Guidelines How to Integrate Surgery and Targeted Therapy with Biologics for the Treatment of Hidradenitis Suppurativa: Delphi Consensus Statements from an Italian Expert Panel.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent and painful nodules and abscesses in intertriginous skin areas, which can progress to sinus tract formation, tissue destruction, and scarring. HS is highly debilitating and severely impairs the psychological well-being and quality of life of patients. The therapeutic approach to HS is based on medical therapy and surgery. First-line medical therapy includes topical antibiotics, systemic antibiotics, and biologics. Main surgical procedures include deroofing, local excision, and wide local excision. Despite the availability of multiple therapeutic options, the rates of disease recurrence and progression continue to be high. In recent years, the possibility of combining biologic therapy and surgery has raised considerable interest. In a clinical trial, the perioperative use of adalimumab has been associated with greater response rates and improved inflammatory load and pain, with no increased risk of postoperative infectious complications. However, several practical aspects of combined biologic therapy and surgery are poorly defined. In June 2022, nine Italian HS experts convened to address issues related to the integration of biologic therapy and surgery in clinical practice. To this purpose, the experts identified 10 areas of interest based on published evidence and personal experience: (1) patient profiling (diagnostic criteria, disease severity classification, assessment of response to treatment, patient-reported outcomes, comorbidities); (2) tailoring surgery to HS characteristics; (3) wide local excision; (4) presurgery biologic treatment; (5) concomitant biologic and surgical treatments; (6) pre- and postsurgery management; (7) antibiotic systemic therapy; (8) biologic therapy after radical surgery; (9) management of adverse events to biologics; and (10) management of postoperative infectious complications. Consensus between experts was reached using the Estimate-Talk-Estimate method (Delphi Method). The statements were subsequently presented to a panel of 27 HS experts from across Italy, and their agreement was assessed using the UCLA Appropriateness Method. This article presents and discusses the consensus statements.

Adalimumab in the management of psoriasis and psoriatic arthritis: Results from a Delphi investigation.

Background and Objectives: Psoriasis (PsO) and psoriatic arthritis (PsA) are often undertreated and require a multidisciplinary approach. In recent years, patent expiration has allowed the introduction of tumor necrosis factor inhibitor (anti-TNF) biosimilars, which have stimulated a significant increase in the use of biological therapies. This article reports the findings of a multidisciplinary approach to achieve a consensus on the use of adalimumab in patients with PsO or PsA. Methods: A voting panel of 36 Italian dermatologists and rheumatologists were chosen by eight Italian clinicians (the Board), to provide a consensus on the real-world management of PsO and PsA with adalimumab using the Delphi Method, comprising three survey rounds. Twelve statements were defined by the Board and submitted to the panel (rating scale 1-7). Results: Clinicians reached a wide consensus on the effectiveness (score 6-7: 67%) and long-term efficacy (6-7: 100%) of adalimumab in all clinical forms of PsO and PsA, including pediatric patients (6-7: 85%). Considering cost-effectiveness and safety, adalimumab is suggested as a first-line treatment in patients with enthesitis, predominant peripheral arthritis, axial involvement or associated inflammatory bowel disease (IBD) or uveitis. Adalimumab can be also considered after failure of etanercept (6-7: 94%). Conclusion: Results from this Delphi study clearly show an overall consensus on the use of adalimumab in the management of PsO and PsA, particularly as first-choice for specific subpopulations (uveitis, IBD, hidradenitis suppurativa). Considering the cost-effectiveness of biosimilars within Italy, adalimumab may represent an effective and safe first-line treatment for patients with moderate-to-severe PsO or PsA, and a valid choice for switching after failure.

Estimation of patients with psoriasis potentially eligible and currently untreated with biological drugs in Italy.

BACKGROUND: Psoriasis (PSO) patients can benefit from the growing availability of novel biological agents, that are often underused or discontinued. This real-world analysis estimated PSO patients potentially eligible and currently untreated with biologics in Italy. METHODS: An observational analysis was performed on administrative databases of a pool of healthcare entities, covering 11.3% of Italian population. During the inclusion period (2010- 2020), patients were identified by: 1) at least one prescription of topical drugs for PSO; or 2) active exemption for PSO; or 3) at least one PSO hospital discharge diagnosis. The index-date was the first PSO identification across inclusion period. Eligibility for biologics was evaluated prior to index-date (characterization period) through two not-mutually exclusive criteria: Criterion A, failure of at least one systemic treatment, and/or Criterion B, onset of psoriatic arthritis (PsA). Data were re-proportioned to the Italian population. RESULTS: The study sample showed a PSO prevalence of 2%. Projection to 2020 national population (N=59,236.213) estimated 1.43 million Italian patients affected by PSO: 95% treated with conventional therapies, 4% with biologics, and 1% untreated. Among those non-treated with biologics, 3.8% of overall PSO patients met one or both eligibility criteria for biologics, specifically 25% met criterion A (failure to conventional treatments), 68% criterion B (PsA co-diagnosis), and 7% met both. About half of them had 1 or 2 comorbidities and 30% above 3. CONCLUSIONS: These findings from real clinical practice estimated about 4% PSO patients potentially eligible for biologics, but still untreated, with nearly one-third exhibiting a complex comorbidity profile.

The Relevant Oral Burden of Patients with Hidradenitis Suppurativa.

INTRODUCTION: Interleukin-17 plays a pivotal role in both hidradenitis suppurativa (HS) and in maintaining oral homeostasis, but their potential link remains unknown. Thus, we aimed to evaluate and quantify the oral burden of patients with HS. METHODS: In this real-life, multicenter, cross-sectional study, patients with HS were clinically evaluated by two board-certified dermatologists and two board-certified dentists. Oral comorbidities were carefully collected with medical history and therapeutic information. RESULTS: A total of 102 patients (44.0 ± 0.9 years, body mass index 27.0 ± 2.2 kg/m2) were enrolled. Remarkably, 48% and 43% did not undergo at least an oral hygiene or a dental visit each year, respectively. Oral disorders were found in 55.9% of patients with HS, in particular 39.2% had caries and 46.7% reported at least one missing tooth. The main oral manifestations in patients with HS were recurrent aphthous stomatitis (N = 19, 19.2%), amalgam tattoo (N = 14, 14.1%), leukoplakia (N = 11, 11.1%), nicotinic stomatitis (N = 9, 9.1%), papilloma (N = 8, 8.1%), and geographic tongue (N = 8, 8.1%). Whilst the main predictor of oral pathological conditions was Hurley staging (P = 0.0276), multivariate regression analysis indicated that gender and International Hidradenitis Suppurativa Severity Score System (IHS4) were the main predictors for the presence of caries and number of missing teeth. CONCLUSION: As a result of the relevant oral burden in patients with HS, dentists should be part of the multidisciplinary team and oral education should be promoted among patients with HS.

Hidradenitis Suppurativa: The Influence of Gender, the Importance of Trigger Factors and the Implications for Patient Habits.

Hidradenitis suppurativa (HS) is a debilitating, chronic, inflammatory skin disease primarily affecting apocrine gland-rich areas of the body. On the one hand, the presence of triggering factors-some identified, others only hypothesized-may initiate or perpetuate the pathogenic process of HS. In addition to cigarette smoking and diet, other trigger factors, including choice of clothing, are frequently observed in clinical practice. On the other hand, the presence of disease may influence habits of HS patients. Indeed, high incidences of sexual and sleep impairment have been reported in these patients. Consequently, alcohol and substance abuse may be a coping strategy for the emotional and psychological disease burden. Furthermore, a greater awareness of gender differences in HS may be important for dermatologists in their own clinical practice (i.e., pregnancy and breastfeeding). Consequently, in this loop interaction, comprehensive knowledge of all factors involved is crucial for the management of HS patients. Thus, the objective of this review is to (i) discuss the influence of gender on HS, (ii) summarize the most frequent triggering factors of HS and (iii) analyze the impact of HS on patient habits.

Therapy of PsO in Special Subsets of Patients.

Psoriasis is a chronic, inflammatory skin disease that may occur at any age, with a bimodal peak of incidence around the age of 16-20 years of age (early onset) and 57-60 years (late-onset). It is estimated that roughly 70% of patients develop the disease before the age of 40, which coincides with the reproductive years. Moreover, psoriasis is a chronic disease, meaning that, with increased life-duration expectancy, the number of patients affected with psoriasis aged over 65 years is going to increase and represent a big therapeutic challenge. Actually, no specific drug recommendation is available, based only on the age of the patients, while therapeutic prescription should take into account that elderly patients have more comorbidities than younger patients, with polypharmacy and an increased risk of drug interactions. Women with psoriasis are more likely to report a worse influence of the disease on their quality of life, and they are more susceptible to the development of depression. Furthermore, pregnancy and lactation represent a major contraindication to several systemic agents, and only a few studies exist providing the safety of certain drugs during these periods of life of a woman, such as certolizumab pegol. In this paper, we discuss systemic therapeutic strategies, including conventional and biological therapies, in a special subset of patients affected with moderate-to-severe psoriasis focusing on elderly patients and on female patients in fertile age, pregnancy, and lactation.

Secukinumab in Patients with Psoriasis and a Personal History of Malignancy: A Multicenter Real-Life Observational Study.

INTRODUCTION: There is limited evidence to guide clinicians on the treatment of psoriasis with biologics in patients with a history of malignancy who are often excluded from clinical trials investigating biologics. The aim of this work is to report a multicenter real-life experience of secukinumab treatment in patients with psoriasis and a personal history of cancer. METHODS: This retrospective observational study included adult patients with moderate-to-severe plaque psoriasis treated with secukinumab for at least 24 weeks and a previous diagnosis of cancer at 15 Italian referral centers. The primary endpoint of the study was tumor recurrence or progression and new cancer diagnosis during treatment. Secondary outcome assessment of secukinumab effectiveness (reduction of Psoriasis Area and Severity Index [PASI] score, improvement of Dermatology Life Quality Index [DLQI], itch and pain). RESULTS: Forty-two patients (27 male) were included. Malignancy was diagnosed in the previous 5 years in 21 (56.8%) and in the previous 10 years in 37 (88.1%). The mean interval between cancer diagnosis and the start of secukinumab treatment was 3.5 ± 3.3 years. No tumor recurrence nor progression occurred over a mean of 56 ± 31.7 weeks of treatment. Three patients developed a new malignancy not related to the previous cancer. At week 48, PASI 90 was reached by 64.7% of patients and PASI 100 by 38.2%. Mean DLQI, itch, and pain VAS scores significantly improved during treatment. CONCLUSIONS: Our multicenter real-life experience is the largest reported to date focusing on a specific biologic and adds evidence to the safety of secukinumab in psoriatic patients with a personal history of cancer.

Successful use of anti-IL-23 molecules in overweight-to-obese psoriatic patients: A multicentric retrospective study.

Advances in treatment with biological agents have changed the course of psoriasis. However observational reports and controlled trials draw attention to the heterogeneity of treatment response and point out that Body Mass index (BMI) may be a key factor for therapy efficacy. Therefore, we investigated the impact of BMI on the efficacy of the most recent biological molecules (anti IL-23 inhibitors) to improve patient care management. A bicentric retrospective study was performed to assess efficacy and safety of guselkumab, risankizumab and tildrakizumab in overweight-to-obese patients with moderate to-severe psoriasis up to 52 weeks of treatment. This study involved 113 patients classified according to BMI as overweight or obese. The clinical response to treatment was assessed by Psoriasis Area and Severity Index (PASI) at week 0, 24 and 52. Across all anti-IL-23 treatments, mean PASI score was ≤2 (1.1) after 6 months of treatment and decreased under 1 after 12 months in all groups. No severe adverse events, death or malignancy cases were recorded. Our results suggest that overweight or obesity does not influence therapeutic response in psoriatic patients treated with anti-IL-23 antagonists. Therefore, therapeutic strategies with this mechanism of action would be more suitable for high BMI patients.

Tuscany consensus for the treatment of moderate-severe psoriasis: update and focus on practical guidelines for place in therapy of anti-IL-17 and anti-IL-23 biologics.

Psoriasis is a common chronic skin disease characterized by a worldwide distribution and a natural tendency towards progression. According to the many clinical forms, the extension of the disease and the many comorbidities, almost the 20% of the patients require a systemic treatment. Biologics have greatly changed the ongoing of psoriasis and the quality of life of psoriasis patients. After the anti-TNF-alpha, which were the first biologics in use for psoriasis, the improvement in knowledge of the pathogenetic mechanisms underlying the disease has led to the development of a series of more specific therapies for psoriasis. This "second generation" of biologics includes the interleukin (IL)-12/23 inhibitor ustekinumab, IL-17 inhibitors (secukinumab and ixekizumab), the IL-17 receptor A (IL-17RA) antagonist brodalumab, and the IL-23 inhibitors guselkumab, risankizumab and tildrakizumab. This study represents an update of the Tuscany consensus focused on the use of new drugs, such as anti-IL-17 and anti-IL-23 in moderate-to-severe psoriasis and their correct place in therapy according to specific clinical requests and in full respect of the current financial restrictions.

Place in therapy of anti-IL-17 and 23 in psoriasis according to the severity of comorbidities: a focus on cardiovascular disease and metabolic syndrome.

INTRODUCTION: Psoriasis is an inflammatory disease nowadays considered not only as a cutaneous but as a systemic disease. Among the numerous comorbidities, psoriatic arthritis (PsA), depression, obesity, and cardiovascular disease (CVD) are considered the most frequent. In addition, metabolic syndrome (MetS), which involves hypertension, dyslipidemia, obesity, and atherosclerosis, has presented a higher prevalence in recent years, especially in psoriatic patients. AREAS COVERED: The mechanism linking anti-tumor necrosis factor (TNF) to MetS and CVD has been widely explained, while there are unknowns about inhibitors of interleukin (IL)-17 and -23. Considering the growing incidence of CVD in the world's population and in particular the strict correlation in patients with psoriasis, it is important to identify therapeutic options able to avoid a negative impact on patients with both conditions. The aim of this paper is to perform a review of the scientific literature with a focus on the pathogenetic mechanism linking psoriasis to CVD and MetS. EXPERT OPINION: The scientific evidence currently available allows us to consider and support the use of anti-IL-17 and anti-IL-23 as a first-line therapy choice in psoriatic patients with high risk of CVDs or MetS.

Italian adaptation of EuroGuiDerm guideline on the systemic treatment of chronic plaque psoriasis.

SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by moderate to severe plaque psoriasis. The content of the guideline includes general information on the scope and purpose, health questions covered, target users and strength/limitations of the guideline, suggestions for disease severity grading and treatment goals. It presents the general treatment recommendations as well as detailed management and monitoring recommendations for the individual drugs including acitretin, cyclosporine, fumarates, methotrexate, adalimumab, apremilast, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, ixekizumab, risankizumab, secukinumab, tildrakizumab and ustekinumab. Moreover, the guideline provides guidance for specific clinical situations such as patient with concomitant psoriatic arthritis, inflammatory bowel disease, a history of malignancies, a history of depression, diabetes, viral hepatitis, disease affecting the heart or the kidneys as well as concomitant neurological disease. Advice on how to screen for tuberculosis and recommendations on how to manage patients with a positive tuberculosis test result are given. It further covers treatment for pregnant women or those with childbearing potential. Information on vaccination, immunogenicity and systemic treatment during the COVID-19 pandemic is also provided.

Long-term safety and efficacy of anti-tumor necrosis factor-alpha biosimilar agents in the treatment of psoriasis: a single center study.

Biosimilar anti-tumor necrosis factor (TNF)-alpha drugs are widely used in the treatment of psoriasis, but only few studies reported the long-term experience of the various biosimilar agents in the real world practice. A monocentric retrospective observational study was performed to assess the long-term efficacy, tolerability, and safety of biosimilars adalimumab (bADA), biosimilar etanercept (bETN), and biosimilar infliximab (bIFX) in psoriasis patients. A total of 73 patients (19 patients treated with bADA, 37 with bETN and 17 with bIFX) were enrolled and observed up to 48 months of follow-up. Regarding the efficacy, across all biosimilar treatments combined, the mean PASI score was ≤2 (1.2) after 12 months of treatments. Notably, the mean PASI score remained relatively stable during all 48 months of follow-up. With regard to tolerability and safety in the present study, 34 (28%) patients experienced adverse events during all biosimilar therapy, and three (4.3%) discontinued treatment. No severe adverse events, death, or malignancy cases were recorded during the study period. Our results support that biosimilar anti-TNF-alpha drugs are effective and well tolerated drugs for the long-term treatment of psoriasis.

Insights into the Pathogenesis of HS and Therapeutical Approaches.

Hidradenitis suppurativa (HS) is a debilitating, chronic, (auto)inflammatory disease primarily affecting apocrine gland-rich areas of the body. Although pathogenic mechanisms responsible for HS have not yet been fully elucidated, it is a multifactorial process whose main target is the terminal follicle. The role of the inflammatory process (and consequently of cytokine milieu) and of several other factors (genetics, lifestyle, hormonal status, microbiome, innate and adaptive immune systems) involved in HS pathogenesis has been investigated (and often defined) over the years with a view to transferring research results from bench to bedside and describing a unique and universally accepted pathogenetic model. This review will update readers on recent advances in our understanding of HS pathogenesis and novel (potential) medical therapies for patients with moderate-to-severe HS.

Characteristic of chronic plaque psoriasis patients treated with biologics in Italy during the COVID-19 Pandemic: Risk analysis from the PSO-BIO-COVID observational study.

Background: The susceptibility of patients with chronic plaque psoriasis and the risks or benefits related to the use of biological therapies for COVID-19 are unknown. Few data about prevalence, clinical course and outcomes of COVID-19 among psoriatic patients were reported. The aims of this study were 1) to assess the prevalence and severity of COVID-19 in psoriatic patients treated with biologic agents during the first phase of the emergency (22 February to 22 April 2020) in Italy, and 2) to report the clinical outcomes of patients who have been exposed to individuals with confirmed SARS-CoV-2 infection. Methods: Patients with moderate-to-severe chronic plaque psoriasis, aged ≥18 years and undergoing treatment with biologic agents as of 22 February 2020, were eligible to be included in PSO-BIO-COVID study. Demographic and clinical characteristics of patients using any biologic for psoriasis treatment between 22 February and 22 April 2020 were registered. Results: A total of 12,807 psoriatic patients were included in the PSO-BIO-COVID study. In this cohort 26 patients (0.2%) had a swab confirmation of SARS-CoV-2 infection. Eleven patients required hospitalization and two died. Conclusion: The incidence of COVID-19 observed in our cohort of psoriatic patients (0.2%) is similar to that seen in the general population (0.31%) in Italy. However, the course of the disease was mild in most patients. Biological therapies may likely lessen 'cytokine storm' of COVID-19, which sometimes lead to multiple organ failure, ARDS, and death.

Management of psoriatic arthritis in rheumatology and dermatology settings: sub-analysis of the Italian population from the international LOOP study.

Psoriatic arthritis (PsA) patients are often treated by dermatology and rheumatology specialities and may receive different treatments. To evaluate the impact of dermatology/rheumatology specialist settings on diagnosis and therapeutic approach in PsA patients. This cross-sectional multicounty study in Italy involved twenty-eight rheumatology or dermatology clinics. Patients with suspected or confirmed PsA were examined by both a dermatologist and a rheumatologist. A total of 413 patients were enrolled and 347 (84%) were diagnosed with PsA. The majority of patients were enrolled from a rheumatology setting (N = 224, 64.6%). Patients with PsA in the dermatology settings had significantly higher disease activity, including skin involvement and musculoskeletal symptoms. Time from PsA onset to diagnosis was 22.3 ± 53.8 vs. 39.4 ± 77.5 months (p = 0.63) in rheumatology and dermatology settings; time from diagnosis to initiation of csDMARD was 7.3 ± 27.5 vs. 19.5 ± 50.6 months, respectively (p < 0.001). In contrast, time from diagnosis to bDMARD use was shorter in dermatology settings (54.9 ± 69 vs. 44.2 ± 65.6 months, p = 0.09, rheumatology vs. dermatology), similar to the time taken from first csDMARDs and bDMARDs (48.7 ± 67.9 vs. 35.3 ± 51.9 months, p = 0.34). The choice to visit a rheumatologist over a dermatologist was positively associated with female gender and swollen joints and negatively associated with delay in time from musculoskeletal symptom onset to PsA diagnosis. This study highlights a diagnostic delay emerging from both settings with significantly different therapeutic approaches. Our data reinforce the importance of implementing efficient strategies to improve early identification of PsA that can benefit from the integrated management of PsA patients. Key Points • A diagnostic delay was observed from both dermatology and rheumatology settings with significantly different therapeutic approaches. • Shared dermatology and rheumatology clinics offer the combined expertise to improve in the early identification and management of PsA.

Anti-tumor necrosis factor agents in psoriasis: addressing key challenges using biosimilars.

INTRODUCTION: Anti-tumor necrosis factor agents are key treatment options in moderate-severe psoriasis. The advent of multiple biosimilars of these drugs provides a major opportunity to address this particular factor by helping to reduce costs. Reduced cost can help improve undertreatment, which is one of the challenges in treating moderate-severe psoriasis. There is now a wealth of real-world evidence demonstrating that patients with psoriasis can be initiated on - or transitioned to - an anti-TNF biosimilar without detrimental effects on overall safety and efficacy. Furthermore, recent results suggest that patients can be switched between different biosimilar versions of the same anti-TNF agent without any compromise in outcomes. AREAS COVERED: In this review, we summarized the role of anti-TNFs in psoriasis, health economic aspects of anti-TNF biosimilars, and their real-world data in clinical practice and registries. EXPERT OPINION: The introduction and competition of anti-TNF biosimilars reduced the cost of biologics and accumulated real-world data support efficacy and safety of anti-TNF biosimilars for psoriasis treatment. Although IL-17 and IL-23 inhibitors show better efficacy in psoriasis patients, long-term efficacy and safety data of anti-TNF and cost-effectiveness of anti-TNF biosimilars may play an important role to increase patient access to biologics through greater adoption of biosimilars.

The psoriatic shift induced by interleukin 17 is promptly reverted by a specific anti-IL-17A agent in a three-dimensional organotypic model of normal human skin culture.

Interleukin 17A (IL-17A), mainly produced by the T helper subclass Th17, plays a key role in the psoriatic plaque formation and progression. The clinical effectiveness of anti-IL-17A agents is documented, but the early and specific mechanisms of their protection are not identified yet. The challenge of the present study is to investigate the possible reversal exerted by a specific anti-IL-17A agent on the psoriatic events induced by IL-17A in a three-dimensional organotypic model of normal human skin. Bioptic skin fragments obtained after aesthetic surgery of healthy women (n=5) were incubated with i) IL-17A biological inhibitor (anti-IL-17A), ii) IL-17A, iii) a combination of IL-17A and its specific IL-17A biological inhibitor (COMBO). A Control group was in parallel cultured and incubation lasted for 24 and 48 h epidermal-side-up at the air-liquid interface. All subjects were represented in all experimental groups at all considered time-points. Keratinocyte proliferation and the presence of epidermal Langerhans cells were quantitatively estimated. In parallel with transmission electron microscopy analysis, immunofluorescence studies for the epidermal distribution of keratin (K)10, K14, K16, K17, filaggrin/occludin, Toll-like Receptor 4, and Nuclear Factor kB were performed. IL-17A inhibited cell proliferation and induced K17 expression, while samples incubated with the anti-IL-17A agent were comparable to controls. In the COMBO group the IL-17A-induced effects were almost completely reverted. Our study, for the first time, elucidates the most specific psoriatic cellular events that can be partially affected or completely reverted by a specific anti-IL-17A agent during the early phases of the plaque onset and progression. On the whole, this work contributes to expand the knowledge of the psoriatic tableau.

Moderate-to-severe psoriasis and pregnancy: impact on fertility, pregnancy outcome and treatment perspectives.

Psoriasis affects 2-4% of the world's population, with no difference between men and women and 70% of patients experiencing disease onset before the age of 40, which coincides with the reproductive years. Few data are available from literature on impact of psoriasis on fertility, course and outcome of pregnancy and risk associated with treatments. Recent studies on other immune-mediated inflammatory diseases, among which psoriasis is also included, indicate that rheumatoid arthritis and inflammatory bowel diseases can impact female fertility and pregnancy outcomes especially during active disease episodes. In psoriasis hormonal and metabolic comorbidities, unhealthy lifestyles and systemic inflammation could also influence the ability to conceive, pregnancy course and birth outcomes. In this article we review current knowledge on reproductive function, course and outcome of pregnancy in women affected by moderate-to-severe psoriasis. Systemic treatments are also considered with a special focus on TNF-alpha blocking agents and implication of molecular structure on placental transportation and fetal exposure.

A multicenter retrospective case-control study on Suspension of TNF-inhibitors and Outcomes in Psoriatic patients (STOP study).

BACKGROUND: There is limited information on patients undergoing withdrawal after long-term treatment with anti-TNF alpha drugs and their clinical evolution during the post-interruption period in real-life settings. The purpose of the present retrospective case-control study was to provide a clearer insight into the clinical management of psoriatic patients with adequate response to long-term adalimumab, etanercept and infliximab treatment once these biologic agents are interrupted. METHODS: A total of 270 patients undergoing anti-TNF alpha agents discontinuation and 253 controls treated with a continuous regimen were enrolled. The primary endpoint was the change in disease activity in each study group over six months (or until treatment of psoriatic recurrence) as measured by the PASI score every month. Then, we evaluated the rate of and time to relapse, the rate of clinical worsening (PASI≥5) and the clinical variables influencing the loss of response. RESULTS: Our study showed that about 50% of patients achieving a long-term and optimal response to the aforementioned anti-TNF alpha agents did not experience any relapse over a 6-month follow-up period after withdrawal. We also observed that subjects displaying a complete remission (PASI=0) at anti-TNF alpha therapy withdrawal experienced less frequently disease worsening and/or relapse compared to subjects having a PASI>0. CONCLUSIONS: Our findings confirmed that all three anti-TNF alpha agents tend to retain their effectiveness upon re-administration in case of recurrence, even if they have been previously used for long time.