Efficacy and safety of TNF-α inhibitors in refractory primary complex aphthosis: a patient series and overview of the literature

Sand, Freja Lærke; Thomsen, Simon Francis

doi:10.3109/09546634.2013.800633

Cited by 25 publications

(9 citation statements)

References 23 publications

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“…This study shows a correlation of reduced bacterial diversity with pro‐inflammatory cytokines IFN‐γ, IL‐17A and IL‐1β. There was no statistically significant correlation with TNF‐α, the role of which has been long established in RAS (Sand & Thomsen, 2013) or IL‐6 shown to be elevated in saliva of LP patients in a recent meta‐analysis (Mozaffari, Sharifi, & Sadeghi, 2018). Future studies should extend analyses to other Th17‐activating cytokines and inflammatory cytokines implicated in immune conditions associated with oral mucosal disease such as IL‐21 (Geri et al., 2011) as well as effector cytokines known to modify the composition of mucosal microbiota such as IL‐22 (Korn et al., 2014).…”

Section: Discussionmentioning

confidence: 87%

Oral bacterial diversity is inversely correlated with mucosal inflammation

et al. 2020

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Objective We investigated the relationship amongst the oral mucosal bacterial community, clinical severity and inflammatory markers in the two most common immune‐mediated oral mucosal diseases, namely recurrent aphthous stomatitis (RAS) and oral lichen planus (LP). Methods Patients with RAS (n = 15) and LP (n = 18) and healthy controls (n = 13) were recruited using criteria to reduce the effect of factors that influence the microbiota structure independently of oral mucosal disease. Clinical severity was quantified using validated scoring methods. DNA was extracted from oral mucosal swabs for 16S rRNA gene high‐throughput sequencing. Salivary cytokines were measured using cytometric bead assays. Correlation studies were conducted amongst microbial diversity, clinical scores and cytokine concentrations. Results We observed a significant reduction of bacterial diversity in LP and RAS patients compared to controls (p = .021 and .044, respectively). Reduced bacterial diversity in LP and RAS correlated with increased clinical scores of the two conditions (⍴ = −0.551 to −0.714). A negative correlation was observed between microbial diversity and salivary interferon‐γ, interleukin‐17A and interleukin‐1β (⍴ = −0.325 to −0.449). Conclusions This study reports reduced oral microbial diversity in the context of increased mucosal inflammation and supports the role for microbial diversity as a marker or contributor to oral mucosal inflammatory disease activity and development.

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Section: Discussionmentioning

confidence: 87%

Oral bacterial diversity is inversely correlated with mucosal inflammation

et al. 2020

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“…The response rate to TNF‐alpha inhibitors was almost 90% in patients presenting with recurrent oral and/or genital aphthosis who were otherwise unresponsive or intolerant to recommended systemic therapy. We and others have previously published patient series and case reports demonstrating efficacy of TNF‐alpha inhibitors in patients with primary complex aphthosis, but the 26 patients in this study comprise the so far largest group of patients treated with TNF‐alpha inhibitors . TNF‐alpha has been found to trigger inflammation, clinical manifestations, and recurrence of aphthous stomatitis in patients with Behcet's disease, which may explain the high response rate of TNF‐alpha inhibitors in our patients with primary complex aphthosis .…”

Section: Discussionmentioning

confidence: 87%

“…A positive treatment effect was defined for each disease as clearance or almost clearance of the mucocutaneous manifestations during at least 3 months of therapy. A subset of the patients described herein has been published previously .…”

Section: Methodsmentioning

confidence: 99%

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

Sand

Thomsen

2015

Dermatol Ther

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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.

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“…A case series evaluated the efficacy of adalimumab and etanercept for 18 patients with aphthous stomatitis (13 patients with recurrent oral and genital ulcers, and five patients with continuous aphthous ulcers). 120 Sixteen patients had complete to almost-complete clearance and two patients showed a partial response to treatment. Ten patients received adalimumab 40 mg twice monthly and eight received etanercept 50 mg once weekly.…”

Section: Resultsmentioning

confidence: 97%

Off-Label uses of Biologic Agents Approved for Psoriasis and Psoriatic Arthritis for Dermatological Conditions: Part II

Elbendary

Kellen

2017

Journal of Psoriasis and Psoriatic Arthritis

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Over the past decade or so, the treatment of patients with psoriasis has been revolutionized by the development of the biological agents, monoclonal antibodies that target specific aspects of the inflammatory cascades. The biologic agents approved by the Food and Drug Administration for psoriasis and psoriatic arthritis include adalimumab, etanercept, infliximab, ustekinumab, and secukinumab. The advantages of these agents are numerous: they are dosed less frequently than previously used systemic agents, they have a more favorable safety profile, and they have incredible efficacy, even in patients resistant to standard treatment. There are abundant reports of off-label uses of these drugs for other dermatological conditions and inflammatory dermatoses. This review highlights the ability of the biologic agents to treat a wide spectrum of dermatologic diseases.

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Efficacy and safety of TNF-α inhibitors in refractory primary complex aphthosis: a patient series and overview of the literature

Cited by 25 publications

References 23 publications

Oral bacterial diversity is inversely correlated with mucosal inflammation

Oral bacterial diversity is inversely correlated with mucosal inflammation

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

Off-Label uses of Biologic Agents Approved for Psoriasis and Psoriatic Arthritis for Dermatological Conditions: Part II

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