Secukinumab treatment in new‐onset psoriasis: aiming to understand the potential for disease modification – rationale and design of the randomized, multicenter <scp>STEPI</scp>n study

Iversen, Lars; Eidsmo, Liv; Austad, J; Rie, Menno A. de; Osmancevic, Amra; Skov, Lone; Talme, Toomas; Bachmann, Ingeborg; Kerkhof, Peter van de; Ståhle, Mona; Banerjee, Rudrani; Oliver, Joseph B.; Fasth, Andreas E. R.; Frueh, Jennifer

doi:10.1111/jdv.14979

Cited by 50 publications

(51 citation statements)

References 69 publications

(167 reference statements)

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“…However, despite therapeutic effects, which sometimes go way beyond the respective molecules' half-lifes (91), all of these currently available therapies cannot prevent relapse, once they are stopped. Discussions to which extent such currently available therapies are disease-modifying, as we increasingly witness in the context of company-sponsored projects, e.g., in the field of psoriasis (92), seem therefore premature. Instead, remission might be a more appropriate term in this context.…”

Section: Therapeutic Perspectivesmentioning

confidence: 99%

Autoreactive T-Lymphocytes in Inflammatory Skin Diseases

Boehncke

Brembilla

2019

Front. Immunol.

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The presence of one or several autoantigen(s) and a response by the adaptive immune system are the key criteria to classify a pathology as an autoimmune disease. The list of entities fulfilling this criterion is currently growing in the light of recent advancements in the pathogenetic understanding of a number of important dermatoses. The role of autoreactive T-lymphocytes differs amongst these pathologies. While they are directly involved as effector cells attacking and sometimes killing their respective target in some diseases (e.g., vitiligo), they provide help to B-lymphocytes, which in turn produce the pathogenic autoreactive antibodies in others (pemphigus and pemphigoid). Atopic dermatits is a chimera in this regard, as there is evidence for both functions. Psoriasis is an example for an entity where autoantigens were finally identified, suggesting that at least a subgroup of patients should be classified as suffering from a true autoimmune rather than autoinflammatory condition. Identification of resident memory T-lymphocytes (T RM ) helped to understand why certain diseases relapse at the same site after seemingly effective therapy. Therefore, the in-depth characterization of autoreactive T-lyphocytes goes way beyond an academic exercise and opens the door toward improved therapies yielding durable responses. T RM are particularly suitable targets in this regard, and the clinical efficacy of some established and emerging therapeutic strategies such as the inhibition of Janus Kinase 3 or interleukin 15 may rely on their capacity to prevent T RM differentiation and maintenance. Research in this field brings us closer to the ultimate goal in the management of autoimmunity at large, namely resetting the immune system in order to restore the state of tolerance.

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Section: Therapeutic Perspectivesmentioning

confidence: 99%

Autoreactive T-Lymphocytes in Inflammatory Skin Diseases

Boehncke

Brembilla

2019

Front. Immunol.

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“…Nonetheless, the benefits of early aggressive strategy have been established in some inflammatory rheumatic diseases, including rheumatoid arthritis [27], Crohn’s disease [28], and ankylosing spondylosis [29]. A similar treatment algorithm of early aggressive intervention for psoriasis is still in its infancy, mainly because of the lack of apparent irreversible structural damage in psoriasis skin lesions [10]. The current treatment guidelines in psoriasis still recommend the use of biologics only in patients with moderate-to-severe psoriasis, but do take into consideration the quality of life issue in addition to the skin severity, i.e., PASI, BSA, and PGA [7, 30].…”

Section: Discussionmentioning

confidence: 99%

Remission Duration and Long-Term Outcomes in Patients with Moderate-to-Severe Psoriasis Treated by Biologics or Tofacitinib in Controlled Clinical Trials: A 15-Year Single-Center Experience

Huang

Tsai

2019

Dermatol Ther (Heidelb)

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Introduction: Relapse is common after treatment discontinuation for patients with moderate-to-severe psoriasis. The objective of this study was to understand the remission duration and long-term outcomes in psoriasis patients after biologic withdrawal. Methods: We retrospectively included the follow-up data of 184 patients with moderate-tosevere psoriasis after the end of 11 biologic or tofacitinib trials conducted between 2004 and 2016. Results: Among the 232 treatment courses, 95 achieved (psoriasis area and severity index) PASI 75 at the end of the studies. At 6 months after treatment discontinuation, the systemic treatment-free rates of our patients who entered the PRESTA,

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“…Possibly early active intervention with anti-IL-17 and anti-IL-23 may modify the long-term course of the disease. A controlled early intervention study is ongoing to find out whether early active intervention with secukinumab achieves disease modification (30). Furthermore, we have to find out which clinical characteristics and biomarkers can identify early on those patients in need for early intervention.…”

Section: Our Ambition In a Changing Landscape Of Psoriasis Treatmentsmentioning

confidence: 99%

Our ambition in a changing landscape of psoriasis treatments

Kerkhof

Feldman

2020

Journal of Dermatological Treatment

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Secukinumab treatment in new‐onset psoriasis: aiming to understand the potential for disease modification – rationale and design of the randomized, multicenter STEPIn study

Abstract: STEPIn is the first study to investigate whether early intensive treatment in new-onset psoriasis can modify the long-term natural course of the disease and thus become a novel treatment strategy for patients with psoriasis.

Cited by 50 publications

References 69 publications

Autoreactive T-Lymphocytes in Inflammatory Skin Diseases

Autoreactive T-Lymphocytes in Inflammatory Skin Diseases

Remission Duration and Long-Term Outcomes in Patients with Moderate-to-Severe Psoriasis Treated by Biologics or Tofacitinib in Controlled Clinical Trials: A 15-Year Single-Center Experience

Our ambition in a changing landscape of psoriasis treatments

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