Table of Content

Current Issue

Spring/Summer 2025, Vol. 32 No. 1

Hong Kong J. Dermatol. Venereol. (2025) 32, 78-80


Reports on Scientific Meetings

EADV Congress 2024

Reported by FPM Lau 劉沛雯, WH Chan 陳惠康

Date:   25-28 September 2024
Venue:   Amsterdam
Organiser:   European Academy of Dermatology and Venereology

Biologics and JAK inhibitors

Speaker: Jonathan I. Silverberg
Department of Dermatology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA

Atopic dermatitis is a chronic relapsing and remitting disorder. Shared decision-making approach should be employed and includes basic management, prescription topical therapy as well as systemic or phototherapy.

In this lecture, the speaker looked into various biologics and oral JAK inhibitors (JAKi) in the treatment of atopic dermatitis. Currently, Dupilumab, Lebrikizumab and Tralokinumab are approved in the US as 1st line treatment for atopic dermatitis (AD), after inadequate response or contraindication to topicals. For oral JAK inhibitors, Abrocitinib and Upadacitinib are approved as 2nd line treatment. Baracitinib is not approved in the US but is approved in the Europe as well as in Hong Kong for treatment of atopic dermatitis.

There had been studies that looked at the comparative efficacy between biologics and oral JAK inhibitors. In the HEADS-UP trial, comparison was made between Upadacitinib 30 mg vs Dupilumab 300 mg in combination with topical corticosteroids (TCS) in the treatment of adults with moderate to severe atopic dermatitis. Upadacitinib 30 mg has a quicker onset of action but response to Dupilumab do catch up to that of Upadacitinib on moderate end points by week 24. However, at more robust endpoint EASI 100, Dupilumab does not ‘catch up' to Upadacitinib (16% on Dupilumab vs 34% on Upadacitinib) but switching to or adding Upadacitinib from Dupilumab was associated with a substantial increase in efficacy.

In the JADE DARE trial, Abrocitinib 200 mg was compared against Dupilumab 300 mg in combination with TCS in adults with moderate to severe AD. Analysis of 11 patients with EASI >=16 or PP-NRS >=7 after 26 weeks of Dupilumab in JADE DARE switching to Abrocitinib 200mg + TCS in JADE EXTEND, Abrocitinib was found effective in patients who previously had inadequate response to Dupilumab. 8/11 (72%) had some improvement from baseline but were still classified as non-responders. At 12 weeks after switching to Abrocitinib and TCS, 10/11 (91%) had improved EASI scores with 10/11 of patients having EASI scores <16. Improvement was noted in 9/11 (82%) patients as early as 2 weeks after the switch.

Regarding safety data, common side effects of Dupilumab include ocular side effects as well as facial erythema and dermatitis. There are also rare occurrences of arthralgia, cold sores, psoriasis, worsening of cutaneous T-cell lymphoma (CTCL) as well as flaring of Th1/Th17 mediated immune comorbidities. Tralokinumab and Lebirkiuzmab have similar side effect profiles as Dupilumab but Tralokinomab possibly has less frequent or severe ocular surface disease or facial erythema.

For JAK inhibitors, acne is common in Updatactinib, whereas nausea and headache are common in Abrocitinib. Herpes zoster is common in both drugs and vaccination is recommended before commencement of medication. Laboratory monitoring for JAK inhibitors is needed to look out for thrombocytopenia, lymphopenia, neutropenia, anaemia, abnormal lipid and liver enzymes as well as Creatine Kinase (CK) elevations and there are black box warnings for serious infections, malignancy, mortality, MACE and thrombosis.

In the atopic dermatitis trials, the overall herpes zoster incidence was relatively low for Baricitinib, Abrocitinib and Upadactinib - around 2-4 per 100 patient years, comparable with other indications. However, it should be highlighted that the studies excluded patients with disseminated herpes zoester, disseminated herpes simplex, recurrent localised herpes zoster and those with history of eczema herpeticum. Hence the rate of herpes zoster would be expected to be higher if such patients are treated with JAK inhibitors. Recombinant zoster vaccine may be administered while on JAKi but the safety and vaccine efficacy is unknown. Live attenuated zoster vaccine on the other hand is contraindicated and should be administered 4 weeks prior to starting JAKi.

In terms of choice for treatment, it is essential to engage the patient, identify patient’s goals for disease management and together work as a team to arrive at a decision that best suits the patient. In general, biologics can achieve very good clinical responses with most patients getting at least partial response on signs and symptoms. It has few relative contraindications, has no drug-drug interactions, and are generally preferred as first line agents. When compared with JAKi, no laboratory monitoring and zoster vaccination are needed for biologics. Biologics may also be helpful in patients with other atopic comorbidities including asthma, eosinophilic esophagitis and nasal polyposis. Of note, Dupilumab is the only approved option for paediatric age group down to the age of 6 months and it is possible to taper Dupilumab to Q3 weeks or even Q4 weeks dosing off label. Both Talokinumab and lebrikizumab can be maintained on Q4 weeks dosing, with lebrikizumab appearing to be as effective as Dupilumab in network meta- analysis.

JAK inhibitors work well in patients who has failed biologics or other systemic therapies and may be used as monotherapy. It is highly efficacious, especially at higher doses and is particularly effective on more robust endpoints e.g. EASI 90, IGA0/1 and NRS-itch 0/1. Since it is also highly effective for other immune mediated disorders, benefit may be seen if patient has other comorbidities including rheumatoid arthritis, ulcerative colitis, ankylosing spondyloarthropathy. It is useful in patients with atopic dermatitis overlapping psoriasis, or more psoriasiform presentation of atopic dermatitis. Anecdotally, it is also less likely to paradoxically worsen CTCL and psoriasis. It has a quick onset of effect and, as an oral drug, it allows for flexible dosing, including drug holidays and intermittent use. JAK inhibitors may be useful off label as first line when a rapid onset of action is required, has concomitant autoimmune comorbidities, severe exacerbation in particular seasons, or if the patient has a strong preference for oral agent e.g. true needle phobia, or if there are priori concerns about ocular adverse events. However, benefits of off label first line use of oral JAK inhibitors should always be weighed against the potential risks, in particularly the rare but serious adverse effects.

Learning points:

  • Biologics such as Dupilumab are effective first line treatment for atopic dermatitis. Oral JAK inhibitors are second line options that offers faster and more robust response.
  • Laboratory monitoring is needed for JAK inhibitors and in general, biologics have less systemic risks and side effects.
  • It is important to employ a shared decision-making approach and tailor to the patient’s needs and comorbidities.

A new approach to treating patients with pemphigus vulgaris

Speaker: Pascal Joly
French Reference Center for Auto Immune Blistering Diseases, Rouen University Hospital, INSERM 1234, Rouen, France

Pemphigus vulgaris (PV) is a rare but serious autoimmune disease that causes painful blisters on the epidermis and mucous membranes. It occurs when the immune system produces antibodies against desmoglein 3 (and sometimes desmoglein 1), which are proteins that help intercellular adhesion. When these proteins are attacked, the epidermal cells lose their adhesion, leading to blisters and erosions.

Traditionally, treatment for PV has involved high doses of corticosteroids and immunosuppressants like azathioprine or mycophenolate mofetil. While these treatments can be effective, they often come with significant side effects, such as infections, osteoporosis, and diabetes. The introduction of rituximab, a monoclonal antibody that targets and depletes CD20+ B cells, has changed the landscape of PV treatment. Rituximab offers a way to manage the disease while reducing the need for steroids, thereby reduce related side effects.

The Ritux 3 Trial, published in 2017, was a key study that established rituximab as a first-line treatment for moderate-to-severe PV. In this trial, patients who received rituximab along with a short course of prednisone experienced much higher rates of complete remission at 24 months (89%) compared to those who only received prednisone (34%). Furthermore, rituximab helped decrease long-term steroid use and reduced the frequency of relapses.

A new approach is emerging that focuses on identifying patients at high risk of relapse through biomarkers. This allows for a personalised treatment strategy that includes maintenance infusions of rituximab to help prevent relapses. From the Ritux 3 trial, researchers identified that there are two types of relapse:

Early Relapse: Approximately 20% of patients may experience a relapse even while on rituximab within the first 12 months of treatment. This raises the question of whether an additional infusion of rituximab at the 6-month mark could help those at high risk of relapse and prevent these 20% from experiencing a return of symptoms.

Late Relapse: Another 20% of patients may relapse later, between the 2nd and 7th year of treatment. This also raises the possibility of administering an additional rituximab infusion to prevent relapses during this time frame.

Researchers have identified early relapse predictors, which include:

A study conducted by Hebert et al examined whether patients in complete remission with at least one of these predictors would benefit from an additional rituximab infusion at 6 months. The results showed a significant reduction in relapse rates-from an expected 17-19% to only 2% - while treating just 39% of the patients.

Researchers are now investigating similar predictors for long-term relapse, specifically for the period between 24 months and 4 years after treatment. This ongoing research aims to refine treatment strategies further and improve outcomes for patients with pemphigus vulgaris.

Learning points:

  • There are indictors available for personalised treatment for maintenance infusion of Rituximab in patient with PV.
  • Long term indictor is still under investigation.