Research Spotlight

Posted May 15th 2020

Efficacy of Risankizumab in Patients with Moderate-to-Severe Plaque Psoriasis by Baseline Demographics, Disease Characteristics and Prior Biologic Therapy: An Integrated Analysis of the Phase III UltIMMa-1 and UltIMMa-2 Studies.

Alan M. Menter M.D.

Alan M. Menter M.D.

Strober, B., A. Menter, C. Leonardi, K. Gordon, J. Lambert, L. Puig, H. Photowala, M. Longcore, T. Zhan and P. Foley (2020). “Efficacy of Risankizumab in Patients with Moderate-to-Severe Plaque Psoriasis by Baseline Demographics, Disease Characteristics and Prior Biologic Therapy: An Integrated Analysis of the Phase III UltIMMa-1 and UltIMMa-2 Studies.” J Eur Acad Dermatol Venereol Apr 22. [Epub ahead of print].

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BACKGROUND: Risankizumab is a humanized IgG monoclonal antibody that selectively inhibits interleukin-23 through binding the p19 subunit. In Phase 3 trials, risankizumab demonstrated superior efficacy compared with adalimumab and ustekinumab in patients with moderate-to-severe plaque psoriasis. Here, we evaluated the impact of baseline characteristics on efficacy of risankizumab compared with ustekinumab in patients with moderate-to-severe plaque psoriasis. METHODS: This analysis included all patients initially randomized to risankizumab or ustekinumab from the replicate, double-blinded, randomized, placebo-controlled phase 3 trials, UltIMMa-1 (NCT02684370) and UltIMMa-2 (NCT02684357). Patients received either risankizumab (150 mg) or ustekinumab (weight-based; 45 or 90 mg per label) at weeks 0, 4, 16, 28, and 40. Efficacy was assessed as the proportion of patients achieving >/=90% improvement in Psoriasis Area and Severity Index (PASI 90) at weeks 16 and 52 by baseline patient demographics, disease characteristics, and prior biologic exposure. Mean percent improvement in PASI was calculated by body weight and body mass index at week 52. Missing efficacy data were imputed as non-responders for categorical variables and last observation carried forward for continuous variables. Logistic regression analyses assessed for interactions between treatment and five independent variables (age, sex, weight, baseline PASI score, and presence of psoriatic arthritis) at both weeks 16 and 52. RESULTS: Baseline patient demographics, disease characteristics and prior biologic exposure were similar between patients randomized to risankizumab (n=598) and ustekinumab (n=199). At weeks 16 and 52, risankizumab demonstrated superior efficacy compared with ustekinumab across these patient characteristics (P<0.01). Logistic regression analyses demonstrated that risankizumab was superior to ustekinumab at weeks 16 and 52 in all models tested (P<0.0001 for all). CONCLUSIONS: Risankizumab demonstrated consistent and superior efficacy compared with ustekinumab regardless of patient demographics, disease characteristics, or prior biologic exposure.


Posted May 15th 2020

To Tweet or Not To Tweet?

John J. Squiers, M.D.

John J. Squiers, M.D.

Squiers, J. J., R. Sells and E. Shih (2020). “To Tweet or Not To Tweet?” Ann Thorac Surg Apr 23. pii: S0003-4975(20)30577-4. [Epub ahead of print].

Full text of this article.

While readers who browse only the title and abstract of this manuscript may be tempted to open a Twitter account and/or increase their Twitter activity in an effort to broaden their academic profile, we would point out that other equally effective options seem to be to remain off Twitter or to shut down an already existing Twitter account. Ultimately, the role of Twitter in academic surgery may evolve, but, for now at least, Twitter-less thoracic surgeons can rest easy having chosen “Not To Tweet”. (Excerpt from text; no abstract available.)


Posted May 15th 2020

Reducing Antibiotic Use in Ambulatory Care through Influenza Vaccination.

Manjusha Gaglani M.D.

Manjusha Gaglani M.D.

Smith, E. R., A. M. Fry, L. A. Hicks, K. E. Fleming-Dutra, B. Flannery, J. Ferdinands, M. A. Rolfes, E. T. Martin, A. S. Monto, R. K. Zimmerman, M. P. Nowalk, M. L. Jackson, H. Q. McLean, S. C. Olson, M. Gaglani and M. M. Patel (2020). “Reducing Antibiotic Use in Ambulatory Care through Influenza Vaccination.” Clin Infect Dis Apr 23. pii: ciaa464. [Epub ahead of print].

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BACKGROUND: Improving appropriate antibiotic use is crucial for combating antibiotic resistance and unnecessary adverse drug reactions. Acute respiratory illness (ARI) commonly causes outpatient visits and accounts for ~41% of antibiotics used in the United States (U.S.). We examined the influence of influenza vaccination on reducing antibiotic prescriptions among outpatients with ARI. METHODS: We enrolled outpatients aged >/=6 months with ARI from 50-60 U.S. clinics during five winters (2013-2018) and tested for influenza with RT-PCR; results were unavailable for clinical decision-making and clinical influenza testing was infrequent. We collected antibiotic prescriptions and diagnosis codes for ARI syndromes. We calculated vaccine effectiveness (VE) by comparing vaccination odds among influenza-positive cases to test-negative controls. We estimated ARI visits and antibiotic prescriptions averted by influenza vaccination using estimates of VE, coverage, and prevalence of antibiotic prescriptions and influenza. RESULTS: Among 37,487 ARI outpatients, 9,659 (26%) were influenza-positive. Overall, 36% of ARI and 26% of influenza-positive patients were prescribed antibiotics. The top three prevalent ARI syndromes included: viral upper respiratory tract infection (47%), pharyngitis (18%), and allergy or asthma (11%). Among patients testing positive for influenza, 77% did not receive an ICD-CM diagnostic code for influenza. Overall, VE against influenza-associated ARI was 35% (95%CI 32-39). Vaccination prevented 5.6% of all ARI syndromes, ranging from 2.8% (sinusitis) to 11% (clinical influenza). Influenza vaccination averted 1 in 25 (3.8%; 95%CI 3.6%-4.1%) antibiotic prescriptions among ARI outpatients during influenza seasons. CONCLUSION: Vaccination and accurate influenza diagnosis may curb unnecessary antibiotic use and reduce the global threat of antibiotic resistance.


Posted May 15th 2020

The validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD): The development and reliability testing of a novel clinical outcome measurement instrument for the severity of atopic dermatitis.

Alan M. Menter M.D.

Alan M. Menter M.D.

Simpson, E., R. Bissonnette, L. F. Eichenfield, E. Guttman, B. King, J. I. Silverberg, L. A. Beck, T. Bieber, K. Reich, K. Kabashima, M. Seyger, E. Siegfried, G. Stingl, S. R. Feldman, A. Menter, P. van de Kerkhof, G. Yosipovitch, C. Paul, P. Martel, A. Dubost-Brama, J. Armstrong, R. Chavda, S. Frey, Y. Joubert, M. Milutinovic, A. Parneix, H. D. Teixeira, C. Y. Lin, L. Sun, P. Klekotka, B. Nickoloff, Y. Dutronc, L. Mallbris, J. M. Janes, A. M. DeLozier, F. Nunes and A. S. Paller (2020). “The validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD): The development and reliability testing of a novel clinical outcome measurement instrument for the severity of atopic dermatitis.” J Am Acad Dermatol Apr 25. pii: S0190-9622(20)30720-9. [Epub ahead of print].

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BACKGROUND: An Investigator Global Assessment (IGA) is recommended by health agencies for drug registration in atopic dermatitis (AD). Current IGA scales lack standardization. OBJECTIVES: To develop an IGA scale, training module, and clinical certification exam for use in AD trials, and establish content validity and assess reliability. METHODS: Expert dermatologists participated in the development of the validated IGA for AD (vIGA-AD). Reliability (inter-rater and intra-rater) was assessed by 2 web-based surveys. Clinical certification for investigators consisted of a training module and exam. RESULTS: Expert consensus was achieved around a 5-point IGA scale including morphological descriptions, and content validity was established. Survey 1 showed strong inter-rater reliability (Kendall’s coefficient of concordance W [Kendall’s W] = 0.809, intra-class correlation [ICC] = 0.817) and excellent agreement (weighted Kappa = 0.857). Survey 2, completed 5 months after training of dermatologists, showed improvements in scale reliability (Kendall’s W = 0.819, ICC = 0.852, weighted Kappa = 0.889). In this study 627 investigators completed vIGA-AD training and certification. LIMITATIONS: Ratings were assessed on photographs. CONCLUSION: A validated IGA scale and training module were developed with the intent of harmonizing assessment of disease severity in AD trials. Strong reliability and excellent agreement between assessments were observed.


Posted May 15th 2020

Impact of Reappraisal of Fluoroquinolone Minimum Inhibitory Concentration Susceptibility Breakpoints in Gram-Negative Bloodstream Isolates.

Matthew M. Brigmon, M.D.

Matthew M. Brigmon, M.D.

Shealy, S. C., M. M. Brigmon, J. A. Justo, P. B. Bookstaver, J. Kohn and M. N. Al-Hasan (2020). “Impact of Reappraisal of Fluoroquinolone Minimum Inhibitory Concentration Susceptibility Breakpoints in Gram-Negative Bloodstream Isolates.” Antibiotics (Basel) 9(4).

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The Clinical Laboratory Standards Institute lowered the fluoroquinolone minimum inhibitory concentration (MIC) susceptibility breakpoints for Enterobacteriaceae and glucose non-fermenting Gram-negative bacilli in January 2019. This retrospective cohort study describes the impact of this reappraisal on ciprofloxacin susceptibility overall and in patients with risk factors for antimicrobial resistance. Gram-negative bloodstream isolates collected from hospitalized adults at Prisma Health-Midlands hospitals in South Carolina, USA, from January 2010 to December 2014 were included. Matched pairs mean difference (MD) with 95% confidence intervals (CI) were calculated to examine the change in ciprofloxacin susceptibility after MIC breakpoint reappraisal. Susceptibility of Enterobacteriaceae to ciprofloxacin declined by 5.2% (95% CI: -6.6, -3.8; p < 0.001) after reappraisal. The largest impact was demonstrated among Pseudomonas aeruginosa bloodstream isolates (MD -7.8, 95% CI: -14.6, -1.1; p = 0.02) despite more conservative revision in ciprofloxacin MIC breakpoints. Among antimicrobial resistance risk factors, fluoroquinolone exposure within the previous 90 days was associated with the largest change in ciprofloxacin susceptibility (MD -9.3, 95% CI: -16.1, -2.6; p = 0.007). Reappraisal of fluoroquinolone MIC breakpoints has a variable impact on the susceptibility of bloodstream isolates by microbiology and patient population. Healthcare systems should be vigilant to systematically adopt this updated recommendation in order to optimize antimicrobial therapy in patients with bloodstream and other serious infections.