Rituximab in practice: Clinical evaluation of patients with pemphigus after rituximab administration

Mahmoudi, Hamidreza; Tavakolpour, Soheil; Balighi, Kamran; Farid, Ali Salehi; Nili, Ali; Jan, Delnavaz; Daneshpazhooh, Maryam

doi:10.1111/dth.14633

Cited by 12 publications

(13 citation statements)

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“…Despite a rather low (12 of 46) relapse rate in the RTX group compared to the CS group (20/44), most of relapses (9/12) occurred quite early in the RTX group during the first 12 months after the start of treatment, whereas relapses in the CS group occurred more regularly during patients' follow-up (7 during the 1 st year and 13 during the 2 nd year after the start of treatment). A high relapse rate has been consistently reported in the literature in patients with pemphigus who received only one cycle of rituximab (11)(12)(13)(14), as well as in other auto-immune diseases. It has been hypothesized that some relapses after rituximab might be due to the increase of serum BAFF levels, which could promote the recovery of auto-reactive B cells (4,15).…”

Section: Introductionmentioning

confidence: 84%

Modifications of the BAFF/BAFF-Receptor Axis in Patients With Pemphigus Treated With Rituximab Versus Standard Corticosteroid Regimen

et al. 2021

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The efficacy of the B-cell-depleting agent rituximab has been reported in immune diseases but relapses are frequent, suggesting the need for repeated infusions. The B-cell activating factor (BAFF) is an important factor for B cell survival, class switch recombination and selection of autoreactive B cells, as well as maintaining long-lived plasma cells. It has been hypothesized that relapses after rituximab might be due to the increase of serum BAFF levels. From the Ritux3 trial, we showed that baseline serum BAFF levels were higher in pemphigus patients than in healthy donors (308 ± 13 pg/mL versus 252 ± 28 pg/mL, p=0.037) and in patients with early relapse compared who didn’t (368 ± 92 vs 297 ± 118 pg/mL, p=0.036). Rituximab and high doses of CS alone have different effects on the BAFF/BAFF-R axis. Rituximab led to an increase of BAFF levels associated to a decreased mRNA (Day 0: 12.3 ± 7.6 AU vs Month 36: 3.3 ± 4.3 AU, p=0.01) and mean fluorescence intensity of BAFF-R in non-autoreactive (Day 0: 3232 vs Month 36: 1527, mean difference: 1705, 95%CI: 624 to 2786; p=0.002) as well as on reappearing autoreactive DSG-specific B cells (Day 0: 3873 vs Month 36: 2688, mean difference: 1185, 95%CI: -380 to 2750; p=0.20). Starting high doses of corticosteroids allowed a transitory decrease of serum BAFF levels that re-increased after doses tapering whereas it did not modify BAFF-R expression in autoreactive and non-autoreactive B cells. Our results suggest that the activation of autoreactive B cells at the onset of pemphigus is likely to be related to the presence of high BAFF serum levels and that the decreased BAFF-R expression after rituximab might be responsible for the delayed generation of memory B cells, resulting in a rather long period of mild pemphigus activity after rituximab therapy. Conversely, the incomplete B cell depletion and persistent BAFF-R expression associated with high BAFF serum levels might explain the high number of relapses in patients treated with CS alone.

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Section: Introductionmentioning

confidence: 84%

Modifications of the BAFF/BAFF-Receptor Axis in Patients With Pemphigus Treated With Rituximab Versus Standard Corticosteroid Regimen

et al. 2021

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“…Although the guidelines are clear regarding the use of the oral steroid post infusion of rituximab, [9][10][11] our case turned out to be difficult to manage because when we were trying to scale down prednisone gradually, the patient experienced a recurrence of the skin lesions. The patient was not taking medications or had concomitant malignancies that could trigger the new manifestations.…”

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confidence: 89%

How to decrease systemic corticosteroids in pemphigus patients under rituximab

Picone

Fabbrocini

Megna

2022

Health Science Reports

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How to decrease systemic corticosteroids in pemphigus patients under rituximab Dear Editor, Pemphigus vulgaris (PV) is a chronic autoimmune bullous dermatosis that results from the production of autoantibodies against desmogleins 1 and 3. It is a frequent and often severe form of pemphigus, usually occurring between 40 and 60 years of age. Clinical manifestations begin with blisters and erosions on the oral mucosa, followed by the involvement of other mucous membranes and the development of flaccid blisters on the skin. Systemic corticosteroids and immunosuppressive agents (azathioprine, cyclophosphamide, and mycophenolate mofetil) may be used for PV treatment. 1,2 Recently, the therapeutic armamentarium has been enlarged with the introduction of rituximab, an anti-CD20 immunobiological agent. 3 Rituximab, a chimeric murine/human anti-CD20 monoclonal antibody administered by intravenous (IV) infusion, causes B-cell Health Sci. Rep.

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“…To note, a delayed paradoxical effect of rituximab has been described 53 . A few reports, indeed, describe a worsening of pemphigus immediately after rituximab infusions 48,54 . The reason of this could be due to development of antibodies anti‐chimeric antibodies 48 …”

Section: Therapeutic Approaches and Targets For Treatmentmentioning

confidence: 99%

“…53 A few reports, indeed, describe a worsening of pemphigus immediately after rituximab infusions. 48,54 The reason of this could be due to development of antibodies anti-chimeric antibodies. 48 Rituximab is contraindicated in pregnant or breastfeeding women and in patients affected by hepatitis B or C, HIV, or sepsis.…”

Section: Rituximabmentioning

confidence: 99%

Therapeutic approaches and targets for treatment of autoimmune bullous diseases

Bardazzi

Loi

Marco

et al. 2021

Dermatologic Therapy

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Autoimmune bullous diseases are a heterogeneous group of diseases characterized by the development of cutaneous and mucosal vesicles, blisters, and finally erosions. The common pathogenetic mechanism is the presence of autoantibodies targeting structural proteins of the skin and mucous membranes (demosomes and hemidesmosomes): in the case of pemphigus, the antigens are intraepidermal, whereas in the case of pemphigoid, dermatitis herpetiformis, and epidermolysis bullosa acquisita they are subepidermal. Mucosal involvement typically affects the oral and ocular mucosa, but in some cases, the upper airways or the upper digestive tract are affected. The burden on patients' lives could be severe due to the impairment of normal feeding or breathing. In other cases, they may represent paraneoplastic syndromes. Since autoimmune bullous diseases may result in significant morbidity and mortality, depending on the grade of cutaneous and mucosal involvement, a prompt therapeutic approach is mandatory and, in recalcitrant cases, may be challenging. The first line therapy consists of corticosteroids, both topical and systemic. Once remission or control of the acute phase is obtained, adjuvant therapies need to be introduced in order to spare the corticosteroid load and minimize side effects such as iatrogenic diabetes or osteoporosis. Herein, we describe all current therapeutic approaches to autoimmune bullous diseases, also including emerging therapies.

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Rituximab in practice: Clinical evaluation of patients with pemphigus after rituximab administration

Cited by 12 publications

References 50 publications

Modifications of the BAFF/BAFF-Receptor Axis in Patients With Pemphigus Treated With Rituximab Versus Standard Corticosteroid Regimen

Modifications of the BAFF/BAFF-Receptor Axis in Patients With Pemphigus Treated With Rituximab Versus Standard Corticosteroid Regimen

How to decrease systemic corticosteroids in pemphigus patients under rituximab

Therapeutic approaches and targets for treatment of autoimmune bullous diseases

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