Effectiveness and safety of liposomal rapamycin for the treatment of facial angiofibromas in tuberous sclerosis.

AIM: Topical rapamycin is the pharmacological treatment of choice for facial angiofibromas in rare tuberous sclerosis disease. A new, more advanced, and complex formula was developed in our pharmacy service: rapamycin 0.4% liposomal formulation, with better organoleptic characteristics and a more favorable release profile of the active ingredient. The purpose of this study is to evaluate the effectiveness and safety of liposomal topical rapamycin for the treatment of facial injuries in this rare disease. METHOD: This was an observational, prospective, and multicenter study. Effectiveness was evaluated mainly through facial angiofibromas severity index (FASI), investigator's global assessment (IGA) scores, and dermatology life quality index (DLQI) questionnaire. To assess the safety profile of rapamycin, adverse reactions were reported, and blood tests and blood rapamycin levels were performed during treatment. RESULTS: Eleven patients were included, of which 8/11 (73%) patients obtained successful treatment according to FASI and IGA scores after 24 weeks of treatment. Statistical analysis demonstrated a significant improvement (p<.05) in FASI and IGA scores, erythema, and FA size after treatment with rapamycin liposomal formulation (FASI before treatment, median (interquartile range): 6.0 (2.0), FASI after treatment: 3.5 (2.0), p=.0063). Five patients also improved their quality of life after treatment. Regarding safety profile of rapamycin, the most common adverse reaction was mild pruritus and 2 patients reported erythema, who discontinued treatment prematurely. All hematological tests were normal, and blood rapamycin levels were undetectable. CONCLUSIONS: After galenic improvements and clinical evaluations, the rapamycin liposomal formulation proved to be effective and safe for this therapeutic indication. This new formulation was included as a magistral formula in our hospital pharmacy service, now accessible for prescribing by dermatologists. Drug development in hospital pharmacy is often the only pharmacological alternative available to treat the symptoms of rare diseases, when treatment options are limited or inadequate.

Efficacy of Omalizumab for the treatment of Bullous Pemphigoid. Spanish multicenter real-world experience.

BACKGROUND: Bullous Pemphigoid (BP) is the most common autoimmune blistering disease. Most patients are elderly and associate multiple comorbidities. Topical and systemic corticosteroids are considered as the first-line treatment for BP and immunosuppressors are used as steroid-sparing treatments but both have side effects and contraindications which are even more common in this elderly population. New treatments targeting interleukins and receptors related to BP pathogenesis have been proposed to decrease this side effects while achieving equal or better effectiveness response rates.Omalizumab is a monoclonal antibody that targets IgE that has been proposed for the treatment of BP due to the evidence that IgE autoantibodies play an essential role in BP pathogenesis. OBJECTIVES AND METHODOLOGY: To assess the efficacy and security of Omalizumab for the treatment of BP, we carried out a multicenter, retrospective, observational study including patients diagnosed of BP who received omalizumab for at least 3 months from 15 tertiary hospitals in Spain. IgE levels prior to treatment was measured and we evaluate the possible correlation with clinical response. We excluded patients treated with Omalizumab for less than 3 months as we consider this duration is insufficient for a comprehensive assessment of its efficacy. To evaluate the effectiveness of the treatment we used the percentage of BSA improvement. RESULTS: We included 36 patients. The vast majority associate multiple comorbidities and all patients had used other systemic therapies apart from corticoids before Omalizumab.83% experienced some kind of treatment response and 42% of all patient treated achieved complete response.We did not find any correlation between higher levels and a better response (p=0,1791).All patients tolerated Omalizumab without reported side-effects. CONCLUSIONS: Omalizumab is a good therapeutic alternative for BP as it obtained clinical response in most patients and nearly half of the cases achieving complete response. It showed no side effects which is crucial in elderly patients suffering from BP.

Psoriasis dermatitis, a common phenotype of early forms of both psoriasis and atopic dermatitis in children: A prospective multicenter study.

BACKGROUND: Psoriasis (Ps) and atopic dermatitis (AD) are chronic systemic immune-mediated diseases that can coexist in an overlapping condition called psoriasis dermatitis (PD). PD patients have intermediate lesions with characteristics of both Ps and AD. PD is very rare in adults but much more frequent in children. Little is known, however, about the course of PD in the pediatric population. The aim of this study was to evaluate the percentage of PD cases in children that evolved to a definite form of Ps or AD and to identify any clinical or epidemiological variables that could predict the course of the disease. METHODS: We performed a prospective multicenter cohort study of children diagnosed with PD between January 2018 and December 2020. We collected participants' clinical and epidemiological characteristics, and pediatric dermatologists determined the percentage of participants who developed Ps or AD. RESULTS: The study included 24 children with PD, with a median age of 7.0 years. After a median follow-up period of 31 months, 83.3% of cases had evolved to a definite form of Ps or AD (44.4% to Ps and 38.9% to AD). Younger age and family history of Ps were associated with progression to AD. Participants who progressed to AD or Ps had a longer follow-up than those with an unchanged PD diagnosis. CONCLUSIONS: Given sufficient time, a large percentage of PD cases in children will evolve into Ps or AD. Long-term clinical follow-up is necessary for a correct diagnosis.

Upadacitinib effectiveness in moderate-to-severe atopic dermatitis: A real-life multicentre and retrospective study.

This was an observational and retrospective multicentre study conducted on adolescents and adults diagnosed with moderate-to-severe atopic dermatitis (AD) and treated with upadacitinib. Disease severity was measured by Eczema Area and Severity Index (EASI), validated investigator global assessment for AD and pruritus Numerical Rating Scale (NRS) at baseline and Weeks 4, 16, 24 and 52 (when available). Twenty-one patients were included. All patients had previously received topical and systemic corticosteroids. Rapid response to upadacitinib was observed: Mean (SD) EASI score was 19.8 (6.5) at baseline, and 3.1 (4.2), 0.9 (1.4), 0.6 (0.6) and 0.6 (0.6) at the Weeks 4, 16, 24 and 52, respectively. Itch was controlled at Week 4 in all patients (mean [SD] NRS score 7.6 [1.9] baseline, 1.5 [1.3] W4). Severe infections or major adverse cardiovascular events were not reported. We highlight effectiveness and rapid response of upadacitinib in achieving itch control even in long-standing recalcitrant cases.

Effectiveness and safety of tildrakizumab for the treatment of psoriasis in real-world settings at 24 weeks: A retrospective, observational, multicentre study by the Spanish Psoriasis Group.

BACKGROUND: Tildrakizumab is a humanized, IgG1/κ antibody that interacts with the p19 subunit of interleukin 23. It is approved for the treatment of moderate-to-severe plaque psoriasis. Real-world evidence on the effectiveness and safety of tildrakizumab is limited. OBJECTIVES: To assess the effectiveness and safety of tildrakizumab at 24 weeks in patients with moderate-to-severe plaque psoriasis in routine clinical practice. METHODS: Retrospective, observational, multicentre study including adult patients with moderate-to-severe plaque psoriasis treated with tildrakizumab under real-life conditions. Patient data were extracted from anonymized electronic medical records. Statistical analysis was performed using SPSS22. RESULTS: A total of 190 patients were included. About 53.9% were men with a mean age of 51.45 (SD 3.9) and a mean BMI of 29.13 (SD 6.21). About 79.8% (132 out of 190) of patients had previously received biological therapy (BT) and 17.3% (33 out of 191) had psoriatic arthritis. Baseline PASI was 10.7 (SD 6.53). Up to 109 patients reached Week 24 and at this point mean baseline PASI decreased to 1.7 (SD 4.8), representing an 88.79% mean PASI reduction. At 6 months, 87.1% and 40.3% of the treated patients achieved PASI ≤3 and ≤1, respectively. At Week 24 mean BSA decreased from 13.2 (SD 10.07) to 1.6 (SD 4.40) and mean DLQI went from 12.5 (SD 7.12) to 1.2 (SD 3.27). Multivariate analysis showed no differences when effectiveness was correlated with gender, obesity, psoriatic arthritis or prior exposure to BT. The rate of adverse events (AE) was 5.9% (11 out of 190), where infections were the most frequent AE (4 out of 11). One patient suffered a haemorrhagic ictus and one patient died due to causes unrelated to the study. CONCLUSION: Tildrakizumab was effective and safe in a large cohort of patients with moderate-to-severe plaque psoriasis treated in a routine clinical setting.

Clinicopathological characteristics of cutaneous and mucocutaneous leishmaniasis in patients treated with TNF-α inhibitors.

BACKGROUND AND OBJECTIVES: The increasing use of biologics in the treatment of inflammatory diseases has led to more cases of leishmaniasis in patients subjected to iatrogenic immunosuppression. The main objective was to describe the characteristics of the patients with cutaneous (CL) or mucocutaneous (MCL) leishmaniasis who were receiving a biological therapy at the time of diagnosis. PATIENTS AND METHODS: A multicenter retrospective study was design based on a cohort of patients diagnosed with CL or MCL. All patients who were being treated with biologicals were included. For each case, two matched non-exposed patients were included for comparison. RESULTS: 38 patients were diagnosed with CL or MCL while being treated with tumor necrosis factor alpha (TNF-α) inhibitors. Leishmaniasis presented more frequently as a plaque (58.3%) with a larger median lesion size (2.5 cm), ulceration (92.1%), and required a greater median number of intralesional meglumine antimoniate infiltrations (3 doses) (P < 0.05) than in non-exposed patients. We found no systemic involvement in patients being treated with anti-TNF-α. We did not find differences regarding the treatment characteristics whether biologic therapy was modified or not. CONCLUSIONS: Although management should be individualized, maintenance of biologic therapy does not seem to interfere with treatment of CL or MCL.

Criteria used to define tumor necrosis factor-alpha inhibitors failure in patients with moderate-to-severe psoriasis: a systematic literature review.

BACKGROUND: Determining tumor necrosis factor-alpha inhibitors (anti-TNF-α) failure is still a challenge in the management of moderate-to-severe psoriasis. Thus, our comprehensive systematic literature review aimed to gather information on the criteria used to define anti-TNF-α failure. We also aimed to discover the main reasons for anti-TNF-α failure and define subsequently administered treatments. MATERIALS AND METHODS: We conducted a systematic review following review and reporting guidelines (Cochrane and PRISMA). International (Medline/PubMed and Cochrane Library) and Spanish databases (MEDES, IBECS), and gray literature were consulted to identify publications issued until April 2021 in English or Spanish. RESULTS: Our search yielded 58 publications. Of these, 37 (63.8%) described the criteria used to define anti-TNF-α primary or secondary failure. Criteria varied across studies, although around 60% considered Psoriasis Area and Severity Index (PASI)-50 criteria. Nineteen (32.8%) reported the reasons for treatment failure, including the lack or loss of efficacy and safety-related problems, mainly infections. Finally, 29 (50%) publications outlined the treatments administered after anti-TNF-α: 62.5% reported a switch to another anti-TNF-α and 37.5% to interleukin (IL)-inhibitors.Our findings suggest a need to standardize the management of anti-TNF-α failure and reflect the incorporation of new targets, such as IL-inhibitors, in the treatment sequence.KEY MESSAGESIn the treatment of psoriasis, the primary and secondary anti-TNF-α failure criteria differ widely in the scientific literature.The strictest efficacy criteria for defining anti-TNF-α failure, or those recommended by guidelines such as PASI75, were underused both in clinical trials and observational studies.Most studies failed to consider patient-reported outcomes in assessing psoriasis treatment efficacy, which contrasts with recent recommendations on the inclusion of patient-reported HRQoL as a supporting criterion when considering clinical outcomes.

Guselkumab effectiveness, and posology in patients with moderate to severe hidradenitis suppurativa: A retrospective bicentric experience.

Hidradenitis suppurativa (HS) is a chronic, inflammatory, and recalcitrant skin disease of the terminal hair follicle. Therapeutic alternatives in HS are limited nowadays. Adalimumab, is the only approved biological treatment for patients with moderate to severe HS, and some patients do not reach an optimal response, or experience a progressive response loss, needing therapeutic alternatives. IL-23 pathway is also involved in HS pathogenesis, so its blockade could contribute to reach disease control. Guselkumab is a monoclonal antibody targeting the p19 subunit of extracellular IL-23, currently approved for psoriasis in adults, and recently some authors have reported its effectiveness in patients with moderate to severe HS refractory to other systemic treatments, becoming a hope for some patients. However adequate dosing and intervals have not been determined yet, so in most published series, doses approved for psoriasis are commonly used. On this topic a retrospective bicentric study including HS patients treated with guselkumab in the dermatologic departments of university hospitals Puerta de Hierro of Majadahonda (Madrid, Spain) and Doctor Peset of Valencia (Valencia, Spain) was conducted. We reported effectiveness, dosage and frequency of administration in the cohort, in order to establish the most effective dosage regimen and to clarify the potential role of guselkumab for this disease.

Impact of Pharmacokinetic and Pharmacodynamic Properties of Monoclonal Antibodies in the Management of Psoriasis.

The treatment of psoriasis has been revolutionized by the emergence of biological therapies. Monoclonal antibodies (mAb) generally have complex pharmacokinetic (PK) properties with nonlinear distribution and elimination. In recent years, several population pharmacokinetic/pharmacodynamic (PK/PD) models capable of describing different types of mAb have been published. This study aims to summarize the findings of a literature search about population PK/PD modeling and therapeutic drug monitoring (TDM) of mAb in psoriasis. A total of 22 articles corresponding to population PK/PD models of tumor necrosis factor (TNF)-α inhibitors (adalimumab and golimumab), interleukin (IL)-23 inhibitors (guselkumab, tildrakizumab, and risankizumab), IL-23/IL-12 inhibitor (ustekinumab), and IL-17 inhibitors (secukinumab, ixekizumab, and brodalumab) were collected. A summary of the clinical trials conducted so far in psoriasis was included, together with the current structural population PK and PD models. The most significant and clinical covariates were body weight (BW) and the presence of immunogenicity on clearance (CL). The lack of consensus on PK/PD relationships has prevented establishing an adequate dosage and, therefore, accentuates the need for TDM in psoriasis.

Psoriasis induced by biological therapy.

OBJECTIVE: To describe a multicentre case series of new onset or worsening of psoriasis in patients treated with biological drugs. MATERIAL AND METHODS: Descriptive study. We reviewed the clinical history of patients with chronic inflammatory disease (CID) treated with biological drugs, who developed new onset or worsening of psoriasis during the follow-up period. RESULTS: Twenty-six cases of paradoxical psoriasis (PP) were recorded. Ninety-three percent of the patients were treated with anti-TNFα and adalimumab was responsible for 50% of the cases. Only 5 patients had a personal history of psoriasis. The biological drug was discontinued in 13 patients. Lesion recurrence was more frequent when another anti-TNFα was reintroduced. CONCLUSIONS: The PP is a reversible adverse effect that can be observed in patients exposed to biological drugs, mainly anti-TNFα.