NTRODUCTION
Evidence-based literature regarding management of rare and severe dermatologic disease is limited. Canakinumab and anakinra, two therapeutics used for inhibiting IL-1 pathways, have seen increased utilization for treatment of refractory dermatoses. We sought to better characterize the breadth of dermatologic conditions for which these medications could be utilized. This report is the first to describe a US tertiary care center’s experience of IL-1 blockade for dermatologic use in 23 patients with rare dermatologic conditions as well as refractory adult-onset Still’s disease, systemic sclerosis, Behçet’s disease, and lupus erythematosus. One novel finding in our study is the use of anakinra for treatment of discoid lupus erythematosus in a patient with systemic lupus erythematosus (SLE), supporting IL-1 as a key contributor in the pathogenesis in cutaneous lupus erythematosus.1
Evidence-based, therapeutic modalities for rare, severe dermatologic are lacking. Both canakinumab and anakinra are therapeutics used for inhibiting IL-1 pathways and have seen increased utilization for treatment of refractory dermatoses. We sought to better characterize the breath of conditions for which these medications could be utilized in a tertiary care center. All patients with dermatologic consultation that were treated with anakinra or canakinumab at New York University Langone Health (NYULH) from 2007 to 2019 were evaluated. Patients were excluded if medications were not prescribed for cutaneous indications or insufficient documentation existed to assess response. 53 patients were identified and 30 were excluded. Response to therapy was defined as complete (>75%), partial (25%-75%), or no response (<25%) based upon patient-reported clinical symptoms, physician-identified physical findings, laboratory evaluation, and review of clinical photography.
Tables I and 2 summarize 14 patients treated with anakinra and 9 patients treated with canakinumab, respectively. The mean age was 44 years. The mean total duration of therapy on anakinra was 19.5 months and 15 months for canakinumab. Treatment with anakinra resulted in complete response in 9/14 patients (64%), partial response in 4/14 (29%), and no response in 2/14 (7%).
For canakinumab, 7/10 (70%) patients demonstrated a complete response/remission of disease, while 2/10 (20%) exhibited a partial response and 1 patient was refractory to treatment. In the treatment of SS, AOSD, HIDS, and Behçet’s disease, several patients were transitioned to canakinumab after unsuccessful trials of anakinra, resulting in significant response or resolution. Adverse events from anakinra or canakinumab were infrequent and mild; side effects were not significant enough to withhold therapy.
The mean number of medications prior to initiation of anakinra was 3, while the mean was 2 for canakinumab. The most common medications used concurrently with both anakinra and canakinumab were oral glucocorticoids, methotrexate, and colchicine. Glucocorticoid use changed after implementation of IL-1 blockade. Roughly 48% of patients were able to discontinue glucocorticoids, while 13% required maintenance of >10mg/day, 34% required 5-10mg/day, and 65% required brief courses for flares.
One novel finding in our study is the use of anakinra for treatment of discoid lupus erythematosus in a patient with systemic lupus erythematosus (SLE). IL-1 is key to pathogenesis in cutaneous lupus erythematosus.1 IL-1RA production of cells in patients with SLE shows diminished spontaneous and stimulated responses, which may ultimately perpetuate disease.2 Use of anakinra for SLE is supported by experiments demonstrating that IL-1 antiserum added to SLE monocyte cultures decreases spontaneous IgG synthesis and number of immunoglobulin producing cells.3 It has also shown clinical benefit in treatment of SLE arthropathy.4
Literature regarding management of these rare and refractory dermatologic conditions is limited. This report is the first to describe a US tertiary care center’s experience of IL-1 blockade for dermatologic conditions, supporting the utility of anakinra and canakinumab for rare dermatologic conditions as well as alternative therapies in those with refractory AOSD, SS, Behçet’s disease, and lupus erythematosus.
Evidence-based, therapeutic modalities for rare, severe dermatologic are lacking. Both canakinumab and anakinra are therapeutics used for inhibiting IL-1 pathways and have seen increased utilization for treatment of refractory dermatoses. We sought to better characterize the breath of conditions for which these medications could be utilized in a tertiary care center. All patients with dermatologic consultation that were treated with anakinra or canakinumab at New York University Langone Health (NYULH) from 2007 to 2019 were evaluated. Patients were excluded if medications were not prescribed for cutaneous indications or insufficient documentation existed to assess response. 53 patients were identified and 30 were excluded. Response to therapy was defined as complete (>75%), partial (25%-75%), or no response (<25%) based upon patient-reported clinical symptoms, physician-identified physical findings, laboratory evaluation, and review of clinical photography.
Tables I and 2 summarize 14 patients treated with anakinra and 9 patients treated with canakinumab, respectively. The mean age was 44 years. The mean total duration of therapy on anakinra was 19.5 months and 15 months for canakinumab. Treatment with anakinra resulted in complete response in 9/14 patients (64%), partial response in 4/14 (29%), and no response in 2/14 (7%).
For canakinumab, 7/10 (70%) patients demonstrated a complete response/remission of disease, while 2/10 (20%) exhibited a partial response and 1 patient was refractory to treatment. In the treatment of SS, AOSD, HIDS, and Behçet’s disease, several patients were transitioned to canakinumab after unsuccessful trials of anakinra, resulting in significant response or resolution. Adverse events from anakinra or canakinumab were infrequent and mild; side effects were not significant enough to withhold therapy.
The mean number of medications prior to initiation of anakinra was 3, while the mean was 2 for canakinumab. The most common medications used concurrently with both anakinra and canakinumab were oral glucocorticoids, methotrexate, and colchicine. Glucocorticoid use changed after implementation of IL-1 blockade. Roughly 48% of patients were able to discontinue glucocorticoids, while 13% required maintenance of >10mg/day, 34% required 5-10mg/day, and 65% required brief courses for flares.
One novel finding in our study is the use of anakinra for treatment of discoid lupus erythematosus in a patient with systemic lupus erythematosus (SLE). IL-1 is key to pathogenesis in cutaneous lupus erythematosus.1 IL-1RA production of cells in patients with SLE shows diminished spontaneous and stimulated responses, which may ultimately perpetuate disease.2 Use of anakinra for SLE is supported by experiments demonstrating that IL-1 antiserum added to SLE monocyte cultures decreases spontaneous IgG synthesis and number of immunoglobulin producing cells.3 It has also shown clinical benefit in treatment of SLE arthropathy.4
Literature regarding management of these rare and refractory dermatologic conditions is limited. This report is the first to describe a US tertiary care center’s experience of IL-1 blockade for dermatologic conditions, supporting the utility of anakinra and canakinumab for rare dermatologic conditions as well as alternative therapies in those with refractory AOSD, SS, Behçet’s disease, and lupus erythematosus.
