Consider Infliximab for Refractory Cutaneous Sarcoidosis

SEOUL, SOUTH KOREA – Infliximab appears to be an effective corticosteroid-sparing treatment for patients with refractory cutaneous sarcoidosis, albeit an off-label one.

"Infliximab seems to be a good candidate as third-line therapy for refractory cutaneous sarcoidosis. We recommend a continuous evaluation of clinical response and an increase in infliximab dosing up to 10 mg/kg every 4 weeks in cases of insufficient response [as well as] the use of concomitant low-dose methotrexate to increase infliximab efficacy and prevent the development of anti-infliximab antibodies," noted Dr. Fabien Guibal at the World Congress of Dermatology.

Skin involvement is common in sarcoidosis, affecting up to 30% of patients. It carries substantial morbidity, and treatment options are limited. Systemic corticosteroids are the mainstay, but the associated side effects are well known. Methotrexate is a good second-line therapy, although the response is highly variable. Azathioprine, antimalarials, and thalidomide are among the alternative options, noted Dr. Guibal of Hôpital Saint-Louis, Paris.

He presented a retrospective, single-center study involving nine patients placed on infliximab (Remicade) for refractory cutaneous sarcoidosis. Participants had failed to improve on a median of five prior immunosuppressive drugs.

The subjects (eight women and one man) were a median of 43 years old when diagnosed with sarcoidosis, and 51 years of age when they started on infliximab. The cutaneous lesions consisted of lupus pernio in eight patients, disseminated papules in seven, and a large facial plaque in one. All patients had extracutaneous disease, including pulmonary sarcoidosis in eight individuals and CNS involvement in one.

The impetus for turning to the tumor necrosis factor–alpha inhibitor in these nine patients was the fact that TNF-alpha is known to be a critical cytokine in the formation and maintenance of granulomas. Plus, there have been several reports of favorable treatment responses in patients with pulmonary sarcoidosis and other internal organ involvement.

Three of nine patients experienced resolution of cutaneous lesions on their first course of infliximab. Another four had near-resolution, and the remaining two patients showed partial improvement. The median lag time until maximal response was 12 weeks (range, 2-22 weeks).

When infliximab was eventually discontinued in six patients, five relapsed after a median 9 weeks off the drug. The sole patient who didn’t relapse had successfully replaced the biologic agent with methotrexate.

The five relapsers underwent a second course of infliximab. Four experienced near-resolution of their cutaneous disease, and the fifth showed lesion stabilization. Three of them eventually discontinued infliximab, one because of loss of efficacy, another who remained relapse free while replacing the biologic with methotrexate, and a third who was lost to follow-up.

After a median 34 months of follow-up, five of the nine patients remain on infliximab. Their average oral prednisone dose is half of the 12 mg/day it was before they started taking infliximab. No serious adverse effects have occurred.

Dr. Guibal declared having no relevant financial relationships.

SEOUL, SOUTH KOREA – Infliximab appears to be an effective corticosteroid-sparing treatment for patients with refractory cutaneous sarcoidosis, albeit an off-label one.

"Infliximab seems to be a good candidate as third-line therapy for refractory cutaneous sarcoidosis. We recommend a continuous evaluation of clinical response and an increase in infliximab dosing up to 10 mg/kg every 4 weeks in cases of insufficient response [as well as] the use of concomitant low-dose methotrexate to increase infliximab efficacy and prevent the development of anti-infliximab antibodies," noted Dr. Fabien Guibal at the World Congress of Dermatology.

Skin involvement is common in sarcoidosis, affecting up to 30% of patients. It carries substantial morbidity, and treatment options are limited. Systemic corticosteroids are the mainstay, but the associated side effects are well known. Methotrexate is a good second-line therapy, although the response is highly variable. Azathioprine, antimalarials, and thalidomide are among the alternative options, noted Dr. Guibal of Hôpital Saint-Louis, Paris.

He presented a retrospective, single-center study involving nine patients placed on infliximab (Remicade) for refractory cutaneous sarcoidosis. Participants had failed to improve on a median of five prior immunosuppressive drugs.

The subjects (eight women and one man) were a median of 43 years old when diagnosed with sarcoidosis, and 51 years of age when they started on infliximab. The cutaneous lesions consisted of lupus pernio in eight patients, disseminated papules in seven, and a large facial plaque in one. All patients had extracutaneous disease, including pulmonary sarcoidosis in eight individuals and CNS involvement in one.

The impetus for turning to the tumor necrosis factor–alpha inhibitor in these nine patients was the fact that TNF-alpha is known to be a critical cytokine in the formation and maintenance of granulomas. Plus, there have been several reports of favorable treatment responses in patients with pulmonary sarcoidosis and other internal organ involvement.

Three of nine patients experienced resolution of cutaneous lesions on their first course of infliximab. Another four had near-resolution, and the remaining two patients showed partial improvement. The median lag time until maximal response was 12 weeks (range, 2-22 weeks).

When infliximab was eventually discontinued in six patients, five relapsed after a median 9 weeks off the drug. The sole patient who didn’t relapse had successfully replaced the biologic agent with methotrexate.

The five relapsers underwent a second course of infliximab. Four experienced near-resolution of their cutaneous disease, and the fifth showed lesion stabilization. Three of them eventually discontinued infliximab, one because of loss of efficacy, another who remained relapse free while replacing the biologic with methotrexate, and a third who was lost to follow-up.

After a median 34 months of follow-up, five of the nine patients remain on infliximab. Their average oral prednisone dose is half of the 12 mg/day it was before they started taking infliximab. No serious adverse effects have occurred.

Dr. Guibal declared having no relevant financial relationships.

SEOUL, SOUTH KOREA – Infliximab appears to be an effective corticosteroid-sparing treatment for patients with refractory cutaneous sarcoidosis, albeit an off-label one.

"Infliximab seems to be a good candidate as third-line therapy for refractory cutaneous sarcoidosis. We recommend a continuous evaluation of clinical response and an increase in infliximab dosing up to 10 mg/kg every 4 weeks in cases of insufficient response [as well as] the use of concomitant low-dose methotrexate to increase infliximab efficacy and prevent the development of anti-infliximab antibodies," noted Dr. Fabien Guibal at the World Congress of Dermatology.

Skin involvement is common in sarcoidosis, affecting up to 30% of patients. It carries substantial morbidity, and treatment options are limited. Systemic corticosteroids are the mainstay, but the associated side effects are well known. Methotrexate is a good second-line therapy, although the response is highly variable. Azathioprine, antimalarials, and thalidomide are among the alternative options, noted Dr. Guibal of Hôpital Saint-Louis, Paris.

He presented a retrospective, single-center study involving nine patients placed on infliximab (Remicade) for refractory cutaneous sarcoidosis. Participants had failed to improve on a median of five prior immunosuppressive drugs.

The subjects (eight women and one man) were a median of 43 years old when diagnosed with sarcoidosis, and 51 years of age when they started on infliximab. The cutaneous lesions consisted of lupus pernio in eight patients, disseminated papules in seven, and a large facial plaque in one. All patients had extracutaneous disease, including pulmonary sarcoidosis in eight individuals and CNS involvement in one.

The impetus for turning to the tumor necrosis factor–alpha inhibitor in these nine patients was the fact that TNF-alpha is known to be a critical cytokine in the formation and maintenance of granulomas. Plus, there have been several reports of favorable treatment responses in patients with pulmonary sarcoidosis and other internal organ involvement.

Three of nine patients experienced resolution of cutaneous lesions on their first course of infliximab. Another four had near-resolution, and the remaining two patients showed partial improvement. The median lag time until maximal response was 12 weeks (range, 2-22 weeks).

When infliximab was eventually discontinued in six patients, five relapsed after a median 9 weeks off the drug. The sole patient who didn’t relapse had successfully replaced the biologic agent with methotrexate.

The five relapsers underwent a second course of infliximab. Four experienced near-resolution of their cutaneous disease, and the fifth showed lesion stabilization. Three of them eventually discontinued infliximab, one because of loss of efficacy, another who remained relapse free while replacing the biologic with methotrexate, and a third who was lost to follow-up.

After a median 34 months of follow-up, five of the nine patients remain on infliximab. Their average oral prednisone dose is half of the 12 mg/day it was before they started taking infliximab. No serious adverse effects have occurred.

Dr. Guibal declared having no relevant financial relationships.