Efficacy and safety of fixed-dose combination calcipotriol/betamethasone dipropionate foam for the treatment of psoriasis.

The fixed-dose combination calcipotriol (Cal; 50 µg/g) plus betamethasone dipropionate (BD; 0.5 mg/g) ointment and gel formulations have well-established efficacy profiles in the treatment of psoriasis vulgaris (chronic plaque psoriasis); this combination has been shown to produce favourable outcomes versus either monotherapy. To improve upon the efficacy and cosmetic acceptability of these treatments Cal/BD foam was developed, demonstrating superior efficacy in Phase II/III studies compared with either of its monocomponents, Cal/BD ointment, Cal/BD gel and various other therapies for the treatment of psoriasis. Multiple outcome measures were evaluated in the clinical studies, including physician's global assessment of disease severity and modified psoriasis area and severity index. Of note, 38-55% of patients across studies achieved a physician's global assessment of 'clear' or 'almost clear' after 4 weeks of Cal/BD treatment. This superior efficacy was not associated with an increased frequency or severity of adverse events, and there was no evidence for dysregulation of the hypothalamic-pituitary-adrenal axis or calcium homeostasis. Overall, Cal/BD foam was efficacious, with a good tolerability profile consistent with established Cal/BD formulations.

Co-infection of SARS-CoV-2 with Chlamydia or Mycoplasma pneumoniae: a case series and review of the literature.

INTRODUCTION: The novel coronavirus SARS-CoV-2 has spread all over the world causing a global pandemic and representing a great medical challenge. Nowadays, there is limited knowledge on the rate of co-infections with other respiratory pathogens, with viral co-infection being the most representative agents. Co-infection with Mycoplasma pneumoniae has been described both in adults and pediatrics whereas only two cases of Chlamydia pneumoniae have been reported in a large US study so far. METHODS: In the present report, we describe a series of seven patients where co-infection with C. pneumoniae (n = 5) or M. pneumoniae (n = 2) and SARS-CoV-2 was detected in a large teaching hospital in Rome. RESULTS AND CONCLUSION: An extensive review of the updated literature regarding the co-infection between SARS-CoV-2 and these atypical pathogens is also performed.

Patient perceptions of clear/almost clear skin in moderate-to-severe plaque psoriasis: results of the Clear About Psoriasis worldwide survey.

BACKGROUND: Therapeutic advances have made the achievement of clear/almost clear skin possible for many patients with moderate-to-severe plaque psoriasis. OBJECTIVE: To determine patient perceptions of the impact of psoriasis and of attaining clear/almost clear skin. METHODS: Global survey of patients with moderate-to-severe psoriasis. RESULTS: A total of 8338 patients from 31 countries participated. The majority (57%) had not achieved self-assessed clear/almost clear skin with their current therapy, and 56% of those who had not met this goal believed it would be impossible to do so. Among the patients who had clear/almost clear skin, 73% had not initiated their current treatment until >1 year after psoriasis diagnosis, and 28% had to wait >5 years. Eighty-four percent of all respondents experienced discrimination and/or humiliation due to psoriasis, and many reported negative effects on work, intimate relationships, sleep and mental health. Patients without clear/almost clear skin reported that such achievement would open new possibilities, such as swimming (58%), a wider choice of clothing (40%), and meeting new people (26%). A limitation of this study, as with any survey-based research, is that selection and recall bias may have been present. Additionally, respondent definitions of clear/almost clear skin were subjective and may have varied. CONCLUSION: Despite the importance of clear/almost clear skin to psoriasis patients, most are still not achieving it, and many are unaware it is possible.

Patient-dermatologist agreement in psoriasis severity, symptoms and satisfaction: results from a real-world multinational survey.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory disease, which often requires lifelong treatment. A strong partnership between the patient and healthcare practitioners should help to achieve effective treatment outcomes. OBJECTIVE: To assess concordance of views between patients with psoriasis and their treating dermatologists relative to psoriasis severity, presence of symptoms and satisfaction with disease control achieved. METHODS: We used data from the Growth from Knowledge (GfK) Disease Atlas real-world evidence program, a syndicated, retrospective, cross-sectional survey among dermatologists and their systemic therapy eligible patients with psoriasis, conducted across nine countries. Concordance was measured through patients and their dermatologist's identical answers to the same survey questions. Concordance was evaluated using percentage agreement between dermatologists and their patients, and Cohen's kappa (κ) statistic. The level of concordance was defined as 'none' (κ ≤ 0), 'none to slight' (0.01-0.20), 'fair' (0.21-0.40), 'moderate' (0.41-0.60), 'substantial' (0.61-0.80) and 'almost perfect' (>0.8). The analysis was conducted for the overall population and for each participating country. RESULTS: Overall, 524 dermatologists and 3821 patients with psoriasis were included in the survey. Concordance of patient and dermatologist perceptions of psoriasis severity was fair both at diagnosis, and at the time of the survey (61% agreement, κ = 0.326 and 55% agreement, κ = 0.370, respectively). Higher levels of concordance were reported when patients assessed their psoriasis as moderate-to-severe (using Investigator's Global Assessment/Physician's Global Assessment [IGA/PGA] 5-point scale of 3 or 4). Concordance regarding symptoms ranged from fair to moderate (κ = 0.241-0.575). Satisfaction with psoriasis control was fair (39% agreement, κ = 0.213). Results showed different patterns of concordance across the participating countries although a low concordance was observed on the satisfaction with psoriasis control in all of them. CONCLUSION: Results from this multinational real-world survey indicate different perceptions between patients with psoriasis and their dermatologist with respect to psoriasis severity, symptoms and disease control.

A multidimensional assessment of the burden of psoriasis: results from a multinational dermatologist and patient survey.

BACKGROUND: Psoriasis is a chronic, immune-mediated disease, characterized by symptoms that include itching and skin pain and is often associated with comorbidities. Patients have a substantial detriment to quality of life (QoL) and work productivity with associated cost burden. OBJECTIVES: To investigate the incremental burden of comorbidities, itch and affected body areas among systemic eligible patients with psoriasis, using a multinational survey of dermatologists and their patients with psoriasis. METHODS: Multinational data from the Growth from Knowledge (GfK) Disease Atlas Global Real-World Evidence program were used. Eligible patients were identified as those who were currently having or had ever had moderate-to-severe psoriasis, and must have been receiving prescription treatments at the time of the survey. Multivariable regression analyses were conducted to assess the incremental burden among psoriasis patients with physical and psychological comorbidities, itch and affected visible and sensitive body areas vs. psoriasis patients without these conditions, respectively. RESULTS: The study enrolled 3821 patients with psoriasis, from nine countries, with an average Psoriasis Area and Severity Index score of 6·4. The presence of comorbidities was associated with a significant increase in the likelihood of skin pain, lower QoL, greater work impairment and increased usage of medical resources (except in psoriasis patients with obesity and type 2 diabetes). Psoriasis patients suffering from itch and those with visible and sensitive affected body areas also had impaired QoL vs. those without these conditions. CONCLUSIONS: Psoriasis patients with physical and psychological comorbidities, itch and affected visible and sensitive body areas had lower QoL and greater work impairment compared to those without these conditions.

Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis: Subgroup analysis of Latin American patients in the phase 3 randomized UNCOVER-3 study / Comparación de ixekizumab y etanercept o placebo en la psoriasis de moderada a grave: análisis del subgrupo de pacientes latinoamericanos de la fase 3 del estudio aleatorizado UNCOVER-3

Background and objectives: Ixekizumab demonstrated greater efficacy than placebo and etanercept in UNCOVER-3. Subgroup analysis of Latin American patients was performed. We report 12-week and 60-week data. Patients and methods: Analysis included 102 Latin American patients randomized to receive placebo (n = 14), etanercept 50 mg twice weekly (n=30), or ixekizumab 160-mg starting dose followed by 80 mg every 2 weeks (Q2W; n = 29) or every 4 weeks (Q4W; n = 29). At week 12, patients maintaining efficacy response and adequate overall safety were assigned, at the discretion of the investigator, to long-term extension with ixekizumab Q4W. Results: At week 12, Psoriasis Area and Severity Index (PASI) 100 scores were 0%, 20.0% (p = 0.075 vs placebo), 62.1% (p < 0.001 vs placebo; p = 0.001 vs etanercept), and 48.3% (p = 0.002 vs placebo; p = 0.023 vs etanercept) for placebo, etanercept, ixekizumab Q2W, and ixekizumab Q4W, respectively. Among patients who continued therapy up to week 60 (n = 97), PASI 100 scores were 71.4%, 60.0%, 77.8%, and 57.7% for patients who received induction placebo, etanercept, ixekizumab Q2W, and ixekizumab Q4W, respectively (non-responder imputation). By week 60, ≥1 serious adverse event was experienced by 7.1% (n = 1/14), 3.3% (n = 1/30), 14.8% (n = 4/27), and 0% (n = 0/26) of patients who received induction placebo, etanercept, ixekizumab Q2W, and ixekizumab Q4W, respectively. There were no cases of active tuberculosis with ixekizumab treatment through 60 weeks. Conclusions: In Latin American patients, both ixekizumab dosing regimens demonstrated greater efficacy than etanercept for treating psoriasis over 12 weeks. The safety profile of ixekizumab through 60 weeks was well tolerated and consistent with the overall profile (AU)

Antecedentes y objetivos: Ixekizumab demostró una mayor eficacia que el placebo y etanercept en el estudio UNCOVER-3. Tras realizar un análisis del subgrupo de pacientes latinoamericanos, se presentan los resultados transcurridas 12 y 60 semanas. Pacientes y métodos: El análisis incluyó a 102 pacientes latinoamericanos aleatorizados para la administración de placebo (n=14), etanercept 50 mg 2 veces por semana (n = 30), o ixekizumab 160mg como dosis inicial y 80mg cada 2 semanas (Q2W; n=29) o 4 semanas (Q4W; n = 29). A la semana 12 los pacientes con buena respuesta de eficacia y ausencia de efectos adversos fueron asignados al tratamiento de ampliación a largo plazo con ixekizumab Q4W, a discreción del investigador. Resultados: A las 12 semanas las puntuaciones del PASI fueron del 0%, 20% (p = 0,075 vs placebo), 62,1% (p < 0,001 vs placebo; p = 0,001 vs etanercept) y 48,3% (p = 0,002 vs placebo; p = 0,023 vs etanercept) para placebo, etanercept, ixekizumab Q2W, e ixekizumab Q4W, respectivamente. Entre los pacientes que prosiguieron la terapia hasta la semana 60 (n = 97) las puntuaciones PASI 100 fueron del 71,4%, 60%, 77,8%, y 57,7% para los pacientes a quienes se administró placebo de inducción, etanercept, ixekizumab Q2W e ixekizumab Q4W, respectivamente (imputación del no respondedor). En la semana 60 ≥1 presentaron reacción adversa grave el 7,1% (n = 1/14), 3,3% (n = 1/30), 14,8% (n = 4/27) y 0% (n = 0/26) de los pacientes a quienes se administró placebo, etanercept, ixekizumab Q2W e ixekizumab Q4W, respectivamente. No se produjeron casos de tuberculosis activa con el tratamiento de ixekizumab a lo largo de las 60 semanas. Conclusiones: En los pacientes latinoamericanos ambos regímenes de dosificación de ixekizumab demostraron mayor eficacia que etanercept para el tratamiento de la psoriasis durante 12 semanas. En cuanto al perfil de seguridad, ixekizumab a lo largo de 60 semanas fue bien tolerado y consistente con el perfil general (AU)

Biosimilars for psoriasis: worldwide overview of regulatory guidelines, uptake and implications for dermatology clinical practice.

The introduction of biological drugs for the treatment of patients with psoriasis has revolutionized treatment paradigms and enabled numerous patients to achieve disease control with an acceptable safety profile. However, the high cost of biologics limits access to these medications for the majority of patients worldwide. In recent years, the introduction of biosimilars for inflammatory diseases has become a fast evolving field. The future use of biosimilars offers the potential for decreased cost and increased access to biologics for patients with psoriasis. For approval of biosimilars, different regulatory agencies use highly variable methods for definition, production, approval, marketing and postmarketing surveillance. Due to potential interchangeability between biologics and biosimilars, traceability and pharmacovigilance are required to collect accurate data about adverse events in patients with psoriasis; spontaneous reporting, registries and use of 'big data' should facilitate this process on a global basis. The current article describes biosimilar regulatory guidelines and examples of biosimilar uptake in clinical practice in several countries around the world. As it is apparent that biological therapy treatment decisions may become more physician independent, the International Psoriasis Council recommends that dermatologists should take an active role in the development of biosimilar prescribing policies with their respective healthcare settings and government agencies.

Infections from seven clinical trials of ixekizumab, an anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriasis.

BACKGROUND: Infections are associated with biological therapies in psoriasis. OBJECTIVES: To summarize the incidence of infections in patients with moderate-to-severe psoriasis treated with ixekizumab, an anti-interleukin-17A monoclonal antibody. METHODS: Infections are summarized from an integrated database of seven controlled and uncontrolled ixekizumab psoriasis trials. Data are presented from placebo-controlled induction (weeks 0-12; UNCOVER-1, UNCOVER-2 and UNCOVER-3) and maintenance periods (weeks 12-60; UNCOVER-1 and UNCOVER-2), and all patients exposed to ixekizumab pooled from all seven trials. Comparisons with etanercept were made during the induction period of two trials (UNCOVER-2 and UNCOVER-3). Incidence and exposure-adjusted incidence rates (IRs) per 100 patient-years (PYs) are reported. RESULTS: Overall, 4209 patients were treated with ixekizumab (6480 PY). During induction (weeks 0-12), overall infection rates were higher in patients treated with ixekizumab (27%) vs. placebo (23%, P < 0·05); however, specific infection rates were comparable overall across treatment groups. IRs of infections did not increase with longer-term exposure. For all patients treated with ixekizumab (all seven trials), the incidence of serious infections was low (2%, IR 1·3). Candida infections, including eight cases of oesophageal candidiasis, were adequately managed with antifungal therapy, were noninvasive and did not lead to discontinuation. CONCLUSIONS: Overall, infections occurred in a higher percentage of patients treated with ixekizumab vs. placebo during the first 12 weeks of treatment; however, specific infection rates were comparable overall across treatment groups. Incidences of serious infections were low and similar across treatment groups.

Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis: Subgroup analysis of Latin American patients in the phase 3 randomized UNCOVER-3 study.

BACKGROUND AND OBJECTIVES: Ixekizumab demonstrated greater efficacy than placebo and etanercept in UNCOVER-3. Subgroup analysis of Latin American patients was performed. We report 12-week and 60-week data. PATIENTS AND METHODS: Analysis included 102 Latin American patients randomized to receive placebo (n=14), etanercept 50mg twice weekly (n=30), or ixekizumab 160-mg starting dose followed by 80mg every 2 weeks (Q2W; n=29) or every 4 weeks (Q4W; n=29). At week 12, patients maintaining efficacy response and adequate overall safety were assigned, at the discretion of the investigator, to long-term extension with ixekizumab Q4W. RESULTS: At week 12, Psoriasis Area and Severity Index (PASI) 100 scores were 0%, 20.0% (p=0.075 vs placebo), 62.1% (p<0.001 vs placebo; p=0.001 vs etanercept), and 48.3% (p=0.002 vs placebo; p=0.023 vs etanercept) for placebo, etanercept, ixekizumab Q2W, and ixekizumab Q4W, respectively. Among patients who continued therapy up to week 60 (n=97), PASI 100 scores were 71.4%, 60.0%, 77.8%, and 57.7% for patients who received induction placebo, etanercept, ixekizumab Q2W, and ixekizumab Q4W, respectively (non-responder imputation). By week 60, ≥1 serious adverse event was experienced by 7.1% (n=1/14), 3.3% (n=1/30), 14.8% (n=4/27), and 0% (n=0/26) of patients who received induction placebo, etanercept, ixekizumab Q2W, and ixekizumab Q4W, respectively. There were no cases of active tuberculosis with ixekizumab treatment through 60 weeks. CONCLUSIONS: In Latin American patients, both ixekizumab dosing regimens demonstrated greater efficacy than etanercept for treating psoriasis over 12 weeks. The safety profile of ixekizumab through 60 weeks was well tolerated and consistent with the overall profile.

Biosimilars for psoriasis: clinical studies to determine similarity.

Biosimilars are drugs that are similar, but not identical, to originator biologics. Preclinical analytical studies are required to show similarity on a molecular and structural level, but efficacy and safety studies in humans are essential to determining biosimilarity. In this review, written by members of the International Psoriasis Council, we discuss how biosimilars are evaluated in a clinical setting, with emphasis on extrapolation of indication, interchangeability and optimal clinical trial design.