High-Dose IVIG, Rituximab Effective in Patients With Pemphigoid-Associated Conjunctivitis

In patients with ocular cicatricial pemphigoid (OCP) and mucous membrane pemphigoid with ocular involvement (ocMMP), treatment with high-dose intravenous immunoglobulin (IVIG) and rituximab (Rituxan; Genentech and Biogen Idec) was found to be effective at managing cicatrizing conjunctivitis, especially in those with severe recalcitrant disease, according to new data published in AJO International.¹

Conjunctivitis associated with ocular cicatricial pemphigoid can be painful and vision-threatening. | Image Credit: © andrei310 | stock.adobe.com

OCP, a subset of the autoimmune blistering disease mucous membrane pemphigoid (MMP), is isolated to the ocular mucosal surface. Symptoms of the disease can include a foreign body sensation, redness, and dry eyes with conjunctival scarring, which is a potentially vision-threatening complication. It can progress from fibrosis to symblepharon formation, keratinization of the cornea and, ultimately, permanent vision loss.²

Corticosteroids represent the only FDA-approved treatment for OCP, but prolonged use can lead to complications. The utilization of treatments that spare steroids while providing systemic immunosuppression would be ideal for treating the disease while preventing adverse events (AEs). One such treatment, IVIG, has been previously reported as a treatment for OCP in case studies.¹

The use of IVIG, in combination with rituximab, for treatment of OCP/ocMMP is off-label, with most published data being limited in nature and oftentimes not addressing the potential utility of the combination in treating ocular manifestations of the disease. In this trial, the investigators sought to describe the use of IVIG/rituximab in the treatment of recalcitrant ocular disease in OCP/ocMMP through a retrospective review of case studies.¹

Ocular clinical response to IVIG/rituximab was defined by the degree of hyperemia on a slit lamp exam, while treatment response was determined by the highest degree of response achieved at any point during the treatment course. Responses were defined as no response, partial response, clinical remission, steroid-free remission, and durable remission.¹

In total, 112 patients with OCP/ocMMP examined in the literature search, of whom 31 (27.7%) underwent IVIG/rituximab treatment. The investigators found that access to rituximab and IVIG and its related dosing was limited by insurance approval. Still, the patients successfully underwent their assigned regimens, varying between differing doses of rituximab and IVIG.¹

Across all patients, the highest achieved clinical response reached during treatment was steroid-free remission (11, 35.5%), followed by a partial response (10, 32.3%), clinical remission with use of corticosteroids (6, 19.4%), durable remission (2, 6.5%), and no response (2, 6.5%). Mean time to remission for the eligible patients was 9.0 months (range 1-26). Notably, the investigators documented an overall decrease in systemic corticosteroid use, with a 51.3% average reduction in prednisone dosage after initiation of rituximab/IVIG therapy.¹

The mean time to relapse was 32 months (range 2-62 months). In a critical development, of those who developed any degree of clinical remission (19, 61.3%), 12 (63.2%) had a relapse in disease activity, according to the investigators. Additionally, relapse occurred off therapy for 3 individuals (25%), during an attempted rituximab extension for 3 participants (25%), and while on maintenance therapy for 6 patients (50%). However, 9 (75%) patients successfully regained remission using a variety of strategies, including decreasing the interval between rituximab infusions or switching agents.¹

AEs to the rituximab/IVIG combination included headache, weakness, hypertension, joint pain, and rash. Five AEs were reported to the investigators, including a patient that developed neutropenia following treatment initiation and another who suffered a cerebral ischemic event 2 weeks following IVIG maintenance.¹

The investigators observed 29 (93.5%) patients with a positive response to rituximab and IVIG as a treatment for their ocular and systemic signs, which they said was like those of previously conducted small case reports, which have reported remission rates of 71% to 100%. They cautioned that treatment was reserved for the most severe and recalcitrant cases in their practice, which could make any determined response rates not generalizable to the ocular pemphigoid population at large.¹

Furthermore, the authors recommend “judicious use” of the combination in this population due to risk of serious AEs, emphasizing “thorough counseling of risks, benefits, and alternatives,” prior to the initiation of such a treatment.¹

REFERENCES

1. Johnny B, Thompson K, Eziama E, et al. Rituximab and intravenous immunoglobulin in the treatment of cicatrizing conjunctivitis associated with pemphigoid. AJO International. Available online November 30, 2024. doi:10.1016/j.ajoint.2024.100087

2. Stan C, Diaconu E, Hoprica L, et al. Ocular cicatricial pemphigoid. Rom J Ophthalmol. 2020;64(2):226-230. PMCID:PMC7339695