributors

Georg Schett: +49 9131-85 39131 , georg.schett@uk-erlangen.de

Journal

Journal ID (nlm-ta): Arthritis Res Ther

Journal ID (iso-abbrev): Arthritis Res. Ther

Title: Arthritis Research & Therapy

Publisher: BioMed Central (London )

ISSN (Print): 1478-6354

ISSN (Electronic): 1478-6362

Publication date (Electronic): 26 July 2019

Publication date PMC-release: 26 July 2019

Publication date (Print): 2019

Volume: 21

Electronic Location Identifier: 178

Affiliations

[1 ]ISNI 0000 0001 2107 3311, GRID grid.5330.5, Department of Internal Medicine 3 – Rheumatology and Immunology, , Friedrich-Alexander-University Erlangen-Nurnberg (FAU) and Universitaetsklinikum Erlangen, ; Ulmenweg 18, 91054 Erlangen, Germany

[2 ]ISNI 0000 0001 2107 3311, GRID grid.5330.5, Department of Dermatology, , Friedrich-Alexander University Erlangen-Nurnberg (FAU) and Universitaetsklinikum Erlangen, ; Erlangen, Germany

[3 ]ISNI 0000 0001 0617 3250, GRID grid.419802.6, Sektion Rheumatologie, Sozialstiftung Bamberg, ; Bamberg, Germany

Article

Publisher ID: 1957

DOI: 10.1186/s13075-019-1957-0

PMC ID: 6659205

PubMed ID: 31349876

SO-VID: 716e2948-864d-4d0d-94e0-88fbdc117f28

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 6 March 2019

Date accepted : 8 July 2019

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100002347, Bundesministerium für Bildung und Forschung;

Award ID: project Metarthros

Funded by: FundRef http://dx.doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft;

Award ID: CRC1181 (project INST 90/925-1)

Award ID: FOR 2886 (project SCHE 1583/15-1)

Award ID: project SCHE 1583/14-1

Funded by: FundRef http://dx.doi.org/10.13039/501100010767, Innovative Medicines Initiative;

Award ID: RTCure (115142)

Funded by: Foundation for Research in Rheumatology

Funded by: FundRef http://dx.doi.org/10.13039/100008792, Novartis Pharma;

Custom metadata

ScienceOpen disciplines: Orthopedics

Keywords: psoriasis,psoriatic arthritis,interleukin-17,magnetic resonance imaging

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ScienceOpen disciplines: Orthopedics

Keywords: psoriasis, psoriatic arthritis, interleukin-17, magnetic resonance imaging

Disease interception with interleukin-17 inhibition in high-risk psoriasis patients with subclinical joint inflammation—data from the prospective IVEPSA study

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Abstract

Background

Methods

Results

Conclusions

Trial registration

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Karger: Neurology and Neuroscience

Most cited references 23

In vivo assessment of trabecular bone microarchitecture by high-resolution peripheral quantitative computed tomography.

Incidence and clinical predictors of psoriatic arthritis in patients with psoriasis: a population-based study.

Secukinumab improves active psoriatic arthritis symptoms and inhibits radiographic progression: primary results from the randomised, double-blind, phase III FUTURE 5 study

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