January 04, 2019

Researchers completed a post hoc analysis of 2 identically designed phase 3 trials to evaluate the efficacy, safety, and tolerability of once-daily dapsone gel, 7.5% for facial acne.

Once-daily dapsone gel, 7.5% is tolerable and effective for the treatment of facial acne in both men and women regardless of baseline lesion count, according to a study published in the Journal of Drugs in Dermatology.

Researchers completed a post hoc analysis of 2 identically designed phase 3 trials to evaluate the efficacy, safety, and tolerability of once-daily dapsone gel, 7.5% when used on facial acne with inflammatory and comedonal lesions. Both trials were 12-week, double-blind randomized studies (Clinicaltrials.gov Identifier: NCT01974141 and NCT01974323). Patients in the treatment arm used dapsone gel on the acne-affected areas once daily, whereas the patients in the control arm applied a vehicle to acne-affected areas oncedaily.

At baseline, patients were categorized into a low lesion count subgroup (50-74), medium lesion count subgroup (75-99), or high lesion count subgroup (≥100). Efficacy was measured by a reduction in the total, inflammatory, and comedonal lesions from baseline to the 12-week follow-up; safety was measured by the incidence of treatment-related adverse events; and tolerability was assessed by rating scales from both patients and clinicians.

Of the 4340 patients enrolled in both trials, 56% were women and 2160 patients were randomly assigned to the treatment arm. At baseline, 1239 patients were in the low lesion count subgroup, 640 patients were in the medium lesion count subgroup, and 281 patients were in the high lesion count subgroup.

Overall, women showed significant improvement of 56.07% in the low lesion count subgroup, 50.22% in the medium lesion count subgroup, and 47.63% in the high lesion count subgroup. Men, on the other hand, had improvements of 47.95%, 42.30%, and 34.68%, respectively.

In regards to inflammatory lesion count, there was a significant improvement among of 60.96% among women in the low lesion count subgroup, 57.91% in the medium lesion count subgroup, and 55.83% in the high lesion count subgroup. Men showed improvements of 52.75%, 46.85%, and 44.70%, respectively.

Regarding comedonal lesion count, women again had a significant improvement over men, with an improvement of 52.96% in the low lesion count subgroup, of 45.40% in the medium lesion count subgroup, and of 44.22% in the high lesion count subgroup compared with 44.67%, 39.38%, and 29.89% among men.

The incidence of treatment-related adverse events was low (18.3%), with the most commonly reported events being nasopharyngitis, headache, upper respiratory tract infection, and application site dryness and pruritus. Burning and stinging were reported by 27.5% of women and 30.3% of men and clinicians reported dryness in 19.6% of women and 15.9% of men, scaling in 16.1% of women and 12.9% of men, and erythema in 25.6% of women and 24.7% of men.

Future studies need to include comparable numbers of men and women and evaluate the relationship between the ratio of comedonal to inflammatory lesions and total lesions.

The researchers concluded “[d]apsone gel, 7.5% was shown to be safe, well tolerated, and effective in this population of females and males with acne, regardless of their baseline total lesion count” with women experiencing the greatest improvement.

Disclosure: This study was supported by Allergan plc. Please refer to reference for a complete list of authors’ disclosures.

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Reference

Tanghetti EA, Harper J, Baldwin HE, Kircik LH, Bai Z, Alvandi N. Once-daily topical dapsone gel, 7.5%: effective for acne vulgaris regardless of baseline lesion count, with superior efficacy in females. J Drugs Dermatol. 2018;17(11):1192-1198.

January 04, 2019

The proportion of participants achieving the primary efficacy endpoint was significantly greater in the oxymetazoline group vs the vehicle group in both trial 1 and trial 2.

Oxymetazoline reduces moderate to severe persistent facial erythema associated with rosacea and is well-tolerated by users, according to a recent study published in the Journal of Drug in Dermatology.

In this study, the researchers conducted a pooled analysis of data from 2 vehicle-controlled, multicenter, double-blind, parallel-group, phase 3 trials (REVEAL; ClinicalTrials.gov Identifier: NCT02131636 and NCT02132117) conducted in the United States from 2014 to 2015.

Study participants (N=885 [440 from trial 1 and 445 from trial 2]) included adults aged 18 and older with moderate to severe persistent facial erythema of rosacea, of which 78.8% were women. Patients were randomly assigned to oxymetazoline or vehicle, which was applied topically to the face once a day for 29 days. Moderate to severe persistent facial erythema of rosacea was defined as a grade 3 or 4 on the Clinician Erythema Assessment (CEA) scale with a photonumeric guide and Subject Self-Assessment for rosacea facial redness (SSA) scale with a photo guide.

The efficacy of oxymetazoline was assessed during each clinic visit during treatment and post-treatment. Primary efficacy assessments were a ≥2-grade decrease (composite success) from baseline on both the CEA and SSA (composite score) at 3, 6, 9, and 12 hours post-dose on day 29. Secondary efficacy assessments were the proportions of patients with a ≥2-grade decrease from baseline on the individual CEA and SSA components, and digital analysis of the percent change from baseline in facial erythema at hours 3, 6, 9, and 12 on day 29.

Most participants (96.3%, 852 participants) completed the trials. The proportion of participants achieving the primary efficacy endpoint was significantly greater in the oxymetazoline group vs the vehicle group in both trial 1 and trial 2 (trial 1, P >.001; trial 2, P =.001). When pooled, the proportion of patients in the in the oxymetazoline group achieving ≥2-grade composite success on both CEA and SSA at hours 3, 6, 9, and 12 on day 29 was 13.1%, 14.4%, 16.6%, and 13.6%, respectively (P ≤.001 for each time point). Respective values in the vehicle group were 6.5%, 6.5%, 7.3%, and 6.0% (P ≤0.001 for each time point). Significantly more patients had ≥2-grade improvement from baseline over the 12-hour observation period on the CEA at day 29 (oxymetazoline group: 390 patients or 87.6%; vehicle group: 395 patients or 90.0%).

The researchers discussed one primary limitation to the 2 trials, which was its short-term treatment period despite the fact that oxymetazoline is a long-term therapy for facial erythema. Despite this limitation, the researchers highlighted the fact that oxymetazoline therapy achieved greater efficacy than and equal tolerability to the vehicle therapy. “Oxymetazoline cream 1.0% applied topically to the face once daily for 29 days effectively reduced moderate to severe erythema of rosacea and was well tolerated,” said the researchers.

Disclosures: Multiple authors declare affiliations with the pharmaceutical industry. Please refer to reference for a complete list of authors’ disclosures.

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Reference

Stein-Gold L, Kircik LH, Draelos ZD, et al. Topical oxymetazoline cream 1.0% for persistent facial erythema associated with rosacea: Pooled analysis of the two phase 3, 29-day, randomized, controlled REVEAL trials. J Drugs Dermatol. 2018;17(11):1201–1208.

January 04, 2019

The popular Keto diet, which focuses on strict carbohydrate limitations and high-fat intake, was ranked at #38

The Mediterranean diet was ranked as the best diet overall for 2019, according to new rankings released by US News and World Report.

An expert panel assessed 41 diets to come up with their final results, examining the evidence behind each diet’s claims, the short-term and long-term weight loss associated with the diet, how easy the diet is to follow, how well each diet conforms to current nutrition standards, and its effect on diabetes and cardiovascular disease prevention.

Diets that rounded out the top 5 spots included the DASH (Dietary Approaches to Stop Hypertension) diet (#2), the Flexitarian diet (a mostly vegetarian diet; #3), the MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) diet (tied for #4), and the Weight Watchers diet (tied for #4).

The popular Keto diet, which focuses on strict carbohydrate limitations and high-fat intake, was ranked at #38, with some experts noting that it could lead to nutritional imbalances and may require medical supervision. Other diets that made the bottom of the list included Whole30 diet (tied for #38), the Body Reset diet (#40), and the Dukan diet (#41), which the experts thought was too restrictive and was not backed by any efficacy evidence.

As for diabetes prevention and management, the Mediterranean diet (#1), DASH diet (tied for #2), Flexitarian diet (tied for #2), Mayo Clinic diet (tied for #2), and Volumetrics (tied for #2) were at the top of the list, while the Mediterranean diet (tied for #1), Ornish diet (tied for #1), and DASH diet (#3) were voted best heart-healthy diets.

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For more information visit USnews.com.

January 03, 2019

Results showed that HS prevalence was increased in patients with psoriasis when compared with the control participants.

There is a significant positive correlation between psoriasis and hidradenitis suppurativa (HS), according to study results recently published in the Journal of the American Academy of Dermatology. The findings of the large-scale study support previous case reports and smaller studies that similarly note the coexistence of psoriasis and HS. 

Investigators completed a cross-sectional population-based study to compare the prevalence of HS in patients with psoriasis across age-, sex-, and ethnicity-matched controls. The study included 68,836 patients with psoriasis and 68,836 control participants.  

Results showed that HS prevalence was increased in patients with psoriasis when compared with the control participants (0.3% vs 0.2% respectively; odds ratio [OR] 1.8; 95% CI, 1.5-2.3; P <.001). When investigators adjusted for smoking, obesity, and other comorbidities in a multivariate analysis, the relationship persisted (OR 1.8; 95% CI 1.4-2.2; P <.001).

Compared with patients with psoriasis alone, those with a dual diagnosis of psoriasis and HS were younger (39.0 ± 15.7 vs 42.6 ± 21.2 years; P =.015), more likely to be obese (35.1% vs 25.3%; P =.001), and were smokers (58.5% vs 37.3%; P <.001). 

Study limitations include a lack of data related to clinical features and severity of both psoriasis and HS. In addition, the classification of socioeconomic status was based on a poverty index rather than household income. Finally, the study was limited to Israeli patients and further longitudinal observational studies are necessary to confirm these findings in other populations. 

Results of the study suggest that physicians treating patients with psoriasis should be mindful of the association between psoriasis and HS, and be aware that systematic therapies that treat both conditions may be preferable in patients with a dual diagnosis. 

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Reference

Kridin K, Shani M, Schonmann Y, et al. Psoriasis and hidradenitis suppurativa: a large-scale population-based study [published online November 28, 2018]. J Am Acad Dermatol. doi: 10.1016/j.jaad.2018.11.036

January 03, 2019

Clindamycin as monotherapy may be a useful and safe alternative to combination clindamycin and rifampicin treatment for hidradenitis suppurativa.

Clindamycin monotherapy may be as or more effective than dual antibiotic treatment for hidradenitis suppurativa (HS) regardless of clinical stage, according to research published in the Journal of the American Academy of Dermatology.

A cohort (N=60) of men and women ≥18 years of age with clinical and sonographic criteria of HS and total abscesses and inflammatory nodule ≥3 at baseline were divided into 2 treatment groups. For a total of 8 weeks, Group A (n=30) was treated with oral clindamycin 150 mg 4 times daily and oral rifampicin 300 mg twice daily; Group B (n=30) was treated with oral clindamycin 150 mg 4 times daily. Researchers performed Power Doppler ultrasound (PD-US) examinations on all patients at baseline and at week 8. The Pulse Repetition Frequency, the Time Gain Compensation, and the Volumetric Image Acquisition were kept constant to reduce PD-US observation limits and statistical mistakes. Researchers analyzed the lesional type of involvement (nodule, abscess, draining tunnel), lesion location, maximum diameter (mm) of the lesion, draining tunnel’s thickness, and presence of vascularization from the sonographic data.

Statistical analysis showed equivalence between the mono and combination therapy groups, with a significant improvement in disease activity found in both groups (P =.598) as assessed by Hidradenitis Suppurativa Clinical Response, International Hidradenitis Suppurativa Severity Score System, PD-US, Pain Visual Analogue Scale, and Dermatology Life Quality Index. Group B had a significantly greater decrease in Pain Visual Analogue Scale (P =.038) and Dermatology Life Quality Index (P =.037) compared with Group A. The count reduction of nodules (P =.517) and of abscesses (P =.938) was not statistically different between the groups. The number of reduced draining tunnels “was statistically more elevated in Group B than in Group A (P =.002),” the researchers noted.

The investigators speculated that “consequent lower clindamycin levels in combined protocols may reduce the strength of the treatment itself in severe HS lesion, as draining tunnels are commonly colonized by polymorph-abundant anaerobic microflora.” The fact that this study was not randomized or placebo-controlled contributes to limitations of the findings.

The researchers concluded that clindamycin as monotherapy may be a useful and safe alternative to combination clindamycin and rifampicin treatment but suggest that “[p]rospective randomized controlled trials are needed to confirm the results of this study.”

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Reference

Caposiena Caro RD, Cannizzaro MV, Botti E, et al. Clindamycin versus clindamycin plus rifampicin in hidradenitis suppurativa treatment: clinical and ultrasound observations [published online November 28, 2018]. J Am Acad Dermatol. doi: 10.1016/j.jaad.2018.11.035

December 31, 2018

Infection was the most common adverse medical condition across the 4 cohorts.

In patients with psoriasis, the use of biologic therapies compared with conventional systemic therapies (CST)/topical therapies is associated with a similar or lower risk for developing adverse medical conditions, according to study results published in the Journal of Drugs in Dermatology.

In this retrospective cohort study, data from a large US administrative claims database were used to explore the real-world risk for development of adverse medical conditions in adult patients with psoriasis treated with CST/topical therapies vs patients treated with biologic agents. Participants were classified into cohorts based on the treatment initiated on the index date: adalimumab, etanercept, infliximab, ustekinumab, or CST/topical therapies. Incident adverse medical conditions identified while on treatment from diagnoses recorded in medical claims included infections, malignancies (skin and nonskin), respiratory disease, mental disorders, and abnormal test results.

The following assessments were made: adverse medical condition risk with adalimumab, etanercept, and ustekinumab separately vs CST/topical therapies and adverse medical condition risk with adalimumab vs other biologic agents (etanercept, infliximab, and ustekinumab combined).

A total of 42,981 patients were identified (adalimumab: n=5197; etanercept: n=3311; infliximab: n=187; ustekinumab: n=1370; CST/topical therapies: n=32,916). Across the various cohorts, 46.2% to 53.1% of the participants were women, median age was 46 to 50, and the median duration of follow-up was 3.3 to 7.9 months.

Infection was the most commonly reported adverse medical condition in all cohorts (28.7% to 41.8% of patients). Adalimumab, etanercept, and ustekinumab were all associated with a significantly lower risk for infection compared with CST/topical therapies (adjusted hazard ratio [aHR] 0.93, 0.92, and 0.86, respectively; P <.05 for all).

Moreover, treatment with adalimumab was associated with a significantly lower risk for malignancies (aHR 0.71; P <.05) and treatment with etanercept was associated with a significantly lower risk for respiratory disease (aHR 0.80; P <.05). When adalimumab was compared with other biologic agents, a similar safety profile was reported with respect to the adverse medical conditions that were evaluated.

The investigators concluded that additional studies with longer follow-up periods are warranted in order to capture the long-term effect of psoriasis therapies on an individual’s risk for adverse medical conditions.

Disclosures: Design, study conduct, and financial support for the study were provided by AbbVie; AbbVie participated in the interpretation of the data, review, and approval of the manuscript. Multiple authors disclosed affiliations with pharmaceutical companies. See the reference for complete disclosure information.

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Reference

Wu JJ, Armstrong A, Singh R, et al. Adverse medical conditions across treatment options in patients with psoriasis: a claims-based analysis. J Drugs Dermatol. 2018;17(11):1211-1218.

December 31, 2018

Generic topical dermatologic drugs had a median percentage price decrease of 5.3% but a mean percentage price increase of 85.1% from 2013 to 2016.

Policies that generate increased market competition between topical dermatologic generic agents with a limited number of manufacturers may, in turn, lead to long-term price reductions. The negative association between the change in drug prices and the median number of manufacturers of these topical generic agents signifies a role for market competition in controlling costs within the dermatology armamentarium, according to the results of a retrospective cost analysis published in JAMA Dermatology.

The investigators sought to describe the association between changes in drug prices and the number of US Food and Drug Administration (FDA)-approved manufacturers among the most frequently used generic topical dermatologic products. They used cumulative annual claims data from the Medicare Part D Prescriber Public User File to identify 597 drugs prescribed by dermatologists with >10 claims. The FDA Orange Book was used to determine the number of manufacturers. The National Average Drug Acquisition Cost (NADAC) database provided the price per unit of each product.

Data were collected between 2013 and 2016. Drugs that were not topically administered, were non-dermatologic, were missing NADAC data, were lacking a generic formulation, or had <400 claims were excluded from the study. The primary study outcomes were the per-unit drug price and the number of FDA-approved manufacturers. Pricing measures, adjusted for inflation, were reported in 2016 US dollars.

A total of 116 topical dermatologic generic products comprised the current analysis, which represented 70.5% of the total Medicare Part D dermatologist-coded claims from calendar year 2015. Whereas drug formulations with 1 or 2 manufacturers during the study period maintained a median percentage price increase of 12.7%, those with  >6 manufacturers exhibited a median percentage decrease in price of 20.5%.

Moreover, products with 1 to 2 manufacturers had a 20.6%, 19.5%, and 33.2% higher percentage increase in price compared with those formulations with 3 to 4 manufacturers, 5 to 6 manufacturers, and >6 manufacturers, respectively. A statistically significant inverse relationship was reported between the percentage change in drug price and the median number of manufacturers (P =.005).

The investigators concluded that the findings from this study support policies that facilitate robust market competition among topical dermatologic generic agents produced by a small number of manufacturers, which may help pave the way for long-term price reductions.

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Reference

Li DG, Joyce C, Mostaghimi A. Association between market competition and prices of generic topical dermatology drugs. JAMA Dermatol. 2018;154(12)1441-1446.

December 28, 2018

Patients with moderate to severe plaque psoriasis typically require long-term treatment to achieve disease control.

According to study results published in the Journal of the European Academy of Dermatology and Venereology, long-term treatment with ixekizumab is not associated with any new safety signals and should be considered acceptably safe and tolerable for the treatment of moderate to severe plaque psoriasis.

Previous studies have shown ixekizumab to be effective with no unexpected safety signals to treat chronic psoriasis in a short-term treatment period up to 24 weeks. The investigators of this study sought to evaluate the long-term safety and tolerability of ixekizumab for treating patients with moderate to severe plaque psoriasis for up to 3 years.

The present analysis reported the cumulative safety data on up to 319 weeks of ixekizumab exposure in a cohort of 5689 adults with moderate to severe psoriasis recruited from 11 clinical studies. The primary outcomes were treatment-emergent adverse events, including serious infections, oral candidiasis, major adverse cerebrocardiovascular events, non-melanoma skin cancer, malignancies, and inflammatory bowel disease. Adjusting for exposure period, the investigators reported the incidence rates (IR) per 100 patient-years; frequencies and exposure-adjusted incidence rates were summarized by 12-week intervals through 156 weeks (3 years).

Of the 5689 participants, 3787 received ixekizumab treatment for at least 1 year, 3162 for at least 2 years, and 1659 for at least 3 years. The participants accounted for 12,061.5 patient years of overall ixekizumab exposure. Over 156 weeks, a total of 4775 (83.9%) patients reported treatment-related adverse events. The most commonly reported adverse events were similar to previous reports of short-term exposure, including infections (28.7 IR; 95% CI, 27.8-29.7), injection-site reactions (7.0 IR; 95% CI, 6.5-7.5), and allergic reactions/hypersensitivities (6.1 IR; 95% CI, 5.6-6.5).

The incidence rate of opportunistic infections was 1.8 (95% CI, 1.6-2.1), the most common being mucocutaneous candidiasis, with an incidence rate of oral Candida infection of 0.9 (95% CI, 0.8-1.1). The frequency and incidence rates of adverse events did not increase over time with longer ixekizumab exposure, nor did the investigators identify a trend of increasing incidence rates for adverse events of special interest over the study period. Serious adverse events were reported in 11.8% of patients, causing 6.7% of patients to discontinue treatment; death occurred in 23 (0.4%) patients.

As patients with moderate to severe plaque psoriasis typically require long-term treatment to achieve disease control, researchers concluded that ixekizumab had an acceptable long-term safety profile consistent with previously reported short-term safety data in treating this patient population.

Disclosures: This study was sponsored by Eli Lilly and Company.

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Reference

Langley RG, Kimball AB, Nakagawa H, et al. Long-term safety profile of ixekizumab in patients with moderate-to-severe plaque psoriasis: an integrated analysis from 11 clinical trials [published online September 10, 2018]. J Eur Acad Dermatol Venereol. doi:10.1111/jdv.15242

December 28, 2018

It is unclear whether the positive skin changes are a result of the combination therapy or microneedling alone.

Using a multi-ingredient antiaging facial moisturizer before and after radiofrequency microneedling is associated with significant improvements in skin attributes, such as radiance, tone, and smoothness, according to study results published in the Journal of Cosmetic Dermatology.

Researchers assessed the safety, tolerability, and efficacy of the multi‐ingredient antiaging face moisturizer (DEJ face cream®) in an open-label clinical study. They evaluated women who used the moisturizer for 2 weeks, received a radiofrequency microneedling procedure, and then used the moisturizer again for another 4 weeks. Clinical evaluations using the Glogau Wrinkle Scale, full‐face global skin attributes, and tolerability assessments were performed at each visit, and patient evaluations were completed at the final visit to assess procedure satisfaction. Data and pictures were collected at baseline, week 2, week 4, and week 6.

Of the 15 study participants, the average age was 51, with a Fitzpatrick skin type I-IV and mild to moderate wrinkles. The median Glogau score improved most significantly from week 4 to week 6 (P =.0293 between baseline and week 6). In skin attribute changes from baseline to week 6, 80% of the participants saw a 4-fold improvement in radiance (overall improvement in radiance P =.0005); 73% saw a 12-fold improvement in tone (overall improvement in tone P =.001); 87% saw a 7-fold improvement in skin visual smoothness (overall improvement in skin visual smoothness P =.0002); 87% saw a 7-fold improvement in skin texture (overall improvement in skin texture P =.0002); 73% saw a 4-fold improvement in redness (overall improvement in redness P =.0195); and 27% of patients achieved the best score associated with dryness at visit 4 compared with none and visit 1 (P =.0024). In all, 67% of patients saw a 6-fold improvement in overall appearance (overall improvement in appearance P =.0020).

After radiofrequency microneedling, erythema and edema increased significantly (P =.0002 and P =.0313, respectively), and while edema was completely resolved by week 4, one patient still had erythema at week 6. At the last visit, patient evaluation scores improved the most in overall improvement, brightness, texture, pigmentation, redness, and tightness, and 60% would recommend this procedure to family and friends. 

Future studies should incorporate a placebo or control arm and evaluate if radiofrequency microneedling is effective on its own or if the multi‐ingredient antiaging face moisturizer combination is necessary.

“It is unclear at this point whether the contribution of efficacy parameters is due to RF microneedling in combination with this multi-ingredient antiaging moisturizer or due to RF microneedling alone,” the authors said, noting that this would need to be the subject of future research.

Disclosure: This study was sponsored by Revision Skincare.

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Reference

Zahr AS, Kononov T, Sensing W, Biron JA, Gold MH. An open-label, single-site study to evaluate the tolerability, safety, and efficacy of using a novel facial moisturizer for preparation and accelerated healing pre and post a single full-face radiofrequency microneedling treatment [published online November 19, 2018]. J Cosmet Dermatol. doi: 10.1111/jocd.12817

December 26, 2018

Approval of the new indication was supported by data from KEYNOTE-017 trial which included 50 patients.

The Food and Drug Administration has granted accelerated approval to Keytruda (pembrolizumab; Merck) for the treatment of patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). The accelerated approval was based on tumor response rate and durability of response; continued approval for this indication may be contingent upon verification of clinical benefit in the confirmatory trials. 

Approval of the new indication was supported by data from KEYNOTE-017 (NCT02267603), a multlicenter, non-randomized, open-label trial (N=50) of patients with recurrent locally advanced or metastatic MCC who had not received prior systemic therapy for their advanced disease. 

The major efficacy outcome measures were overall response rate (ORR) and response duration assessed by blinded independent central review per RECIST 1.1. 

The ORR was 56% (95% CI, 41, 70) of which 24% were complete response. Of the responders (n=28), 96% had a response duration lasting >6 months, and 54% had a response lasting >12 months. At the time of analysis, the median response duration was not reached. 

Fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain were the most common adverse reactions associated with Keytruda monotherapy. 

Keytruda, a human programmed death receptor-1 (PD-1) blocking antibody, is already approved to treat various colorectal, gynecologic, head and neck, lymphoma, skin, and respiratory cancers. It is available as 50mg/vial as a lyophilized powder for IV infusion, and as a 25mg/mL per vial solution fo IV infusion.

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For more information call (800) 672-6372 or visit Keytruda.com.