Off-label use of TNF-alpha inhibitors in a dermatological university department: retrospective evaluation of 118 patients

Abstract

Tumor necrosis factor-alpha (TNF)-alpha inhibitors are licensed for patients with severe refractory psoriasis and psoriatic arthritis. However, TNF-alpha inhibitors have also been used off-label for various recalcitrant mucocutaneous diseases. This study aimed to evaluate the efficacy and safety of TNF-alpha inhibitors used for off-label dermatological indications. We retrospectively evaluated patient records of 118 patients treated off-label with TNF-alpha inhibitors in a dermatological university department. Patients presented with severe aphthous stomatitis/genital aphthous lesions (26), chronic urticaria (25), hidradenitis suppurativa (29), acne conglobata (11), dissecting cellulitis of the scalp (two), orofacial granulomatosis (four), sarcoidosis (four), granuloma annulare (two), granulomatous rosacea (one), granuloma faciale (one), subcorneal pustulosis (one), pyoderma gangrenosum (four), Sweet's syndrome (four), Well's syndrome (one), benign familial pemphigus (one), lichen planus (one), and folliculitis decalvans (one). A significant number of these patients went into remission during therapy with TNF-alpha inhibitors. A total of 11 patients (9%) experienced severe adverse effects during therapy. Off-label therapy with TNF-alpha inhibitors may be considered for selected patients with severe recalcitrant mucocutaneous diseases. The risk of severe adverse effects signals that a thorough benefit-risk assessment should be performed before initiating off-label treatment with TNF-alpha inhibitors for these conditions.

Effectiveness and safety of omalizumab in chronic spontaneous or inducible urticaria: evaluation of 154 patients

“…Of all patients, 39·6% were previously treated with prednisolone and 26·0% had been treated with dapsone or one or more immunosuppressant drugs such as ciclosporin A, azathioprine, mycophenolate mofetil, methotrexate and/or tumour necrosis factor (TNF) inhibitors. We have previously reported that among a subset of 25 patients with chronic urticaria who were naïve to biological drugs or who had received omalizumab, 60% obtained complete or almost complete resolution of urticaria and angioedema after onset of therapy with either adalimumab or etanercept, whereas another 15% of patients experienced a partial response to treatment with these TNF inhibitors …”

“…We have previously reported that among a subset of 25 patients with chronic urticaria who were na€ ıve to biological drugs or who had received omalizumab, 60% obtained complete or almost complete resolution of urticaria and angioedema after onset of therapy with either adalimumab or etanercept, whereas another 15% of patients experienced a partial response to treatment with these TNF inhibitors. 2,3 The initial dose of omalizumab given was 150 mg every 2 weeks in 45Á5% of cases and 300 mg every 4 weeks in 55% of cases (Table 1). At the time of treatment, use of omalizumab for CSU was still off-label.…”

Cutaneous side effects of TNF‐alpha inhibitors

“…exazerbieren diese, bezeichnet man sie als "paradox": Plaque-Psoriasis, Psoriasis palmoplantaris pustulosa, Psoriasis pustulosa generalisata (Zumbusch), Akne inversa, Lupus erythematodes (kutane Form, drug-induced), Vaskulitiden, bullöse Dermatosen, Granuloma anulare, Lichen ruber planus, Alopecia areata, Vitiligo und Sarkoidose [ 8 ] . Treten die folgenden Dermatosen unter TNF α -Inhibition neu auf, bzw.…”

“…In Deutschland sind derzeit vier TNF α -Antikörper (Infl iximab, Adalimumab, Certolizumab, Golimumab) sowie das Rezeptorfusionsmolekül Etanercept zugelassen (Tabelle 1 ). Neben den Indikationen rheumatoide Arthritis, ankylosierende Spondylitis, Psoriasis, Psoriasis-Arthritis, Morbus Crohn, Colitis ulcerosa, Hidradenitis suppurativa und Uveitis gibt es Berichte über erfolgreiche experimentelle Anwendung im Off-Label-Use unter anderem bei Psoriasis pustulosa, subkornealer Pustulose, Pityriasis rubra pilaris, Morbus Behçet, Granuloma anulare, Granuloma anulare disseminatum, Pyoderma gangraenosum, und bullösen Autoimmundermatosen [ 7,8 ] .…”

Challenges in the management of pediatric blepharokeratoconjunctivis / ocular rosacea

“…• TNF-α inhibitors (e.g. Infliximab) have successfully been used off-label in adults for the treatment of granulomatous rosacea [29]. Cytokines, chemokines, and Toll-like receptors may become potential targets for future therapeutic interventions in rosacea and possibly BKC.…”