Spesolimab, an anti-interleukin-36 receptor antibody, in patients with moderate-to-severe atopic dermatitis: Results from a multicentre, randomized, double-blind, placebo-controlled, phase IIa study.

BACKGROUND: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease, and there is increasing evidence that the interleukin (IL)-36 pathway may play a role in the pathogenesis of AD. OBJECTIVES: To evaluate the efficacy and safety of spesolimab, a novel anti-IL-36 receptor antibody, in adult patients with moderate-to-severe AD. METHODS: In this phase IIa study, 51 eligible patients were randomized 2:1 to receive intravenous doses of spesolimab 600 mg or placebo every 4 weeks. The primary endpoint was the percentage change from baseline in Eczema Area and Severity Index (EASI) score at Week 16. RESULTS: The decrease in EASI score from baseline to Week 16 was -37.9% for spesolimab versus -12.3% for placebo (adjusted mean difference -25.6%, p = 0.149). A predefined sensitivity analysis, excluding data from patients who used restricted corticosteroids, resulted in an adjusted mean difference of -48.3% (nominal p = 0.024). Spesolimab was well tolerated, with no clinically relevant safety signals. CONCLUSIONS: This is the first study to evaluate the IL-36 pathway inhibition in AD. Although not statistically significant, numerical improvements were observed in the primary endpoint of change from baseline in the EASI score. Spesolimab had an acceptable safety profile, with no unexcepted safety concerns.

Efficacy and Safety of Systemic Treatments for Skin and Joint Manifestations in Patients With Psoriasis.

Psoriasis is a chronic, systemic disease with features suggestive of autoimmune dysregulation. Patients with psoriasis vulgaris frequently experience systemic comorbidities, including cardiovascular and metabolic diseases, and approximately 30% develop psoriatic arthritis (PsA), which requires treatment. It is important that physicians and patients are aware of the breadth of treatment options available to treat the complete spectrum of psoriasis manifestations. This narrative review summarizes clinical information from approved systemic psoriasis therapies relevant to the treatment of PsA and related systemic pathologies. We include pivotal clinical trials of biologic therapies that are approved by the US Food and Drug Administration for psoriasis and PsA and additional studies identified from PubMed and congress abstract searches through August 21, 2019. We comment on the real-world effectiveness of traditional nonbiologic treatment options, including methotrexate, cyclosporine, acitretin, systemic corticosteroids, and nonsteroidal anti-inflammatory drugs and consider targeted synthetic and biologic disease-modifying antirheumatic drugs and their efficacy and safety in treating skin and joint manifestations. Finally, we discuss key considerations when managing patients with PsA as a comorbidity of psoriasis. The individual treatment needs of patients should be met while psoriasis and its systemic complications are managed. When addressing these needs, it is important to consider modern biologics and other systemic therapies. J Drugs Dermatol. 2020;19(3): doi:10.36849/JDD.2020.4690THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

T-cell-mediated immune response to pneumococcal conjugate vaccine (PCV-13) and tetanus toxoid vaccine in patients with moderate-to-severe psoriasis during tofacitinib treatment.

BACKGROUND: Psoriasis is often treated with immunomodulatory therapies that can affect the immune response to common antigens. Tofacitinib is an oral Janus kinase inhibitor. OBJECTIVE: To characterize the effect of long-term exposure to tofacitinib 10 mg twice daily on T-cell function in psoriasis patients. METHODS: Patients completing at least 3 months' continuous treatment with tofacitinib 10 mg twice daily were vaccinated with T-cell-dependent vaccines (monovalent tetanus toxoid and 13-valent pneumococcal conjugate [PCV-13]). Patients were assessed at baseline (before vaccination) and then again 4 weeks after vaccination. For PCV-13, we evaluated serotype-specific, opsonophagocytic antibody responses, and for tetanus toxoid, we evaluated humoral responses. RESULTS: Among 60 patients who completed the study, the geometric mean fold rise from baseline for the 13 PCV serotypes at 4 weeks postvaccination varied from 8.3 (serotype 3) to 101.9 (serotype 6A). Similar results were observed for patients with and without lymphopenia at baseline. For tetanus toxoid, 51 (88%) patients had ≥2-fold and 35 (60%) patients had ≥4-fold rise in antibody concentration. LIMITATIONS: There was no placebo control. CONCLUSION: Most psoriasis patients who receive tofacitinib can mount satisfactory T-cell-dependent responses to PCV-13 and tetanus vaccines.

Low-level laser/light therapy for androgenetic alopecia.

Androgenetic alopecia (AGA) is a persistent and pervasive condition that affects men worldwide. Some common treatment options for AGA include hair prosthetics, oral and topical medications, and surgical hair restoration (SHR). Pharmaceutical and SHR treatments are associated with limitations including adverse side effects and significant financial burden. Low-level laser or light (LLL) devices offer alternative treatment options that are not typically associated with adverse side effects or significant costs. There are clinic- and home-based LLL devices. One home-based laser comb device has set a standard for others; however, this device requires time devoted to carefully moving the comb through the hair to allow laser penetration to the scalp. A novel helmet-like LLL device for hair growth has proven effective in preliminary trials and allows for hands-free use. Regardless, there are few clinical trials that have been conducted regarding LLL devices for AGA and results are mixed. Further research is required to establish the true efficacy of these devices for hair growth in comparison to existing alternative therapies.

XdemvyTM (Lotilaner Ophthalmic Solution) 0.25% Topical Solution for the Treatment of Demodex Blepharitis.

XdemvyTM (lotilaner ophthalmic solution) 0.25% topical solution was recently approved for the treatment of Demodex blepharitis in adults aged ≥18 years. As an antiparasitic agent, lotilaner selectively inhibits gamma-aminobutyric acid chloride channels specific to the parasite and induces spastic paralysis, leading to death of Demodex blepharitis mites. In two randomized, double-masked, vehicle-controlled, multi-center, phase-3 clinical trials (Saturn-1 and Satuirn-2), lotilaner 0.25% topical solution was investigated for the treatment of Demodex blepharitis. Patients were assigned to receive either lotilaner 0.25% topical solution or vehicle (solution that did not contain lotilaner as an active ingredient) twice daily for 6 weeks. On day 43, lotilaner group demonstrated primary efficacy in achieving collarette cure ([collarette grade 0], Saturn-1: study group 44% [92/209], vehicle 7.4% [15/204]; Saturn-2: study group 56% [108/193], vehicle 12.5% [25/200]). Secondary efficacy was achieved by eradication of mite ([0 mite/lash], Saturn-1: study group 67.9% [142/209], vehicle 17.6% [36/304]; Saturn-2: study group 51.8% [99/193], vehicle 14.6% [29/200]), composite cure ([grade 0 collarette as well as grade 0 erythema], Saturn-1: study group 13.9% [29/209], vehicle 1.0% [2/204]; Saturn-2: study group 19.2% [37/193], vehicle 4% [8/200]), and erythema cure ([grade 0 erythema], study group 19.1% [40/209], vehicle 6.9% [14/204]; Saturn-2: study group 31.1% [60/193], vehicle 9.0% [18/199]). The adverse events were mild, with the most common being pain at instillation site. The recommended regimen for lotilaner 0.25% solution is one drop in each eye twice daily for 6 weeks.

Spevigo® (Spesolimab-Sbzo) Injection for the Treatment of Generalized Pustular Psoriasis.

Spevigo® (spesolimab-sbzo) injection was recently approved for the treatment of generalized pustular psoriasis (GPP) in adults aged 18- 75 years. Spesolimab, a monoclonal antibody, binds to the interleukin-36 (IL-36) receptor and prevents its activation by IL-36 cytokines, leading to reduced inflammation, skin lesions, and flares. In a randomized placebo-controlled, phase 2 study (Effisayil-1, NCT03782792), 53 patients were randomized to spesolimab (n = 35) and placebo (n = 18) to evaluate the effect of a one-time 900-mg dose of spesolimab versus placebo against GPP flares. The primary endpoint was Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 (no visible pustules) and the key secondary endpoint was the GPPGA total score of 0 or 1 (clear or almost clear skin) at the end of week 1. The primary endpoint was achieved by 54% (19/35) of patients in the spesolimab group and 6% (1/18) of patients in the placebo group. The key secondary endpoint was achieved by 43% (15/35) of patients in the spesolimab group and 11% (2/18) of patients in the placebo group. In the first week, adverse events (mild to severe) were reported in 66% (22/35) of patients in the spesolimab group and 56% (10/18) in the placebo group.

OtezlaTM (Apremilast 30-Mg Tablets).

OtezlaTM was first approved on March 21, 2014 for the treatment of psoriatic arthritis, on September 23, 2014 for moderate to severe plaque psoriasis and on July 19, 2019 for the treatment of oral ulcers associated with Behcet's disease (BD). Apremilast is an inhibitor of phosphodi-esterase-4, an enzyme involved in the pathogenesis of several dermatologic conditions. This review explores the potential utility of apremilast in the treatment of other unapproved dermatologic indications.

DAXXIFYTM (DaxibotulinumtoxinA-Lanm) for Injection, for Intramuscular Use.

DAXXIFYTM (daxibotulinumtoxinA-lanm) for intramuscular injection was recently approved for temporary improvement in the appearance of the moderate to severe glabellar lines (GLs) associated with corrugator and/or procerus muscle activity in adult patients. DaxibotulinumtoxinA for Injection (DAXI) includes a purified 150-kDA botulinum toxin Type A (BoNTA) formulated with a novel peptide excipient that is positively charged and helps to bind the neurotoxin to negatively charged neuronal membrane for a longer duration. The effectiveness of DAXI was evaluated in two phase 3 trials, SAKURA 1 and SAKURA 2, using a randomized, double-blind, placebo-controlled design. The primary endpoint (treatment success) was a composite clinical outcome (investigator and subjects) of ≥2-point improvement in severity of GLs at week 4. In SAKURA 1, the treatment success was 74% (148/201) in subjects treated with DAXI and 0% in subjects treated with placebo. In SAKURA 2, the treatment success was 74% (152/205) in subjects treated with DAXI and 0% in subjects treated with placebo. An open-label study, SAKURA 3, included 2,691 participants, who underwent three consecutive treatment cycles. These individuals were recruited from either SAKURA 1 or SAKURA 2 trials, or were new to the study and received DAXI. Treatment success proportions were 73.2%, 77.7%, and 79.6% across the three consecutive treatment cycles. The recommended dose is 40 units for the Glabellar-complex divided in traditional five intramuscular injections at five injection sites (medial and lateral corrugator bilaterally and one injection in the procerus muscle).

Libtayo® (Cemiplimab-rwlc) Injection for Intravenous Use.

Libtayo® (cemiplimab-rwlc) injection for intravenous use was recently approved by the US Food and Drug Administration (FDA) for locally advanced basal cell carcinoma (laBCC) and metastatic basal cell carcinoma (mBCC), both being the advanced stages of BCC. In the past, it was approved by the FDA for the treatment of metastatic cutaneous squamous cell carcinoma (mCSCC) and locally advanced cutaneous squamous cell carcinoma (laCSCC), both being the advanced stages of CSCC. Cemiplimab is a monoclonal antibody that works by blocking the programmed death-1 pathway. In two open-label, single-arm, phase 2 studies, cemiplimab was investigated for the treatment of advanced stages of BCC (study 1620, NCT03132636) and advanced stages of CSCC (study 1540, NCT02760498). The primary endpoint was objec-tive response rate (ORR) per independent central review. In the study 1620, both mBCC and laBCC received cemiplimab 350 mg every 3 weeks. ORR was 21% (6/28) and 31% (26/84) in the mBCC and laBCC groups, respectively. In the study 1520, mCSCC was divided into two groups: one receiving cemiplimab 350 mg every 3 weeks (Q3W) and another receiving 3-mg/kg cemiplimab every 2 weeks (Q2W); the third group, laCSCC, received cemiplimab 3 mg/kg every 2 weeks. ORR was 41% (23/56) in the Q3W group, 49% (29/59) in the Q2W group, and 44% (34/78) in the laCSCC group. An acceptable safety profile and antitumor activity was discovered in patients treated with cemiplimab. The recommended dosage for cemiplimab to treat advanced stages of BCC and CSCC is 350 mg every 3 weeks administered intravenously over 30 min.

OpzeluraTM (Ruxolitinib) Cream 1.5.

Ruxolitinib cream 1.5% was first approved by the US Food and Drug Administration (FDA) in 2011. Opzelura™ cream was introduced by Incyte Dermatology in 2021 for the short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis (AD) in non-immunocompromised patients aged ≥12 years, whose clinical manifestations are not controlled with prescribed topical therapies, such as topical corticosteroids, topical calcineurin inhibitors, or topical phosphodiesterase-4 ( PDE4) inhibitors, or when such therapies are not advisable. Ruxolitinib is a Janus kinase (JAK) inhibitor that addresses inflammation in AD. It selectively inhibits JAK1 and JAK2, blocking JAK and activating signal transducer and activator of transcription (STAT), thereby interrupting the cytokine pathways responsible for cutaneous inflammation. The targeted downstream cytokines include Interleukin- 4 (IL-4), IL-13, IL-31, and cytokine thymic stromal lymphopoietin (TSLP), which play pivotal roles in the itching and inflammation experienced by AD patients. Ruxolitinib cream is directly applied as a thin layer over AD lesions twice daily up to 20% body surface area (BSA) using no more than 60 g per week. It can be used for up to 8 weeks on delicate or thin skin surfaces.

A Review of the Risk of Cow's Milk Protein Allergy in Oral Medication.

Immunoglobulin E (IgE)-mediated cow's milk allergy (CMA) is a common food reaction resulting from the consumption of cow's milk protein (CMP). The clinical manifestations of CMA include mild to severe urticaria, skin-manifested hypersensitivity reactions, and anaphylaxis. Food allergies may affect 8% of children and 10% of adults. The Federal Food, Drug, and Cosmetic Act (FD&C Act) requires that the label of a food must declare the presence of a "major food allergen" (MFA) contained in the food or ingredient. The Food and Drug Administration (FDA) generally regards milk protein concentrate (MPC) as safe for human consumption and use. The increasing use of MPC in formulations raises the need for its revelation in prescription and on labels of over-the-counter drugs. This review investigates oral and topical (including mucosal) preparations containing MPC for dermatologic and other uses and their therapeutic impact. Our findings suggest that for the adult population, the risk of serious cow's milk protein allergy (CMPA) from medications is minimal.

SOTYKTUTM (Deucravacitinib 6-mg Tablets)- A New Agent for the Management of Adult Plaque Psoriasis.

SOTYKTUTM (deucravacitinib) is a newly approved oral agent for managing moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. Deucravacitinib is a highly selective allosteric tyrosine kinase 2 inhibitor targeting dysregulated cytokine responses in psoriasis patients. Its efficacy was demonstrated in two randomized, placebo- and active comparator-controlled phase 3 trials, where a significantly higher proportion of patients, up to 58.4% (194/332), achieved lessening of symptoms at week 16. The recommended dosing regimen of deucravacitinib is 6 mg once daily. More frequent adverse reactions occurring in the deucravacitinib-treated patients include upper respiratory infection (19.2% [161/840]), increase in blood creatine phosphokinase (2.7% [23/840]), herpes simplex infection (2.0% [17/840]), mouth ulcers (1.9% [16/840]), folliculitis (1.7% [14/840]), and acne (1.4% [12/840]). Continuance of treatment for up to week 52 did not increase the exposure-adjusted rates of adverse reactions. The selectivity and specificity of deucravacitinib treatment may improve its long-term safety profile, compared to other Janus kinase inhibitors.

YCANTHTM (Cantharidin) Topical Solution.

YCANTHTM (cantharidin) topical solution has been approved recently for the treatment of molluscum contagiosum (MC) in children (aged ≥2 years) and adults. It works by activating serine proteases that lead to blistering and inflammation, promoting shedding of infected cells and viral clearance. In two phase-3, randomized, double-blind, vehicle-controlled trials of similar design, VP-102 (a drug-device combination, containing cantharidin 0.7% w/v and inactive ingredients, such as gentian violet, acetone, and denatonium benzoate, administered with an applicator) was investigated for the treatment of MC. VP-102 and vehicle were applied topically once every 21 days until complete clearance of lesions was observed, or for up to four treatments. Cantharidin demonstrated efficacy in achieving the primary outcome, at day 84/visit 4 (Cantharidin Application in Molluscum Patients [CAMP-1], VP-102: 46% [73/160], vehicle: 18% [19/106]; and CAMP-2, VP-102: 54% [81/150], vehicle: 13% [15/112]). Common adverse events were mild to moderate, such as lesions at the site of application, pruritus, and pain. The recommended regimen of cantharidin topical solution is its application once every 21 days until complete clearance of lesions is observed, or up to four treatments.

ZORYVETM (Roflumilast) Cream: A Topical Phosphodiesterase-4 Inhibitor for the Treatment of Psoriasis.

ZORYVETM (roflumilast) cream is a topical phosphodiesterase-4 (PDE-4) inhibitor that has been recently approved for the treatment of plaque psoriasis. It is also indicated for use in intertriginous areas. Roflumilast, the active ingredient, inhibits PDE-4, leading to the suppression of pro-inflammatory immune responses in psoriatic lesions. Two phase 3 clinical trials have demonstrated the efficacy of once daily application of roflumilast to treat plaque psoriasis in patients aged 12 years and older. At week 8, an investigator's global assessment score of 0 or 1 with a grade 2 improvement from baseline, the primary efficacy end point, was observed in 39.1% (225/576) of patients applying roflumilast, compared to 6.6% (20/305) of patients applying vehicle. Common adverse events reported were diarrhea, headache, insomnia, nausea, pain at application site, upper respiratory tract infection, and urinary tract infection.

LITFULOTM (Ritlecitinib) Capsules: A Janus Kinase 3 Inhibitor for the Treatment of Severe Alopecia Areata.

LITFULOTM (ritlecitinib) capsules were recently approved for the treatment of severe alopecia areata in adolescents and adults, aged ≥12 years. Ritlecitinib is the active ingredient and a dual inhibitor of Janus kinase 3 and the tyrosine kinase expressed in hepatocellular carcinoma kinase family. It prevents immune attack on the hair follicles that leads to hair loss. In a phase 2b-3 dose-dependant study, five doses of oral ritlecitinib and placebo administered once daily (QD) were investigated. Ritlecitinib demonstrated efficacy in achieving the primary outcome, Severity of Alopecia Tool (SALT) score of ≤20, at week 24 (31% [38/124] 200-mg ritlecitinib QD for 4 weeks, then 50 mg QD for 20 weeks; 22% [27/121] 200-mg ritlecitinib QD for 4 weeks, then 30 mg QD for 20 weeks; 23% [29/124] 50-mg ritlecitinib QD; 14% [17/119] 30-mg ritlecitinib QD; 2% [1/59] 10-mg ritlecitinib QD; and 2% [2/130] placebo). Mild to moderate common adverse effects were observed, which included headache, nasopharyngitis, and upper respiratory tract infection. The recommended regimen of ritlecitinib capsules is 50 mg QD with without food and swallowed whole.

Epsolay™ (Microencapsulated Benzoyl Peroxide 5%) Cream for the Topical Treatment of Rosacea.

EpsolayTM cream is a novel topical treatment that utilizes microencapsulated benzoyl peroxide to treat moderate to severe papulopustular rosacea. It is effective at decreasing, and for some patients clearing, the papules, pustules, and telangiectasias associated with rosacea. It is well-tolerated with minimal adverse effects and has demonstrated efficacy comparable to other topical agents that are used for the condition.