Mona Malakouti

Biologic fatigue in psoriasis

Background: Over the past 15 years, biologic medications have greatly advanced psoriasis therapy. However, these medications may lose their efficacy after long-term use, a concept known as biologic fatigue. We sought to review the available data on biologic fatigue in psoriasis and identify strategies to help clinicians optimally manage patients on biologic medications in order to minimize biologic fatigue. Methods: We reviewed phase III clinical trials for the biologic medications used to treat psoriasis and performed a PubMed search for the literature that assessed the loss of response to biologic therapy. Results: In phase III clinical trials of biologic therapies for the treatment of psoriasis, 20–32% of patients lost their PASI-75 response during 0.8–3.9 years of follow-up. A study using infliximab reported the highest percentage of patients who lost their response (32%) over the shortest time-period (0.8 years). Although not consistently reported across all studies, the presence of antidrug antibodies was associated with the loss of response to treatment with infliximab and adalimumab. Conclusion: Biologic fatigue may be most frequent in those patients using infliximab. Further studies are needed to identify risk factors associated with biologic fatigue and to develop meaningful antidrug antibody assays.

Anti-IL-17 phase II data for psoriasis: A review.

UNLABELLED Abstract Background: Studies investigating the molecular basis of psoriasis have established the central roles of TNFα, interleukin (IL)-12, IL-22 and IL-23 and there is increasing evidence that IL-17 plays a critical role in the complex pathophysiology. Preclinical studies suggest that IL-17 is a desirable therapeutic target for psoriasis treatment. METHODS We reviewed the results of the phase II clinical trials for the anti-IL-17 agents secukinumab, ixekizumab and brodalumab in order to assess the efficacy and safety profile of each agent. RESULTS By week 12, the proportion of patients reaching Psoriasis Area and Severity Index (PASI 75) was comparable among the most efficacious dosage between the different agents (secukinumab 82%, ixekizumab 83% and brodalumab 82%; p<0.001 compared to placebo for all agents). The safety profiles of the agents were similar with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections and injection site reaction. A small percentage of patients experienced low-grade neutropenia that was predominantly transient and asymptomatic. CONCLUSION The anti-IL-17 agents demonstrated a rapid and robust clinical improvement accompanied by a favorable short-term safety profile. The results of the phase II trials support the theory that the IL-17 pathway is an essential target in psoriasis treatment.Abstract Background: Studies investigating the molecular basis of psoriasis have established the central roles of TNFα, interleukin (IL)-12, IL-22 and IL-23 and there is increasing evidence that IL-17 plays a critical role in the complex pathophysiology. Preclinical studies suggest that IL-17 is a desirable therapeutic target for psoriasis treatment. Methods: We reviewed the results of the phase II clinical trials for the anti-IL-17 agents secukinumab, ixekizumab and brodalumab in order to assess the efficacy and safety profile of each agent. Results: By week 12, the proportion of patients reaching Psoriasis Area and Severity Index (PASI 75) was comparable among the most efficacious dosage between the different agents (secukinumab 82%, ixekizumab 83% and brodalumab 82%; p < 0.001 compared to placebo for all agents). The safety profiles of the agents were similar with the most frequently reported adverse events of nasopharyngitis, upper respiratory infections and injection site reaction. A small percentage of patients experienced low-grade neutropenia that was predominantly transient and asymptomatic. Conclusion: The anti-IL-17 agents demonstrated a rapid and robust clinical improvement accompanied by a favorable short-term safety profile. The results of the phase II trials support the theory that the IL-17 pathway is an essential target in psoriasis treatment.

The role of IL-17 in psoriasis

Abstract Background: Psoriasis is a chronic skin condition traditionally believed to involve the Th1 pathway. Recently, the IL-23/Th17/IL-17 pathway has been highlighted in the pathogenesis of psoriasis and other autoimmune inflammatory conditions. From a clinician’s perspective, we sought to review the basic science data relevant to IL-17’s role in psoriasis pathogenesis. Methods: We performed a Pubmed and Web of Knowledge search for English articles starting from 1990 that discussed the Th17 pathway. Search terms such as “IL-17” and “psoriasis” were utilized. Results: The IL-17 pathway is regulated by IL-23, a cytokine that is vital for the expansion and maintenance of the Th17 cell population. Th17 derived cytokines (IL-17A, IL-17F, IL-17A/F and IL-22) were elevated in both psoriasis-like murine models and human psoriatic lesional biopsies. Ixekizumab (anti-IL-17A) treatment of psoriasis was found to normalize levels of IL-17 downstream gene products. Conclusion: Both preclinical and clinical studies support the central role of IL-17 in the pathogenesis of psoriasis.

Enhancing Patient Satisfaction in Dermatology

Patient satisfaction is an important component of dermatological care that reflects patients’ perspectives on the care they receive. While physicians’ expertise and judgment should always remain the foundation of providing appropriate and effective care, the patient experience can also be influenced by interpersonal relationships, expectations, and a sense of agency in the treatment patients receive. Dermatology providers can use practical techniques such as sitting rather than standing, reframing the concept of cure, and engaging patients in treatment decisions to improve the patient–provider experience and thereby optimize patient satisfaction.

Supraerythemogenic excimer laser in combination with clobetasol spray and calcitriol ointment for the treatment of generalized plaque psoriasis: Interim results of an open label pilot study.

Abstract Background: The combination of phototherapy and topical therapy is one of the most widely used treatment modalities for moderate to severe psoriasis. The development of targeted phototherapy with excimer laser and new topical spray formulations has made these therapies both more convenient and more effective. In this open label pilot study, we aim to assess the efficacy of combination therapy using 308-nm excimer laser, clobetasol propionate spray and calcitriol ointment for the treatment of moderate to severe generalized psoriasis. Methods: In this 12-week study, patients with moderate to severe psoriasis received twice weekly treatment with XTRAC® Velocity 308-nm excimer laser combined with clobetasol propionate twice daily followed by calitriol ointment twice daily. Results: To date, 21 patients have completed the protocol. By week 12, 76% of the patients had a reduction in Psoriasis Area and Severity Index by at least 75% (PASI-75) and 52% had a Physicians Global Assessment of “clear” or “almost clear”. Conclusions: Excimer laser therapy combined with an optimized topical regimen that includes clobetasol spray followed by calictriol ointment appears to be an effective treatment for moderate to severe generalized psoriasis that avoids the risk of serious internal side effects associated with many systemic agents.

The Spectrum of Ideation in Patients with Symptoms of Infestation: From Overvalued Ideas to the Terminal Delusional State

Delusional infestation (DI) is a type of monosymptomatic hypochondriacal psychosis characterized by the steadfast belief that one is infested with living organisms or inanimate material in the absence of objective proof. Although DI is generally regarded as a single psychotic phenotype characterized by either the presence or absence of a delusion, our experience has been that patients with DI present with varying levels of severity represented by various phenotypes along a continuum. Distinguishing where a particular patient presents on this spectrum has allowed us to modify our approach with greater sophistication and thereby optimize management. Our aim is to describe for the first time in dermatology the concept of the DI continuum with support from the psychiatric literature, and to provide practical therapeutic recommendations for each phenotype in the spectrum.

The dermatologic intimacy scale: quantitatively measuring the impact of skin disease on intimacy

Abstract Introduction: Patient-reported outcome measures are increasingly utilized in dermatology to assess the impact of skin disease on quality of life. Despite recognition of the influence of skin disease on intimate relationships, an instrument to assess intimacy has not been developed. The objective of this study was to create the dermatologic intimacy scale (DIS) and administer the prototype to a patient population. Methods: A group of healthcare providers at the University of California San Francisco created the DIS prototype. A total of 1676 psoriasis patients of an online community were invited to complete a cross-sectional survey including demographic information, DIS, body surface area (BSA) and anatomical involvement. Results: A total of 1109 patients completed the survey in its entirety. Patients with moderate-to-severe psoriasis (BSA ≥3%) had a higher DIS score overall and for each individual question than patients with mild disease (BSA < 3%; p < .001). Patients with genitalia, nails, face, neck and scalp involvement had higher scores compared to patients without involvement (p < .001). Conclusions: Patients with more extensive disease and specific anatomical involvement experience a greater impact on intimacy. Interpretation is limited by patient response rate, as patients with or without intimacy issues may be more or less likely to respond. Further analysis is necessary for validation and interpretation.

The Correlation between the Dermatology Life Quality Index and the Psoriasis Area Severity Index

Background Psoriasis patients experience a significant decrease in quality of life (QoL). Objectives This study was conducted to prospectively measure changes in QoL of patients with moderate-to-severe psoriasis who are treated with ustekinumab. We performed a review of the literature, and discussed the significance of our results in the context of the controversy regarding the correlation between the Dermatology Life Quality Index (DLQI) and Psoriasis Area Severity Index (PASI). Methods Seventeen patients with moderate-to-severe plaque psoriasis received 36 weeks of ustekinumab and were followed every 4 weeks. Results All patients demonstrated significant improvement, both in terms of QoL and physical assessments. The data suggest a strong linear correlation between mean percent reduction in PASI and mean reduction in DLQI (R2=0.94). Conclusion Psoriasis patients treated with ustekinumab achieved significant improvement of QoL, which correlated with physical improvement. This study demonstrates a strong correlation between mean percent reduction in PASI and mean reduction in DLQI.

Safety and Efficacy of Combining Biologic with Nonbiologic Therapies for Moderate to Severe Psoriasis: A Review

Background Some psoriasis patients respond inadequately to monotherapy and require combination therapy. Combining a biologic and nonbiologic agent may provide improvement. Objective To review the efficacy and safety of combination treatment with biologic and nonbiologic agents in the treatment of moderate to severe plaque psoriasis. Methods We searched Pubmed for English-language publications evaluating combination treatment with biologic and nonbiologic therapies through June 2014. Results Etancercept was the most commonly used biologic followed by ustekinumab, adalimumab, and infliximab. The majority of nonbiologic therapies reported were narrowband UVB (NBUVB) and methotrexate. Most cases reported increased efficacy with combination therapy with serious adverse events occurring in less than 3% of patients. Conclusion Combination biologic plus nonbiologic therapy, especially NBUVB with biologics is a viable clinical strategy in the treatment of psoriasis patients unresponsive to monotherapy, despite limitations in the data available. However, the long-term impact of these combinations has yet to be determined.

How to optimally manage unhappy, anxious, and difficult patients ☆

Patient satisfaction has been and is of growing importance in healthcare. Recent healthcare initiatives aim to provide physicians with performance feedback reports based partially on patient completed surveys; thus, patient satisfaction will be an even more important determinant of high quality care. In the field of dermatology, patient satisfaction is particularly relevant and at times difficult to achieve, since many patients are plagued with chronic skin diseases often requiring intensive topical regimens or undesirable systemic immunosuppressants. The discussion of patient satisfaction is usually restricted to encounters with the general clinic population leaving encounters with difficult patients largely underreported; therefore, we provide examples of more common difficult patient encounters a dermatologist may face with specific recommendations on how to best optimize patient satisfaction.