December 14, 2018

The ability of secukinumab vs placebo to clear nail psoriasis was evaluated using the Nail Psoriasis Severity Index.

Patients with moderate to severe nail psoriasis experienced clinically meaningful efficacy and significant quality of life improvements with secukinumab treatment, according to study results published in the British Journal of Dermatology.

Researchers in this placebo-controlled, double-blind, randomized study (TRANSFIGURE) evaluated the efficacy of secukinumab (both 150 mg and 300 mg) compared with placebo for moderate to severe plaque and nail psoriasis for a total of 132 weeks. Presented in this publication were the results from the week 32 interim analysis. This time period was chosen because fingernails typically take approximately 6 months to fully grow out to the distal edge from the nail matrix.

A total of 198 study participants were randomly assigned into a placebo group (n=65), a secukinumab 150 mg group (n=67), and a secukinumab 300 mg group (n= 66). The ability of secukinumab vs placebo to clear nail psoriasis was evaluated using the Nail Psoriasis Severity Index (NAPSI), quality of life improvements were evaluated using Nail Assessment in Psoriasis and Psoriatic Arthritis questionnaires on quality of life (NAPPA-QOL), and skin clearance was measured by the baseline Psoriasis Area and Severity Index (PASI).

At week 16, both secukinumab doses were superior to placebo (-10.8% NAPSI improvement for placebo, -37.9% for 150 mg secukinumab, and -45.3% for 300 mg secukinumab; P <.0001). Significant quality of life improvements were also seen at 16 weeks (NAPPA-QOL median scores decreased by 15.8% for placebo, 49.9% for secukinumab 150 mg, and 60.9% for secukinumab 300 mg; P <.0001).

These improvements continued through week 32 (-52.6% NAPSI improvement for 150 mg secukinumab and -63.2% for 300 mg secukinumab). Significant skin clearance was observed at week 16 (PASI 90: 1.7% for placebo and 54.0% and 72.5% for secukinumab 150 mg and 300 mg, respectively; P <.0001) and was sustained through week 32. Headache, upper respiratory tract infections, and nasopharyngitis were the most frequent adverse events, and they were not dose-related. Serious adverse events were rare and non-fatal.  

The investigators conclude that “TRANSFIGURE provides some of the most compelling evidence yet in the difficult to treat population of nail psoriasis, evidence of significant efficacy and meaningful improvements in patients’ [quality of life]. Secukinumab thus offers an effective treatment option for subjects with moderate to severe nail psoriasis.”

Disclosure: Funding and assistance for this study were provided by Novartis Pharmaceuticals. See reference for complete disclosure information. 

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Reference

Reich K, Sullivan J, Arenberger P, et al. Effect of secukinumab on clinical activity and disease burden of nail psoriasis: 32-week results from the randomized placebo-controlled TRANSFIGURE trial [published online October 26, 2018]. Br J Dermatol. doi: 10.1111/bjd.17351

December 14, 2018

Pregnant women are considered a “vulnerable” population in the eyes of clinical researchers.

In clinical research, pregnant women are considered a “vulnerable” population, due to the presence of a fetus who cannot consent to participation.¹ To obtain ethical committee approval, clinical study interventions must “[either] directly benefit [or] pose minimal risk to the mother and fetus.” In addition, consent often must be obtained from both parents.

These stringent inclusion criteria for pregnant women frequently preclude clinical trial participation. For this reason, more than 80% of pregnant patients are prescribed therapies that have not been studied in pregnancy.² In a Viewpoint piece published in JAMA,³ Drs Katrina Heyrana, Heather M Byers, and Pamela Stratton from the National Institutes of Health (NIH) in Bethesda, Maryland, advocated for the increased inclusion of pregnant women in clinical trials so that pregnant patients may have equitable access to evidence-based medicine.

In the 1960s and 1970s, clinical trials assessing the efficacy of pharmaceuticals in pregnant women led to unintended consequences for exposed fetuses. Specifically, birth defects following in utero exposure to thalidomide and diethylstilbestrol compelled the US Food and Drug Administration (FDA) to develop policies protecting “female research participants of reproductive age from [teratogens exposure].”¹ However, the investigators wrote, these guidelines initiated a legacy of excluding pregnant women from clinical trials altogether. In the 1990s, the US Food and Drug Administration (FDA) and NIH expanded on existing guidelines, stipulating that research must include female participants in the absence of any “convincing reason for…exclusion.” The Centers for Disease Control and Prevention and the NIH later released recommendations for the inclusion of pregnant women specifically, but these recommendations have lagged, the investigators wrote.⁴ Of the 213 new pharmaceuticals receiving FDA approval from 2003 to 2012, only 5% included any data from pregnant women.¹

Modern concerns regarding the Zika virus have reignited conversations surrounding the inclusion of pregnant women in clinical trials. Despite the disproportionate burden of Zika virus in pregnant women and fetuses, none of the trials of Zika virus vaccine candidates have included pregnant women.⁵ Investigating means of intervention in pregnant populations is essential to curbing Zika incidence, the researchers wrote. If provided “adequate counseling about…conditions and treatment options,” thus, pregnant women should have full capacity to make decisions regarding trial participation.

The investigators emphasized the necessity of “clear, actionable guidelines” for the inclusion of pregnant women in clinical research and addressed 3 subsequent barriers to this achievement. First, they dismissed the characterization of pregnant women as a “vulnerable” population. The researchers instead suggested reclassifying pregnant women as “scientifically complex,” in an effort to acknowledge the autonomy and decision-making capacity of their population.⁵

Second, federal regulations do not define “acceptable risk” to a woman or fetus; per the Common Rule, risk must not exceed that which may be “encountered in daily life or during…medical examinations.”¹ However, these parameters are imprecise: acceptable risk levels may be mediated by the patient’s perceptions and opinions, as well as the urgency of the clinical scenario. Acceptable risk levels must be standardized to facilitate trial participation, the investigators wrote.

Finally, the perceived legal risk following a maternal or fetal adverse outcome has an impact on the willingness of practitioners to perform research in pregnant women. Per a 2015 survey, nearly 73.6% of 4295 obstetricians reported being implicated in a malpractice lawsuit.⁶ This barrier could be mitigated by standardizing informed consent procedures. The researchers further suggested “partnerships with community leaders and ethical and legal experts” so that enrollees receive culturally competent and accessible information regarding study risks. Beyond all other considerations, they emphasized the autonomy of pregnant women and their capacity to make informed decisions when provided adequate counsel and opportunity. The need for adequately researched interventions in this population necessitates their inclusion to allow them to make informed medical decisions, a right afforded to all other patient populations.

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References

1. US Department of Health and Human Services. Protection of human subjects. www.hhs.gov/ohrp/sites/default/files/ohrp/humansubjects/regbook2013.pdf. 2009. Accessed December 3, 2018.
2. Ayad M, Costantine MM. Epidemiology of medications use in pregnancy. Semin Perinatol. 2015;39(7):508-511. doi:10.1053/j.semperi.2015.08.002
3. Heyrana K, Byers HM, Stratton P. Increasing the participation of pregnant women in clinical trials [published online November 7, 2018]. JAMA. doi:10.1001/jama.2018.17716
4. Foulkes MA, Grady C, Spong CY, Bates A, Clayton JA. Clinical research enrolling pregnant women: a workshop summary. J Womens Health (Larchmt). 2011;20(10):1429-1432.
5. Ethics Working Group on ZIKV Research and Pregnancy. Pregnant women and the Zika virus vaccine research agenda: ethics guidance on priorities, inclusion, and evidence generation. http://guidance.zikapregnancyethics.org/wpcontent/uploads/2017/08/Full+Guidance-Pregnant-Women-the-Zika-Virus-Vaccine-Research-Agenda_optimized.pdf. Accessed December 3, 2018.
6. Carpentieri AM, Lumalcuri JL, Shaw J, Joseph GF. Overview of the 2015 American Congress of Obstetricians and Gynecologists’ survey on professional liability. https://www.acog.org/-/media/Departments/Professional-Liability/2015PL SurveyNationalSummary11315.pdf. Published November 3, 2015. Accessed December 3, 2018.

December 14, 2018

Clinical morphologic testing in addition to tissue biopsy and culture are critical in distinguishing NND from NF and treating appropriately.

Lack of sufficient diagnostic criteria and biomarkers for distinguishing necrotizing neutrophilic dermatosis (NND) from necrotizing fasciitis (NF) may lead to inappropriate treatment that worsens the actual condition and prolongs disease morbidity, according to a study published in JAMA Dermatology.

In a case series of 54 patients diagnosed with NND at 3 academic institutions (University of California San Francisco, Oregon Health and Science University, and University of Minnesota) from January 1, 2015 to December 31, 2017, investigators found that 51 (94%) cases of NND were initially misdiagnosed as NF, resulting in patients receiving inappropriate treatment.

Of all the patients in the sample, 40 had pyoderma gangrenosum with systemic inflammation and 14 had necrotizing Sweet syndrome, both of which can mimic sepsis from severe infection (displaying symptoms of fever, leukocytosis, tachycardia, hypotension, and organ failure). The researchers found hematologic disorders and malignant neoplasms to be the most common disease associations in all 54 patients (n=18 [33%]), with myelodysplastic syndrome occurring in 9 patients (17%). Connective tissue disease (n=6 [11%]), endocrine disorders (n=7 [13%]), and inflammatory bowel disease (n=6 [11%]) were other common comorbidities. Potential medication triggers occurred in 7 patients (13%).

The most common cutaneous finding was erythema (n=41 [76%]), followed by other common findings of ulcers (n=25 [46%]) and necrosis (n=16 [30%]). Systemic findings included febrility (n=36 [67%]) and presentation of clinical signs resembling septic shock (n=14 [26%]). Cultures were taken in 45 cases (83%), of which 98% were negative. Elevated markers of systemic inflammation were found in 23 patients (43%), of leukocytosis in 36 patients (67%), and of leukomoid reaction in 15 patients (28%), with a mean (range) white blood cell count of 51371/μL (32,300-138,000/μL). 

The researchers also noted that “typical histopathologic findings were sparse diffuse subcutaneous and dermal inflammation with a predominance of neutrophils as well as associated leukocytoclasis and edema.” In 43% of cases, the neutrophilic infiltrate and associated necrosis often extended to the level of fascia or muscle.

Treatment therapies utilized in patients included debridement (n=42 [78%]), antibiotics (n=49 [91%]), systemic corticosteroids (n=50 [93%]), and limb amputations (n=4 [7%]). Additional immunosuppressants were used with some patients.

These findings suggest that clinical morphologic testing in addition to tissue biopsy and culture are critical in distinguishing NND from NF and treating appropriately.

This study design was limited by reliance on case reviews that were limited by publication bias of poor outcomes and missing information that affects results as well as by clinical descriptions of shock without use of formal Systemic Inflammatory Response Syndrome criteria.

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Reference

Sanchez IM, Lowenstein S, Johnson KA, et al. Clinical features of neutrophilic dermatosis variants resembling necrotizing fasciitis [published online October 31, 2018]. JAMA Dermatol. doi:10.1001/jamadermatol.2018.3890

December 13, 2018

The study concentrated on the 5 most common food allergens in the United States: egg, milk, peanut, soy, and wheat.

In patients with atopic dermatitis (AD), families and healthcare providers need to be cognizant of the risks associated with excessive testing and diet manipulation in their attempts to manage the disorder, which includes the loss of tolerance to a particular food when it is removed from the diet. According to the results of a retrospective chart review published in the Annals of Allergy, Asthma & Immunology, the frequency of oral food challenge (OFC) failure in patients who removed foods suspected of being triggers of AD was 13.3%.

The investigators recognized that the removal of foods from the diet in an attempt to manage AD, according to positive allergy tests, may lead to immediate allergic reactions upon reintroduction of that food, so they sought to examine the frequency of OFC failures in foods removed from the diet as suspected AD triggers. They focused on the 5 major food allergens in the United States: egg, milk, peanut, soy, and wheat.

The current study evaluated OFCs for the 5 major food allergens performed between 2008 and 2014 at the allergy clinic of a US children’s hospital. Oral food challenges were offered to patients according to laboratory values and history. Reasons for food avoidance were classified as food allergy (ie, immunoglobulin E-mediated reaction occurring within 2 hours), sensitization only (lack of introduction of the food because of positive test results), and removal of the food because of test results during evaluation of AD.

A total of 442 OFCs were performed, with 20.1% (89/442) considered failures. The reasons patients underwent OFCs were a history of food allergy (72.4% [320/442]), food sensitization without any introduction (17.4% [77/442]), and the presence of AD (102% [45/442]).

Of note, OFC failures in patients with food allergy (21.9% [70/320]), patients with sensitization only (16.9% [13 of 77], and patients with AD (13.3% [6 of 45]) did not differ significantly (P =.63). Wheat was significantly more likely to be avoided than the other 4 food allergens because of concerns about AD (P <.0001).

The investigators concluded that the restriction of foods in an attempt to manage AD must be conducted with caution and close monitoring. Primary care providers need to counsel families on the limits of using allergy testing and diet changes to address AD. Families should be advised to use such measures as skin hydration, topical medications, and emollients to address AD.

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Reference

Eapen AA, Kloepfer KM, Leickly FE, Slaven JE, Vitalpur G. Oral food challenge failures among foods restricted due to atopic dermatitis [published online October 13, 2018]. Ann Allergy Asthma Immunol. doi:10.1016/j.anai.2018.10.012

December 13, 2018

During development trials, 3 of 953 patients developed confirmed causes of drug reaction with eosinophilia and systemic symptoms.

NEW ORLEANS — Early results from an ongoing, multicenter, open-label safety study of cenobamate has found no cases of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome in 1110 patients with epilepsy exposed to cenobamate for at least 6 months, according to research presented at the 72nd American Epilepsy Society Annual Meeting, held November 30 to December 4, 2018.

Patients aged 18 to 70 with uncontrolled focal (partial) seizures taking stable doses of 1 to 3 antiepileptic drugs were enrolled. Testing a hypothesis that a lower starting dose and slower titration rate of cenobamate than those utilized in earlier studies would mitigate the risk for serious cutaneous reactions like DRESS, investigators administered gradually increasing daily doses of cenobamate 12.5 mg, 25 mg, 50 mg, 100 mg, 150 mg, and 200 mg/day at 2-week intervals. Biweekly increments of 50 mg/day to increase dosage to 400 mg/day were allowed.

For the first 16 weeks of the study period, patients visited every 2 weeks and then every 1 to 3 months thereafter. Patients were screened for DRESS monthly with an in-depth review of all hypersensitivity reactions.

Serious adverse events, reported in accordance with local regulatory requirements, were seen in 114 patients (8.5%), and were most commonly seizures that required hospitalization. Other common adverse events included somnolence, dizziness, and fatigue. No cases of DRESS were identified.

A total of 1347 patients had been enrolled at the time of study data cut-off; 269 patients discontinued therapy. Four deaths were reported: sudden death with no autopsy, traumatic intracerebral hemorrhage after a fall, fatal injuries after being struck by a car, and respiratory failure in a participant with Angelman syndrome. 

In addition, no cases of DRESS were reported among the patients exposed to cenobamate for at least 6 months (n=1110) and among all patients exposed to cenobamate. The most common serious adverse event was seizure, as seen in 14 patients (1.0%). The most common treatment-emergent adverse event was reported to be somnolence (28.1%), dizziness (23.65), and fatigue (16.6%); most were mild or moderate in severity. 

These early results suggest that reducing the starting dose and slowing the titration rate of cenobamate may mitigate the risk for DRESS in patients with epilepsy experiencing uncontrolled focal (partial) seizures.

This study was supported by SK Life Science, Inc. Please refer to reference for a complete list of authors’ disclosures.

For more coverage of AES 2018, click here.

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Reference

Sperling M, Klein P, Kamin M. Safety of cenobamate (YKP3089) as adjunctive treatment for uncontrolled partial seizures in a large, multicenter, open-label study. Presentation at: 72nd Annual Meeting of the American Epilepsy Society; November 30-December 4, 2018; New Orleans, LA. Poster 1.303.

December 13, 2018

Investigators evaluated the effect of ixekizumab withdrawal and retreatment in Japanese patients with plaque psoriasis in this single-arm open-label phase 3 study.

In a cohort of Japanese patients with plaque psoriasis who exhibited an initial response to ixekizumab, approximately half of the patients relapsed within 5 months of treatment withdrawal. Most of these patients subsequently recaptured their responses within 12 weeks, and that response was maintained for up to 120 weeks of retreatment. The results of the single-arm open-label phase 3 study (UNCOVER-J; ClinicalTrials.gov identifier: NCT01624233) were published in the Journal of the European Academy of Dermatology and Venereology.

The investigators sought to evaluate the clinical course after ixekizumab treatment withdrawal and retreatment and the efficacy of retreatment with ixekizumab in Japanese patients with plaque psoriasis. Efficacy measures included the percentage of patients attaining baseline reduction in the Psoriasis Area and Safety Index of 75% (PASI 75), 90% (PASI 90) and 100% (PASI 100); percentage of patients achieving Static Physician Global Assessment 0, 1, and 0; time to relapse (ie, loss of response: PASI ≤50) after ixekizumab withdrawal in patients with a PASI 75 response at week 52; change from baseline in PASI scores; Dermatology Life Quality Index; and Psoriasis Scalp Psoriasis Index (in patients with scalp psoriasis at baseline).

Safety measures included drug-free emergent adverse events (AEs), treatment-emergent AEs, AEs of special interest, serious AEs, AEs that led to treatment discontinuation, and immunogenicity.

A total of 78 patients with plaque psoriasis were enrolled in the study. After ixekizumab treatment (ie, 160-mg loading dose, 80 mg every 2 weeks for the first 12 weeks, and then 80 mg every 4 weeks until week 52), 70 participants attained a PASI 75 response at week 52. These 70 patients were then withdrawn from ixekizumab therapy from week 52 through week 100. The participants who relapsed (PASI ≤50) during the treatment withdrawal period were retreated with 80 mg of ixekizumab every 4 weeks for 192 weeks.

At weeks 52, 76, and 100, PASI 75 response rates were 100%, 26%, and 7%, respectively; PASI 90 response rates were 87%, 11%, and 3%, respectively; and PASI 100 response rates were 53%, 0%, and 0%, respectively. After treatment withdrawal, 87% of patients relapsed, with a median time to relapse of 143 days.

After12 weeks of retreatment with 80 mg of ixekizumab every 4 weeks, 83% of relapsed patients attained PASI 75, 68% attained PASI 90, and 25% attained PASI 100. The improvements were maintained for up to 120 weeks of retreatment.

Treatment-emergent AEs and serious AEs were reported in 56% and 4% of patients, respectively, during the treatment withdrawal period and in 88% and 14% of patients, respectively, during the retreatment period.

The investigators concluded that in patients who were withdrawn from ixekizumab after attaining PASI 75, approximately half relapse within 5 months of withdrawal. Most of these patients recaptured their response within 12 weeks, though, and that response was maintained for up to 120 weeks of retreatment. Interrupted ixekizumab treatment was well tolerated.

The main limitations of this study included the lack of a control group, its open-label design, and that the analysis was conducted in Japanese patients only, with a relatively small sample size.

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Reference

Umezawa Y, Torisu-Itakura H, Morisaki Y, et al; Japanese Ixekizumab Study Group. Long-term efficacy and safety results from an open-label phase III study (UNCOVER-J) in Japanese plaque psoriasis patients: impact of treatment withdrawal and retreatment of ixekizumab [published online October 16, 2018]. J Eur Acad Dermatol Venereol. doi:10.1111/jdv.15292

December 12, 2018

Wikipedia is frequently used as a starting point for health-focused research.

With the proliferation of online medical information, educators and students alike struggle to discern the legitimacy of “e-health” sources.¹ Wikipedia, a crowdsourced online encyclopedia, is frequently utilized as a “starting [point] for locating information” despite its perceived lower quality and reliability compared with peer-reviewed sources.² In fact, 94% of medical students surveyed in 2012 reported using Wikipedia, describing its articles as “easy to access…and understand.”³

Addressing concerns from health professors less familiar with digital resources, Jennifer Meka, PhD, of the Penn State College of Medicine in Hershey, Pennsylvania, developed a framework for incorporating online content into medical education.⁴

Marc Prensky coined the terms “digital natives” and “digital immigrants” to describe individuals who were born into the “digital era” and individuals who were not, respectively.⁵ To properly educate, Mr Prensky asserts, educators must “learn to communicate [with] their students” who are digital natives.⁵ That is, educators must accommodate and regulate students’ use of online materials.

Wikipedia, as a crowdsourced website, is vulnerable to serious errors and thus should be navigated with care. Several studies have investigated the accuracy of Wikipedia. A 2005 study published in Nature compared the accuracy of scientific articles in Wikipedia with those in Encyclopedia Birtannica.⁶ However, an additional review conducted in 2011 found “mixed results.”⁶ 

Even so, medical entries on Wikipedia remain a leading resource, amassing 4.88 billion crowdsourced pageviews in 2013 alone.⁷ In addition, 1 study even suggested that Wikipedia “[complements]…the traditional journal system,” in that scientific articles referenced by Wikipedia receive more citations.⁸ It is clear that despite reservations about scientific accuracy, Wikipedia is frequently utilized by medical students and may even influence the medical research community itself.

As such, researchers developed the Technological Pedagogical Content Knowledge (TPACK) framework to guide educators in “[teaching] effectively with technology.”⁹ TPACK expands on the teachings of Lee Shulman, who emphasized the necessity of “contextual understanding”¹⁰ for educators; in this case, medical professors must be aware that medical learning now occurs in the digital era.

Per TPACK, educators must demonstrate 3 primary forms of knowledge: content knowledge, pedagogical knowledge, and technological knowledge. Through effective utilization of the TPACK framework, educators provide an “optimal learning experience” for digital natives by teaching students to be discerning about online resources. Under TPACK, content knowledge and pedagogical knowledge each reflect standard tenets of teaching; content knowledge comprises understanding of “concepts, theories, ideas” and understanding of their acquisition.¹¹ In a  similar fashion, pedagogical knowledge refers to the understanding of the “materials, programs, and resources” that comprise the curriculum.¹¹ As an addendum, the investigators have added technological knowledge, an understanding of how to productively utilize information technology.⁹ Educators must understand their students’ preferences and needs, specifically the widespread use of Wikipedia and similar sources. By becoming educated on the same online resources utilized by students, educators can effectively provide guidelines and assistance.

Educators must teach students to effectively weigh evidence and make educated decisions, be they in the clinic or performing a resource scan on Wikipedia. Open communication regarding the reliability of these sources is paramount to a proper medical education in the digital era.

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References

1. Eysenbach G. What is e-health? J Med Internet Res. 2001;3(2):e20.
2. Judd T, Kennedy G. Expediency-based practice? Medical students’ reliance on Google and Wikipedia for biomedical inquiries. Br J Educ Technol. 2011;42(2):351-360.
3. Allahwala UK, Nadkarni A, Sebaratnam DF. Wikipedia use amongst medical students—new insights into the digital revolution. Med Teach. 2012:35(4):337.
4. Meka J, Vigliotti A. Should crowdsourced, unvetted content on Wikipedia be used in health sciences teaching and learning? AMA J Ethics. 2018;20(11):E1033-1040
5. Prensky M. Digital natives, digital immigrants. On Horiz. 2001;9(5):1-6.
6. Giles J. Internet encyclopaedias go head to head. Nature. 2005;438(7070):900-901.
7. Heilman JM, West AG. Wikipedia and medicine: quantifying readership, editors, and the significance of natural language. J Med Internet Res. 2015;17(3):e62.
8. Thompson N, Douglas H. Science is shaped by Wikipedia: evidence from a randomized control trial. MIT Sloan School of Management research paper 5238-17. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3039505. Published September 20, 2017. Updated February 19, 2018. Accessed December 3, 2018.
9. Koehler M. TPACK explained [What is TPACK? tab on TPACK website]. http://tpack.org/. Published September 24, 2012. Accessed December 3, 2018.
10. Shulman LS. Knowledge and teaching: foundations of the new reform. Harv Educ Rev. 1987;57(1):1-21.
11. Koehler MJ, Mishra P. What is technological pedagogical content knowledge? Contemp Issues Technol Teach Educ. 2009;9(1):60-70.

December 12, 2018

There was a 2.53-fold increased risk for developing Crohn disease and a 1.71-fold increased risk for developing ulcerative colitis.

Psoriasis is significantly associated with inflammatory bowel disease (IBD), according to a study recently published in JAMA Dermatology.

To investigate the association between psoriasis and IBD, researchers conducted a systematic review and meta-analysis using studies from MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials between inception and January 17, 2018. Investigators included studies that were case-control, cross-sectional, or cohort studies and examined either the odds or risk of IBD in patients with psoriasis. The studies were neither limited geographically nor linguistically. Analyses for Crohn disease and ulcerative colitis were performed separately, and a subgroup analysis on psoriatic arthritis was conducted.

Five case-control or cross-sectional studies and 4 cohort studies with a total of 7,794,087 participants were included. Investigators discovered a significant association between psoriasis and Crohn disease (odds ratio [OR]=1.70, 95% CI, 1.20-2.40) and between psoriasis and ulcerative colitis (OR= 1.75, 95% CI, 1.49-2.05).

Additionally, investigators found an increased risk for Crohn disease and ulcerative colitis in patients with psoriasis (risk ratio=2.53; 95% CI, 1.65-3.89 and risk ratio=1.71; 95% CI, 1.55-1.89, respectively).

Only one cohort study analyzed the relationship between severity of psoriasis and IBD. Due to the variation in sample size across the studies included, the weight of the different studies varied in subgroup analyses. Despite this limitation, the direction of effects was consistent across the analyzed studies. 

The results of this meta-analysis indicate that patients with psoriasis are prone to comorbid Crohn disease and ulcerative colitis. Gastroenterology consultation may be advisable for patients with psoriasis who present with bowel symptoms.

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Reference

Fu Y, Lee CH, Chi CC. Association of psoriasis with inflammatory bowel disease: a systematic review and meta-analysis [published online October 24, 2018]. JAMA Dermatol. doi: 10.1001/jamadermatol.2018.3631

December 12, 2018

The guidelines include a strong recommendation against smoking

A new treatment guideline for psoriatic arthritis (PsA) recommends a treat-to-target approach and the use of tumor necrosis factor inhibitors (TNFi) as a first-line therapy option in patients with active PsA. 

The guideline is jointly authored by the American College of Rheumatology (ACR) and the National Psoriasis Foundation (NPF). It is the first guideline that specifically recommends trying TNFi biologics in treatment-naïve patients first, before using oral small molecule drugs (OSM). 

“The available evidence suggested that in the absence of certain conditions, many treatment-naïve patients would benefit from trying a TNFi biologic first,” said Dafna Gladman, MD, University of Toronto and member of the NPF Medical Board who served as a content expert for the guidelines. She went on to say that OSMs can continue to be used as a first-line option for patients who have contraindications to TNFi treatment or in patients with severe PsA or psoriasis that prefer an oral treatment. 

The guidelines also include a strong recommendation against smoking, as the literature suggests it reduces the efficacy of biologics. 

The authors developed the guidelines using GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology; most of the recommendations were “conditional” because of low or very low quality evidence available in some areas. Principle investigator Jasvinder Singh, MD, called for more head-to-head trials of “various treatments and comparative effectiveness studies in both trial populations and PsA populations with comorbidities.”

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Fore more information visit Rheumatology.org. 

December 12, 2018

The US Food and Drug Administration approved Ipilimumab in 2011.

Increased melanoma care costs as part of skin cancer-related care (SCRC), which includes both skin cancer screening and treatment, were largely due to the increased use and cost of the skin cancer drug ipilimumab at an academic center between 2 time points, according to a recent study published in the Journal of the American Academy of Dermatology.

Researchers determined the costs of SCRC using data from the Dana-Farber/Brigham and Women’s Cancer Center in Boston, Massachusetts in 2008 and 2013. Both insurance and patient payment data were analyzed using the International Classification of Diseases, Ninth Revision. Screening costs were analyzed using Current Procedural Terminology codes. Possible non-normal distribution of the cost data was assessed using Wilcoxon rank sum tests, and chi-square and t tests determined the difference between patient characteristics in 2008 and 2013.

The authors examined data for 9309 patients and 13,514 patients who received SCRC in 2008 and 2013, respectively. There was a 45% increase in skin cancer patient volume. Total treatment cost for melanoma increased by 171% from 3,999,091 to $10,826,138 in 2008 and 2013, respectively).

A t test determined the mean annual cost per skin cancer patient increased by 13% ($1533 to $1731 in 2008 and 2013, respectively [P =.03]). Wilcoxon rank sum tests showed increased melanoma costs at $4405 and $8085 in 2008 and 2013, respectively (84% increase; P <.001).  

In 2013, 48 melanoma patients (4% of total 13,514 patients) were treated with ipilimumab, which costs an average of $95,603 per melanoma patient since the medication was approved by the US Food and Drug Administration (FDA) in 2011. The cost of ipilimumab accounted for 42% of the total costs of melanoma treatment and 20% of the costs of SCRC in 2013. Respective ipilimumab costs were absent in 2008 since the drug was approved for commercial use by the FDA in 2011.

The authors explained that an overall increase in SCRC costs is expected as more skin cancer patients are treated; however, the mean cost per melanoma patient increased significantly and the most among all skin cancers per diagnosis. The authors further explained that despite its high cost, ipilimumab has improved melanoma patients’ overall survival relative to previous standards of care.

Study limitations include the fact that outpatient skin cancer patient prescription costs were unavailable, reimbursement data lacked clinical data (eg, cancer stages and outcomes), and single sum hospital structure payments prevented a broken-down assessment of costs by treatment modality.

The authors stated national studies to monitor the cost-effectiveness SCRC are needed.

Disclosures: Belen Fraile, MD, has received speaker honoraria from Novartis. Patrick A. Ott, MD, has served on the advisory boards of Bristol-Myers Squibb and Merck.

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Reference

Morgan FC, Duran J, Fraile B, et al. A comparison of skin cancer screening and treatment costs at a Massachusetts cancer center, 2008 versus 2013. J Am Acad Dermatol. 2018; 79:921-928.