Jensen Yeung

Adverse events resulting in withdrawal of biologic therapy for psoriasis in real-world clinical practice: A Canadian multicenter retrospective study

BACKGROUND Safety profiles of biologics for treatment of psoriasis are limited to data from randomized controlled trials. There is a need for comparative safety reports of biologics based on data from clinical practice. OBJECTIVE We sought to estimate and compare the incidence of adverse events (AEs) leading to withdrawal of biologics (etanercept, infliximab, adalimumab, and ustekinumab) in the treatment of psoriasis. METHODS We conducted a multicenter retrospective chart review from September 2005 to September 2014. Incidence proportion and rate of AEs leading to withdrawal by biologic agent and AE were calculated. RESULTS For 545 treatments administered in 398 patients, 22 (4.04%) AEs were associated with withdrawal, for a rate of 1.97/100 patient-years (95% confidence interval [CI] 1.32-2.94). Common AEs were injection-/infusion-site reactions (0.55%, 0.92%, 0%, and 0% for etanercept, infliximab, adalimumab, and ustekinumab, respectively); infections (0%, 0.18%, 0.55%, 0.18%); and malignancies (0.18%, 0.18%, 0%, 0.37%). LIMITATIONS Possible incompleteness of chart details and small study population limit the conclusiveness of findings. CONCLUSION Biologic agents for treatment of psoriasis are safe; AEs associated with withdrawal occurred in 4% of all administered biologic therapies. It does not appear that real-world patients encounter more AEs with biologics than patients in clinical trials.

Short-term reasons for withdrawal and adverse events associated with apremilast therapy for psoriasis in real-world practice compared to clinical trials: a multicenter retrospective study

To the Editor: Psoriasis management relies on long-term therapies that control symptoms and reduce disease manifestations. Apremilast is a safe and effective agent for treating psoriasis according to its randomized controlled trials (RCTs), ESTEEM 1 and 2. However, it is important to evaluate apremilast’s safety in real-world practice (RWP) because RCTs are primarily powered to measure efficacy. Hence, institutions such as the US Food and Drug Administration often rely on real-world postmarketing safety surveillance when approving regulatory actions. We evaluated the short-term reasons for withdrawal and safety of apremilast in RWP compared with in RCTs. A retrospective review of 208 patients was conducted at 2 academic hospitals. The project was approved by the research ethics board of Women’s College Hospital and Sunnybrook Health Sciences Centre. Patients with psoriasis who were treated with apremilast and at least 18 years old were included. Patients were permitted to use concurrent therapies alongside apremilast. Safety (reported adverse events [AEs]) and tolerability (withdrawal due to AEs) were assessed from baseline to week 16. The Pearson test was used to compare outcomes between patients in RWP and RCTs (P # .05 was considered significant). Our results demonstrated that fewer patients in RWP reported 1 or more AEs than did patients in RCTs (58.7% in RWP vs 68.9% in an RCT [P 1⁄4 .005]) (Table I). However, many common AEs reported in RWP were shown in proportions similar to those reported in RCTs: diarrhea (P 1⁄4 .624), headache (P1⁄4 .298), and nausea (P1⁄4 .447). In all, 39 patients in RWP withdrew treatment on account of AEs, and this number was proportionately greater than in RCTs (18.8% in RWP vs 5.3% in an RCT [P \ .001]) (Table II). Accordingly, many AEs leading to withdrawal in RWP were reported in greater proportions than in RCTs: diarrhea (P1⁄4 .001), nausea (P 1⁄4 .004), and headache (P\ .001). These real-world findings support the apremilast RCT data. Most patients in RWP experiencedmild-tomoderate AEs similar to those experienced by patients in RCTs: diarrhea (P 1⁄4 .624), headache (P 1⁄4 .298), and nausea (P 1⁄4 .447). Moreover, we had no reports of tuberculosis reactivation, malignancy, opportunistic infections, or life-threatening AEs. In fact, the proportion of patients in RWP who experienced 1 or more AEs was lower than in RCTs (P 1⁄4 .005). This may be explained by the fact that AEs were not actively elicited in RWP, as reflected by our lower proportion of reports of upper respiratory tract infection (P 1⁄4 .003). As expected, there were proportionately more withdrawals in RWP than in RCTs (P \ .001). The real-world AEs resulting in discontinuation paralleled those in RCTs but were reported in greater proportions: diarrhea (P 1⁄4 .001), nausea (P 1⁄4 .004), and headache (P \ .001). These larger withdrawal proportions can be attributed to several factors. First, most patients in RWP had insurance coverage, allowing them to easily switch medications. Second, patients in RCTs generally had more frequent clinical visits, which encouraged tolerability. Third, proportionately more patients in RWP had failed a prior systemic/biologic therapy (P \ .001), implying they had more challenging psoriasis and the disadvantages associated with AEs may have outweighed the therapeutic benefits of apremilast. Overall, this study suggests that patients with psoriasis in RWP who were using apremilast expectedly reported less tolerability compared with patients in RCTs and may have experienced proportionately fewer mild-to-moderate AEs, bearing in mind that AEs were not actively elicited in RWP.

Current Status and Future of Skin Substitutes for Chronic Wound Healing.

Chronic wounds, including diabetic ulcers, pressure ulcers, venous ulcers, and arterial insufficiency ulcers, are both difficult and expensive to treat. Conventional wound care may sometimes lead to suboptimal wound healing and significant morbidity and mortality for patients. The use of skin substitutes provides an alternative therapy showing superior efficacy and, in some cases, similar cost-effectiveness compared to traditional treatments. This review discusses the different types of currently available commercial skin substitutes for use in chronic wounds as well as the paucity of strong evidence supporting their use. It then delves into the limitations of these skin substitutes and examines the most recent research targeting these limitations.

Survival rates of biological therapies for psoriasis treatment in real-world clinical practice: A Canadian multicentre retrospective study

Data on biologic drug survival in real‐world psoriasis treatment are limited. There is a need to evaluate long‐term trends of biologic use outside the realm of clinical trials.

Efficacy and safety of secukinumab in treating moderate to severe plaque psoriasis in two real‐world Canadian dermatology clinics: a multicenter retrospective study

diomyopathy during therapy with dabrafenib and trametinib. When myocarditis was first reported during treatment with dabrafenib and trametinib, a warning was published by the European Medicine Agency and myocarditis added to the serious side-effects. Differential diagnoses of myocarditis include infectious, immune-mediated and toxic causes. Granulomatous infiltration in the heart may be associated with rheumatic fever, metabolic disorders, sarcoidosis, Wegener’s granulomatosis, giant cell myocarditis and infectious diseases such as tuberculosis. In our case, autopsy confirmed inconspicuous heart valves, and no infectious focus was found. Moreover, sarcoidosis or rheumatoid arthritis was judged less probable, as there was no evidence of these generally systemic diseases. To recognize significant cardiac impairment during targeted therapy, echocardiography is recommended at baseline, after 1 month, and every 2–3 months thereafter. Our patient did not reveal any cardiac complaints or impairment. Increased CK is a common, frequently asymptomatic side effect of MEK inhibitors. However, based on our report we suggest to further investigate persistent elevation of CK during targeted therapy to rule out myocarditis. Altogether, our report contributes to expand knowledge about rare side-effects associated with contemporary oncological treatment.

Drug survival of secukinumab in real-world plaque psoriasis patients: A 52-week, multicenter, retrospective study

REFERENCES 1. Sahni K, Parsad D. Stability in vitiligo: is there a perfect way to predict it? J Cutan Aesthet Surg. 2013; 6:75-82. 2. Parsad D, Gupta S. Standard guidelines of care for vitiligo surgery. Indian J Dermatol Venereol Leprol. 2008;74(Suppl S1): 37-45. 3. Li W, Wang S, Xu AE. Role of in vivo reflectance confocal microscopy indetermining stability in vitiligo: a preliminary study. Indian J Dermatol. 2013;58:429-432. 4. Chuh AA, Zawar V. Demonstration of residual perifollicular pigmentation in localized vitiligo-a reverse and novel application of digital epiluminescence dermoscopy. Comput Med Imaging Graph. 2004;28:213-217. 5. Meng R, Zhao G, Cai RK, Xiao M, Jiang Z. Application of polarized light dermoscopy in the early diagnosis of vitiligo and its differential diagnosis from other depigmented diseases. Chinese J Dermatol. 2009;42:810-813.

A comparison of apremilast monotherapy and combination therapy for plaque psoriasis in clinical practice: A Canadian multicenter retrospective study

REFERENCES 1. Kubica AW, Brewer JD. Melanoma in immunosuppressed patients. Mayo Clin Proc. 2012;87:991-1003. 2. Pratt G, Goodyear O, Moss P. Immunodeficiency and immunotherapy in multiple myeloma. Br J Haematol. 2007;138: 563-579. 3. Yang J, Terebelo HR, Zonder JA. Secondary primary malignancies in multiple myeloma: an old NEMESIS revisited. Adv Hematol. 2012;2012:801495. 4. Dong C, Hemminki K. Second primary neoplasms among 53 159 haematolymphoproliferative malignancy patients in Sweden, 1958-1996: a search for common mechanisms. Br J Cancer. 2001;85:997-1005. 5. Mailankody S, Pfeiffer RM, Kristinsson SY, et al. Risk of acute myeloid leukemia and myelodysplastic syndromes after multiple myeloma and its precursor disease (MGUS). Blood. 2011; 118:4086-4092.

Efficacy and safety of switching to ixekizumab in secukinumab non-responders with plaque psoriasis: a multicenter retrospective study of interleukin (IL)-17A antagonist therapies

REFERENCES 1. Olazagasti JM, Baez PJ, Wetter DA, Ernste FC. Cancer risk in dermatomyositis: a meta-analysis of cohort studies. Am J Clin Dermatol. 2015;16(2):89-98. 2. Yang Z, Lin F, Qin B, Liang Y, Zhong R. Polymyositis/ dermatomyositis and malignancy risk: a metaanalysis study. J Rheumatol. 2015;42(2):282-291. 3. Bohan A, Peter JB. Polymyositis and dermatomyositis ( first of two parts). N Engl J Med. 1975;292(7):344-347. 4. Euwer RL, Sontheimer RD. Amyopathic dermatomyositis: a review. J Invest Dermatol. 1993;100(1):124S-127S. 5. Lu X, Yang H, Shu X, et al. Factors predicting malignancy in patients with polymyositis and dermatomyostis: a systematic review and meta-analysis. PLoS One. 2014;9(4):e94128.

Efficacy and Safety of Apremilast Monotherapy for Moderate to Severe Psoriasis: Retrospective Study :

Background: Apremilast is a new oral drug for the treatment of moderate to severe plaque psoriasis that reduces inflammation by inhibiting phosphodiesterase 4. Its efficacy and safety data are limited; hence, real-world outcomes are important for elucidating the full spectrum of its adverse events (AEs) and expanding generalizability of clinical trial findings. Objective: Assess the efficacy and safety of apremilast monotherapy in real-world practice. Methods: A retrospective chart review was conducted in 2 academic dermatology practices. Efficacy was measured as the proportion of patients achieving a ≥75% reduction from baseline Psoriasis Area and Severity Index score (PASI-75) or a Psoriasis Global Assessment (PGA) score of 0 (clear) or 1 (almost clear) at 16 weeks. Safety was measured as the proportion of patients reporting ≥1 AE at 16 weeks. Results: Thirty-four patients were included. Efficacy: 19 patients (55.9%) achieved PASI-75 or PGA 0/1. Safety: 23 patients (67.6%) experienced ≥1 AEs. Five patients (14.7%) withdrew treatment prior to week 16 due to AEs. One patient withdrew treatment due to mood lability and depression. Common AEs included headache (32.4%), nausea (20.6%), diarrhoea (14.7%), weight loss (8.8%), and loose stool (8.8%). Conclusion: Apremilast monotherapy had higher efficacy with similar safety outcomes in the real world compared to clinical trials. There were higher proportions of reported headaches compared to clinical trials. This study supports the apremilast monotherapy clinical trial findings, suggesting that it has an acceptable safety profile and significantly reduces the severity of moderate to severe plaque psoriasis. Limitations include the retrospective nature of the study.

Pseudoxanthoma Elasticum–Like Papillary Dermal Elastolysis: A Single Case Report

Background: Pseudoxanthoma elasticum–like papillary dermal elastolysis (PXE-PDE), a rare acquired elastolytic disorder, occurs in postmenopausal, elderly women and is characterized by soft, white-yellow papules that localize on the neck and supraclavicular regions and often coalesce into cobblestone plaques. It has no systemic involvement and is histologically distinct from the clinically similar inherited pseudoxanthoma elasticum. Case Summary: A 64-year-old Caucasian woman presented with a 2-year history of multiple, asymptomatic soft yellow 1- to 2-mm papules on her neck, which were increasing in number. On histopathology, haemotoxylin and eosin stain showed a normal-appearing papillary dermis; however, Verhoeff–van Gieson elastic stain showed absent elastic fibres in the papillary dermis. Papular elastorrhexis was suggested, but given its clinical picture, PXE-PDE was also considered. There was no resolution after 2 courses of intralesional triamcinolone acetonide (0.1 mL of 5 mg/mL). Conclusion: PXE-PDE, which is characterized by complete loss or significant reduction of elastic fibres in the papillary dermis, was consistent with our patient’s presentation and histologic findings. Papular elastorrhexis, a paediatric cutaneous disorder, was initially considered, but clinicopathologic correlation led to a diagnosis of PXE-PDE. Intralesional corticosteroids was tried as a treatment but was ineffective at improving the condition. This report documents the importance of histopathology and clinicopathologic correlation when differentiating the overlapping variants of fibroelastolytic disease.