Behcet’s syndrome and hidradenitis suppurativa

Apremilast effective in Behcet's Syndrome

The oral phosphodiesterase (PDE)4 inhibitor apremilast displayed a significant effect on ulcers and ulcer pain associated with Behcet´s syndrome in the RELIEF trial [16]. Behcet's syndrome is a rare, chronic, multi-system inflammatory disorder characterised by oral and genital ulcers, skin lesions, uveitis, arthritis, with vascular, central nervous system, and gastrointestinal involvement.

A key symptom occurring in nearly all patients is painful recurrent oral ulcers that can be disabling and have a substantial effect on QoL: there are currently no effective treatment options for them. The oral PDE4 inhibitor apremilast modulates inflammatory mediators and has demonstrated efficacy in a Phase 2 Behcet's syndrome study. These preliminary data were the reason for a Phase 3 trial with apremilast.

In the RELIEF study, a total of 207 patients were randomised to apremilast (30 mg twice daily) or placebo. At Week 12, the area under the curve (AUC) for the number of oral ulcers had a statistically significant reduction in apremilast compared to placebo (129.5 vs. 222.1; P<0.0001). The AUC was chosen as the trial's primary endpoint because it assesses the change in the number of oral ulcers over time, accounting for the clinical characteristic of oral ulcers repeatedly remitting and recurring in Behcet's syndrome.

“Apremilast had also a significant effect on the ulcer pain and overall disease activity measures, and improved QoL of patients with Behcet's syndrome,” said Dr Yusuf Yazici of the New York University School of Medicine during the presentation of the data. QoL improved significantly in patients taking apremilast (P=0.0003).

The most common adverse events observed in the trial were diarrhoea (41.3% with apremilast, 19.4% for placebo), nausea (19.2% with apremilast, 10.7% for placebo), headache (14.4% for apremilast, 9.7% for placebo) and upper respiratory tract infections (11.5% for apremilast, 4.9% for placebo). The safety profile was consistent with the known safety profile of apremilast in studies with psoriasis patients.

First specific therapy for patients with hidradenitis suppurativa

An antibody against a split product of the complement system was safe and showed impressive clinical efficacy in an open-label Phase 2a study in patients with severe hidradenitis suppurativa [17].

C5a is a split product of complement that has been shown to be increased in hidradenitis suppurativa [18]. A high expression of C5a is also associated with the severity of the disease and stimulates overproduction of TNF-α and, therefore, may be a future therapeutic agent. IFX-1 is a humanised monoclonal IGG4K antibody that specifically binds to the soluble human complement split product C5A.

Twelve patients with hidratenitis suppurativa were treated with weekly infusions of 800 mg IFX-1 for eight weeks and followed up for another 12 weeks. IFX-1 was well-tolerated. “For us, it was important to see that the antibody blocks only the split product C5a, which is responsible for the inflammatory action, but not the fragment C5b, which is needed for host defence”, explained Prof. Evangelos Giamarellos-Bourboulis, of the National and Kapodistrian University of Athens Medical School in Greece, during the presentation of the data.

Although half of the participants experienced adverse events, these were not related to the drug but to the disease itself. The antibody displayed a remarkable efficacy (secondary endpoints): at the end of the treatment period on Day 50, 75% of patients showed a clinical response. This response was maintained and was even better at the end of the follow-up period, 84 days after the last treatment. At that time, 83% of participants were responder. Patients also improved according to the PGA.

In addition, there was a significant change of the abscess and nodule count, which was also maintained during the follow-up period. “We did also notice that the dimensions of the lesions diminished,” said Prof. Giamarellos-Bourboulis. C5 levels showed a complete blockade during the entire treatment period. Due to these results, a larger Phase 2 study is currently being planned to confirm these results.

16. Yazici, Y. Abstract 6703, AAD Annual Meeting, February 16–20 2018.
17. Giamarellos-Bourboulis, EJ. Abstract 6797, AAD Annual Meeting, February 16–20 2018.
18. Kanni, T. et al. Br J Dermatol 2018 Feb 6.



Posted on 20 December 201817 May 2024