Influence of Anti-Psoriatic Biologic Therapies Targeting TNF-α and Interleukins 17 and 23 on the Risk of Development and Recurrence of Anogenital Warts: A Retrospective and Prospective Study With an Exploratory Component on HPV Vaccination Acceptability (CONDYPSO)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 600
- 试验地点
- 3
- 主要终点
- Incidence of anogenital warts
研究概览
简要总结
This study aims to assess the impact of anti-TNF-α, anti-IL-17, and anti-IL-23 biologic therapies on the risk of development or recurrence of anogenital warts (AGW) in patients with moderate to severe psoriasis. By modulating systemic and mucosal immunity, these treatments may alter host defenses against human papillomavirus (HPV) infections, which are responsible for AGW. In particular, inhibition of Th1 pathways (by anti-TNF-α) and Th17 pathways (by anti-IL-17 and anti-IL-23), both central to the antiviral response, may reduce local production of pro-inflammatory cytokines (such as IFN-γ, IL-17, and IL-22), decrease the activity of CD8+ cytotoxic T lymphocytes, and impair dendritic cell function, thereby compromising viral clearance at the genital mucosa.
AGW are a frequent and recurrent manifestation of HPV infection, and their incidence may be influenced by these immunomodulatory treatments.
The retrospective component will review cases already documented in medical records and analyze, to the extent permitted by available data, the same risk factors as in the prospective component, including history of sexually transmitted infections (STIs), risk behaviors, treatments used (systemic or topical), and time to onset or recurrence of AGW. This analysis will be conducted as a retrospective case-control study, matching each patient who developed AGW with one or more controls receiving biologics who did not develop AGW, in order to identify factors associated with their occurrence.
The prospective follow-up will assess, over 24 months, risk factors for occurrence or recurrence of AGW in patients with moderate to severe psoriasis, according to the treatment received: no treatment, topical treatment, systemic non-immunomodulatory treatment, or immunomodulatory treatment, including biologics. Acceptability of HPV vaccination will also be evaluated, at enrollment, in a subset of prospectively included adult patients without a known history or current clinical lesion of condyloma, HSIL, or HPV-induced carcinoma.
详细描述
Scientific Rationale
Anogenital warts (AGW) are a frequent manifestation of human papillomavirus (HPV) infection. Their course is generally benign, but they may cause significant discomfort and carry a high risk of recurrence, particularly in the context of immunomodulation.
Psoriasis is a chronic inflammatory skin disease affecting approximately 2-3% of the global population. Biologic therapies targeting IL-17 and IL-23, now widely used, profoundly modulate mucosal immunity by acting on the Th17 axis. This pathway plays a central role in defense against viral and fungal pathogens on mucosal surfaces, notably through the production of IL-17 and IL-22. Their inhibition leads to a decrease in these cytokines, which could theoretically impair local viral clearance, particularly with respect to HPV, thereby promoting persistence or recurrence of AGW.
Anti-TNF-α agents, long used in dermatology, also influence antiviral immunity by reducing the activity of cytotoxic CD8+ T lymphocytes and the production of IFN-γ, a key Th1 cytokine.
This rationale is supported by experimental data showing the essential role of Th1 and Th17 pathways, CD8+ lymphocytes, dendritic cells, and IFN-γ in the control of HPV infections.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Moderate to severe psoriasis (BSA > 10% or PASI > 10), prior to initiation of the current therapy at the time of inclusion
- •Planned dermatological follow-up for approximately 24 months, with no additional visits required by the study
- •Signed informed consent
排除标准
- •Severe immunosuppression not related to psoriasis or its therapy (concomitant treatment with major immunosuppressants, uncontrolled HIV infection, or other conditions inducing significant immunosuppression)
研究组 & 干预措施
Biologic therapies (Anti-TNF, Anti-IL-17, Anti-IL-23, including ustekinumab)
Psoriasis patients receiving biologic therapies. Observational follow-up of anogenital HPV-related outcomes (warts, recurrences, cytology, vaccination acceptability).
Other immunomodulators (methotrexate, cyclosporine, deucravacitinib, dimethyl fumarate)
Psoriasis patients receiving systemic immunomodulators other than biologics. Observational follow-up of anogenital HPV-related outcomes.
Other systemic non-immunomodulators (apremilast, acitretin)
Psoriasis patients receiving systemic therapies not primarily immunomodulatory. Observational follow-up of anogenital HPV-related outcomes.
Topical therapy only (topical corticosteroids, calcineurin inhibitors, phototherapy)
Psoriasis patients managed with topical therapy and/or phototherapy only. Observational follow-up of anogenital HPV-related outcomes.
Untreated psoriasis patients
Psoriasis patients currently not receiving any systemic or topical therapy. Observational follow-up of anogenital HPV-related outcomes.
结局指标
主要结局
Incidence of anogenital warts
时间窗: From enrollment until the end of the 2-year follow-up
To evaluate the incidence of anogenital warts (AW), including both new cases and recurrences, in patients with moderate-to-severe psoriasis, by comparing major therapeutic groups: biologic therapies (anti-TNF-α, anti-IL-17, anti-IL-23, ustekinumab), other immunomodulators (methotrexate, cyclosporine, deucravacitinib, dimethyl fumarate), non-immunomodulatory systemic therapies (apremilast, acitretin), topical therapies alone (topical corticosteroids, calcineurin inhibitors, phototherapy), or no treatment.
次要结局
- Characterization of AW cases under biologics(From enrollment until the end of the 2-year follow-up)
- Comparison of incidence and recurrence across treatments(From enrollment until the end of the 2-year follow-up)
- Risk factors for AW incidence and recurrence(From enrollment until the end of the 2-year follow-up)
- Impact of topical genital therapies(From enrollment until the end of the 2-year follow-up)
- HPV genotyping in prospective cases(After completion of the 2-year follow-up of enrolled patients)
- HPV vaccination acceptability(At enrollment)
研究者
Jonathan Krygier
Dr
Centre Hospitalier Universitaire Saint Pierre