Breakthroughs in Psoriasis and PsA Therapies: Bimekizumab, Upadacitinib and Deucravacitinib
VIDEO Highlight:Breakthroughs in Psoriasis and PsA Therapies: Bimekizumab, Upadacitinib - YouTube
Despite the recent explosion of new biologic treatments for psoriasis and PsA, there remains an unmet need for patients who do not have treatment success on these medications or who prefer a safe, effective oral treatment. During this session, April Armstrong, M.D., MPH reviewed three new treatment options to help fill these needs. Deucravacitinib, a TYK-2 inhibitor, was recently approved as a once daily oral treatment for adults with psoriasis. Tyrosine kinase-2 is a key mediator of psoriasis that signals through the IL-23/IL-17 pathway. Deucravacitinib is an allosteric inhibitor of the TYK-2 regulatory domain, minimizing the cross-inhibition of other members of the janus kinase family. In phase 3 studies comparing deucravacitinib 6 mg daily with apremilast 30 mg BID, up to 53.6% of deucravacitinib subjects achieved clear or almost clear skin at week 16 compared to 34.3% of apremilast subjects. Deucravacitinib displays durability of response, with PASI 75 rates being maintained through 112 weeks in long term extension studies. Treatment with deucravacitinib was well-tolerated with no serious infections leading to discontinuation and no relevant lab abnormalities seen.
Moving on to PsA, Dr. Armstrong introduced upadacitinib 15 mg once daily for patients with PSA who have had an inadequate response to TNF inhibitors. In phase 3 trials, 57% of patients treated with upadacitinib, a JAK-1 inhibitor, achieved ACR 20 at week 12 compared to 24% of those treated with placebo. Upadacitinib also led to statistically significant radiographic inhibition of PSA at week 24. Dr. Armstrong wrapped up this session with a review of bimekizumab, a dual IL-17A/F inhibitor currently under investigation for psoriasis and PSA. Bimekizumab shows rapid and robust clearance, with PASI 90 rates of 45.3% at week 4 and 90.8% at week 16. Ninety percent of patients who achieved a BSA of <1% at week 16 with bimekizumab were able to maintain that level of clearance through 3 years. Bimekizumab also shows promise for PSA, with 43.4% of patients achieving ACR 50 at week 16 compared to 6.8% of those on placebo. Oral candidiasis was the most common adverse event seen in clinical trials, with 16.4% of patients experiencing at least one episode during the first year of treatment.
Which Psoriasis Therapy for Which Patient
VIDEO Highlight: Which Psoriasis Therapy for Which Patient - YouTube
In the current era of psoriasis treatment clinicians have many agents to choose from, including oral small molecules, traditional immuno-suppressives such as methotrexate, and biologics of different classes. In this pearl-filled lecture, Mark Lebwohl, M.D. gave listeners many tips to help choose which medication should be given to which patient. Focusing on two common comorbidities, Dr. Lebwohl discussed the ideal treatments for patients with cardiac disease and malignancy.
Cohort studies have shown that at baseline, patients with severe psoriasis are at increased risk of myocardial infarction due to systemic inflammation. Treatment with TNF-a inhibitors has been associated with a decreased incidence of myocardial infarction compared to treatment with phototherapy or topical therapy. Similarly, unadjusted rates of major adverse cardiovascular events in patients treated with ustekinumab, an interleukin-12/23 inhibitor, were found to be lower than the rate of MACE in patients not on biologic therapy and similar to rates in those treated with TNF-a inhibitors. Additionally, treatment with IL-17 inhibitors, IL-12/23 inhibitors, and TNF-a inhibitors was associated with an overall decrease in non-calcified coronary plaque burden over one year compared to non-biologic treatment. Further studies are needed for IL-23 inhibitors.
Moving on to patients with a history of or active malignancy, Dr. Lebwohl recommends avoiding TNF-a inhibitors in this population. Systematic reviews have found increased incidence of non-melanoma skin cancer, malignant melanoma, and lymphoma in those treated with TNF-a inhibitors. Interestingly, non-clinical studies have implicated the IL-23 pathway in the promotion of tumor growth, and Dr. Lebwohl brought up the possibility of IL-23 and IL-17 inhibitors being protective against cancer. There have been no reports of increased malignancy rates for secukinumab, an IL-17 inhibitor, and no IL-17 inhibitor has malignancy as a contraindication in its package insert. To conclude, Dr. Lebwohl cautioned against the use of janus kinase inhibitors, methotrexate, and cyclosporine in patients with a history of malignancy as all three have been associated with increased risk of malignancy. Apremilast, an oral phosphodiesterase-4 inhibitor, appears to be safe and has no contraindication for malignancy, although one case report has been published of recurrent melanoma after starting apremilast.
What’s New and Hot in Photoprotection
VIDEO Highlight: What's New and Hot in Photoprotection - YouTube
Photoprotection is a critical component of maintaining healthy skin and preventing cutaneous malignancies. During this session, Roger I. Ceilley, M.D. reviewed the latest updates in photoprotection. Under ideal conditions, increasing SPF level from 50 to 100 only translates to a 1% increase in UVB protection. However, a recent split-face study of SPF 50 versus SPF 100 showed that faces treated with SPF 50 were 11x more likely to burn than the SPF 100 side, likely due to the sunscreens being applied at lower than recommended densities. Clinicians should realize that patients often do not apply the recommended amounts of sunscreen, and therefore should encourage patients to wear sunscreens labeled with a higher SPF.
Dr. Ceilley presented multiple studies implicating the role of long-wavelength UVA (>370 nm) and visible light in photoaging, photocarcinogenesis, and the development of pigmentary disorders. Unfortunately, there is a paucity of FDA-approved filters that block long-UVA wavelengths and none that block visible light. Sunscreen additives such as antioxidants and photolyases could offer protection from these wavelengths, but more rigorous testing is needed. Tinted sunscreens, which contain iron oxides and pigmentary titanium dioxides have been shown to reduce visible light transmission by 90% and should be recommended to patients with UV and visible light-induced pigmentary disorders.
Dr. Ceilley quickly reviewed current misconceptions and gaps in knowledge regarding sun protection in skin of color patients before transitioning to a discussion on environmental effects of photoprotection. Oxybenzone, a broad-spectrum UVB/UVA filter, is widely used in sunscreens due to its low cost and high cosmetic acceptability. Unfortunately, this workhorse filter has become a target of those concerned about the possible negative effects of oxybenzone on the environment, despite the fact that experiments showing these deleterious effects are not representative of real-world conditions. Dr. Ceilley encouraged dermatologists to be aware of the possible effects, but continue to recommend broad-spectrum sunscreens that patients will use consistently. Dr. Ceilley concluded this session with a few words on the use of polypodium leucotomos and nicotinamide for chemoprevention and a recently published study showing that sunscreen users do not have elevated levels of blood benzene levels compared to nonusers.
Saturday AM POTD: Efficacy and tolerability of roflumilast cream 0.3% in patients with chronic plaque psoriasis involvement on the face, intertriginous, or genital areas: Pooled Results from Phase 3 Trials (DERMIS-1 and DERMIS-2)
Roflumilast cream 0.3% is a selective and high potent phosphodiesterase 4 inhibitor recently approved for chronic plaque psoriasis in adolescents and adults. This poster presents data from two Phase 3, randomized, double-blind, vehicle-controlled trials of once-daily roflumilast cream 0.3% in patients with psoriasis, with subgroup analyses for special sites, defined as the face, intertriginous, or genital areas. For patients with any special site involvement, 41.7% of roflumilast-treated patients achieved IGA success at Week 8 compared with just 1.3% of vehicle-treated patients. Local tolerability was highly favorable with close to 98% of patients have no evidence of irritation at Week 8 on investigator-rated assessments. Roflumilast cream 0.3% was shown to be effective in special site areas with excellent tolerability.
What’s New and Hot in Medical Dermatology
VIDEO Highlight: What's New and Hot in Medical Dermatology - YouTube
Today’s era of medical dermatology may prove to be defined by one single class of medication: janus kinase inhibitors. With recent approvals for atopic dermatitis, plaque psoriasis, alopecia areata, and vitiligo, keeping track of all of the various JAK inhibitors can be difficult. In this highly anticipated session, Bruce Strober, M.D., Ph.D. reviewed the latest data on all of the new JAK inhibitors pertinent to medical dermatologists. Dr. Strober began by discussing the family of janus kinase molecules and how the therapeutic profile of each JAK inhibitor varies based on its relative potency and binding domain.
Transitioning to review each individual medication, Dr. Strober introduced deucravacitinib, a novel, oral selective TYK-2 inhibitor recently approved for the treatment of plaque psoriasis. Deucravacitinib binds to the TYK-2 regulatory domain with high selectivity leading to less cross-inhibition of other JAK molecules. In a phase 3 study comparing deucravacitinib 6 mg daily with apremilast 30 mg BID, 58.7% of deucravacitinib subjects achieved PASI 75 at week 16 compared to 35.1% of apremilast subjects.
Moving on to JAK inhibitors for atopic dermatitis, Dr. Strober reviewed impressive efficacy data for oral agents upadacitinib and abrocitinib, as well as the topical JAK inhibitors, ruxolitinib and delgocitinib. Baricitinib, a selective JAK1/2 inhibitor, was recently approved for alopecia areata. In phase 3 trials, 35.2% of patients achieved the primary endpoint of SALT score <= 20 at the 4 mg dose of baricitinib compared with just 5.3% of patients in the placebo group at week 36 with similar efficacy seen for eyebrow and eyelash regrowth.
Dr. Strober introduced a novel JAK inhibitor, povorcitinib, currently under investigation for the treatment of hidradenitis suppurativa. This session concluded with a quick word on the efficacy of topical ruxolitinib 1.5% cream BID, recently approved for the treatment of nonsegmental vitiligo. In phase 3 trials, approximately 30% of patients achieved a 75% improvement in facial VASI scores compared to 7.5-12.5% of those in the placebo group.
What’s New and Hot in Managing Hidradenitis Suppurativa
VIDEO Highlight: What's New and Hot in Managing Hidradenitis Suppurativa - YouTube
In this session, Joslyn Kirby, M.D., M.D., MEd provided the audience with an update on best practices for treating hidradenitis suppurativa. Dr. Kirby began by discussing a few therapies currently under investigation for HS. Povorcitinib, a novel janus kinase inhibitor, shows promise at higher doses with 88% of patients treated with 90 mg povorcitinib achieving HiSCR success. Data for upadacitinib, a JAK-1 inhibitor approved for AD, also looks promising along with a novel JAK1/TYK2 molecule currently under investigation.
For patients with Hurley Stage 3 disease, Dr. Kirby finds a combination of medical and surgical treatments to be most effective. Surgical deroofing can be a great adjunct for those on chronic medical therapy with a few persistent lesions. Biologic medications are also under investigation for hidradenitis suppurative. Treatment with secukinumab, an IL-17 inhibitor, led to up to 46.1% of patients achieving HiSCR in phase 3 studies, while bimekizumab, a novel IL-17A/F inhibitor, showed similar efficacy to adalimumab in one study.
For mild-to-moderate HS, Dr. Kirby encouraged the audience to use TNF-a inhibitors or IL-17 inhibitors, and highlighted that a combination of spironolactone and metformin can be effective in women with HS. Laser hair removal and punch deroofing can also be effective in those with mild HS. While hidradenitis suppurativa treatment can be difficult at times, Dr. Kirby used the conclusion of this session to remind the audience why there is hope for the future of HS!
Diagnostic and Therapeutic Approach to Idiopathic Pruritus
VIDEO Highlight: Diagnostic and Therapeutic Approach to Idiopathic Pruritus - YouTube
Pruritus is one of the most common complaints in dermatology but can often leave clinicians frustrated and puzzled. In this session, Tejesh Patel, M.D. provided tips on how to approach patients with chronic pruritus when they are encountered in clinic. After a brief review of epidemiology and itch pathogenesis, Dr. Patel emphasized the importance of taking a thorough history when evaluating the itchy patient. Duration of itch is critical to determine, as those who have been itchy for less than one year are more likely to have an occult malignancy than those who have been itchy for >1 year. Other risk factors for occult malignancy include male sex, age greater than 60 years, and history of liver disease and tobacco use.
Dr. Patel then discussed key features of an appropriate physical exam, including determining if skin lesions are primary or secondary, and if dermatographism is present. A basic work-up can include complete blood count with differential, complete metabolic panel, and thyroid function studies. Additional diagnostic work-up can be pursued based on history and physical exam findings. Initial empiric therapy for generalized pruritus can include bland emollients, topical corticosteroids, and anti-histamines if urticaria is present. Phototherapy can be effective but is often not practice for many patients. Dupilumab, a monoclonal antibody targeting IL-4 and IL-13 signaling, has been shown to be effective for prurigo nodularis and was recently approved for this indication. Case studies also support the efficacy of dupilumab for chronic pruritus of unknown origin. Other treatment options for chronic pruritus include gabapentinoids and anti-depressants. Janus kinase inhibitors also show impressive efficacy for reducing itch in psoriasis and atopic dermatitis patients.
Dr. Patel concluded this session with a brief overview of new therapeutics under investigation for chronic pruritus. Treatment with nemolizumab, an anti-IL-31 receptor antibody, led to a 53% reduction in peak pruritus scores at week 4 in patients with prurigo nodularis versus 20.2% in the placebo group. Nalbuphine, an oral kappa-opioid agonist and mu-opioid antagonist also shows promise for the treatment of prurigo nodularis with studies ongoing.
What’s New and Hot in Skin of Color Management
VIDEO Highlight: What's New and Hot in Skin of Color Management - YouTube
Melasma and other pigmentary disorders are common reasons for patients with skin of color to present to a dermatologist. In this session, Andrew F. Alexis, M.D., MPH provided the audience with important updates on the management of melasma. Topical treatment with triple therapy is the backbone of melasma treatment, but should often be combined with procedural therapies such as chemical peels, lasers, microneedling, or intradermal tranexamic acid to be most effective. Recent studies have shown topical stabilized cysteamine to be effective for melasma as well.
Dr. Alexis reminded the audience that glycolic acid, salicylic acid, and Jessner’s peels are generally safe in skin of color patients. Oral tranexamic acid 250 mg BID for 3 months plus photoprotection led to a 49% reduction in melasma severity scores compared to 18% reduction in the placebo group in one study. Patients should be screened for thromboembolic risks prior to use of TXA. All patients with melasma should be using rigorous photoprotection, and recent evidence has implicated long UVA and visible light wavelengths in the development of melasma. Use of tinted sunscreens with iron oxides that block visible light led to significantly greater reduction in melasma severity scores than sunscreens without iron oxide in studies. Adjunctive use of oral polypodium leucotomos supplementation with topical hydroquinone was shown to be superior to topical hydroquinone alone.
Transitioning away from melasma to another pigmentary disorder, Dr. Alexis reviewed data on topical ruxolitinib 1.5% cream for the treatment of nonsegmental vitiligo. At week 24, a significantly greater proportion of patients treated with ruxolitinib cream twice daily achieved a 75% improvement in facial vitiligo severity scores than placebo. Combination treatment with narrowband UVB therapy and ruxolitinib cream led to a higher proportion of patients achieving treatment success than with ruxolitinib alone. Dr. Alexis stressed the importance of recognizing rapidly progressive vitiligo, which is a dermatologic emergency. Oral mini-pulse dosing of dexamethasone 4 mg two days per week was shown to be efficacious in halting the spread of vitiligo for these patients.
Saturday PM POTD: Calcipotriene (CAL) and betamethasone dipropionate (BDP) cream demonstrates high efficacy and convenience in skin of color patients with plaque psoriasis.
Calcipotriene 0.005%-betamethasone dipropionate 0.064% (CAL/BDP) is an effective medication for psoriasis and was recently approved in a novel cream formulation. This poster presents a subgroup analysis from pivotal Phase 3 trials on the efficacy and tolerability of once-daily CAL/BDP cream versus CAL/BDP topical suspension and vehicle in skin of color patients with plaque psoriasis. At week 8, the proportion of patients with Fitzpatrick IV-VI skin achieving Physician Global Assessment (PGA) success in the CAL/BDP cream group (37.4%) was similar to the overall study population (38.7%) and significantly higher than the CAL/BDP topical suspension and vehicle groups. Skin of color patients scored the CAL/BDP cream similarly or higher than the total trial population on the psoriasis treatment convenience score.