TWENTY-FIFTH ISSUE
JANUARY 4, 2023
Association of Rituximab With Risk of Long-term Cardiovascular and Metabolic Outcomes in Patients With Pemphigus
JAMA Dermatology
JAMA Dermatology
A rituximab infusion a year keeps the doctor away?
Conventional immunosuppressive agents, such as azathioprine and mycophenolate mofetil (MMF), are considered first line treatment for pemphigus vulgaris. Rituximab, a monoclonal CD20 antibody, is used in the treatment of refractory disease. However, the risk of long-term cardiovascular and metabolic side effects secondary to treatment with these agents has yet to be evaluated. This retrospective cohort study examined 1922 patients with pemphigus vulgaris who were treated with either conventional immunosuppressives (azathioprine/MMF, n=961) or rituximab (n=961) to evaluate for such outcomes. Survival analyses were conducted using the Kaplan-Meier method, survival distribution by log-rank, and hazard ratios via Cox regression model.
The study found that patients in the rituximab group had a lower risk of myocardial infarction (relative risk [RR], 0.45; 95% CI, 0.24-0.86; P = .01), stroke (RR, 0.42; 95% CI, 0.26-0.69; P < .001), peripheral vascular disease (RR, 0.47; 95% CI, 0.28-0.79; P = .003), hypertension (RR, 0.48; 95% CI, 0.38-0.63; P < .001), hyperlipidemia (RR, 0.45; 95% CI, 0.32-0.64; P < .001), type 2 diabetes (RR, 0.63; 95% CI, 0.51-0.77; P < .001), obesity (RR, 0.49; 95% CI, 0.34-0.72; P < .001), and osteoporosis (RR, 0.46; 95% CI, 0.30-0.71; P < .001), as compared with patients treated with conventional agents. No difference existed in all-cause mortality between groups (hazard ratio, 0.94; 95% CI, 0.62-1.43; log-rank P = .77).
Limitations: This study is retrospective in nature. There was no adjustment for the number of rituximab treatment courses and the cumulative exposure to corticosteroids was not quantified. This study was not powered to examine for differences between azathioprine and MMF.
Main Takeaways: The use of rituximab should be considered for the treatment of pemphigus vulgaris in patients with pre-existing cardiovascular or metabolic conditions and risk factors.
Deucravacitinib, a tyrosine kinase 2 inhibitor, demonstrated superiority in a double-blind, randomized trial for achievement of PASI 75 versus patients treated with apremilast or placebo for moderate to severe psoriasis
Journal of The American Academy of Dermatology
Journal of The American Academy of Dermatology
Let’s see what deucravacitinib can DO!
Psoriasis is a common inflammatory skin condition. Previous studies have shown that individuals with loss-of-function mutations in the tyrosine kinase 2 (TYK2) receptor (a signaling molecule for cytokines) have decreased risk of developing psoriasis. To test this theory and apply it to the treatment of psoriasis, researchers compared oral deucravacitinib, a selective TYK2 inhibitor, to apremilast (brand name Otezla) and placebo.
In a double-blind, randomized, 52-week trial, researchers treated 666 patients with moderate to severe psoriasis with either 6 mg of deucravacitinib (n=332), apremilast 30 mg twice daily (an FDA approved oral treatment for psoriasis, n=168), or placebo (n=166) in a 2:1:1 ratio. The primary outcome was skin clearance, measured by Psoriasis Area and Severity Index (PASI) 75 score; achievement of PASI 75 indicates ≥ 75% reduction in severity from baseline. Secondary outcomes included quality of life and adverse event analyses.
Results showed that 58.4% of deucravacitinib patients achieved PASI 75 versus 12.7% of placebo patients (P < 0.0001). Additionally, a higher percentage of deucravacitinib patients achieved PASI 90 versus placebo and apremilast patients at week 16 (35.5% vs 4.2% and 19.6%, respectively; P < 0.0001 vs placebo; P = 0.0002 vs apremilast) and versus the apremilast group at week 24 (42.2% vs 22.0%; P < 0.0001). Quality of life metrics were also significantly improved in patients taking deucravacitinib compared to those taking apremilast and placebo. Adverse event outcomes were similar between all three groups.
Limitations: Limited racial diversity and short study period of one year.
Main Takeaway: Psoriasis patients treated with deucravacitinib had improvement in their psoriasis at a significantly higher rate than patients treated with apremilast or placebo over 52 weeks.
Psoriasis is a common inflammatory skin condition. Previous studies have shown that individuals with loss-of-function mutations in the tyrosine kinase 2 (TYK2) receptor (a signaling molecule for cytokines) have decreased risk of developing psoriasis. To test this theory and apply it to the treatment of psoriasis, researchers compared oral deucravacitinib, a selective TYK2 inhibitor, to apremilast (brand name Otezla) and placebo.
In a double-blind, randomized, 52-week trial, researchers treated 666 patients with moderate to severe psoriasis with either 6 mg of deucravacitinib (n=332), apremilast 30 mg twice daily (an FDA approved oral treatment for psoriasis, n=168), or placebo (n=166) in a 2:1:1 ratio. The primary outcome was skin clearance, measured by Psoriasis Area and Severity Index (PASI) 75 score; achievement of PASI 75 indicates ≥ 75% reduction in severity from baseline. Secondary outcomes included quality of life and adverse event analyses.
Results showed that 58.4% of deucravacitinib patients achieved PASI 75 versus 12.7% of placebo patients (P < 0.0001). Additionally, a higher percentage of deucravacitinib patients achieved PASI 90 versus placebo and apremilast patients at week 16 (35.5% vs 4.2% and 19.6%, respectively; P < 0.0001 vs placebo; P = 0.0002 vs apremilast) and versus the apremilast group at week 24 (42.2% vs 22.0%; P < 0.0001). Quality of life metrics were also significantly improved in patients taking deucravacitinib compared to those taking apremilast and placebo. Adverse event outcomes were similar between all three groups.
Limitations: Limited racial diversity and short study period of one year.
Main Takeaway: Psoriasis patients treated with deucravacitinib had improvement in their psoriasis at a significantly higher rate than patients treated with apremilast or placebo over 52 weeks.
Antibiotic Use and Surgical Site Infections in Immunocompromised Patients After Mohs Micrographic Surgery
Dermatologic Surgery
Immunosuppression: not the Mohst common reason for post-op antibiotics
Immunosuppression is a well-known risk factor for developing cutaneous malignancies. Mohs micrographic surgery (MMS) is the standard of care treatment for high-risk and recurrent nonmelanoma skin cancers and offers the highest rates of cure. Adverse events after MMS are rare, but may include infection, dehiscence, necrosis, and bleeding. Prior studies have resulted in inconclusive evidence about whether immunosuppression places patients at increased risk of postoperative adverse events, such as infection.
Researchers conducted a retrospective review of 5886 patients between ages 44 and 93 who underwent MMS at a single institution over a 7-year period. Data including type of tumor, size, location, repair type, immunosuppression status, and infection were recorded. Patients in the immunosuppressed group (n = 727) included those who were post-transplant (72%), HIV positive (21%), had chronic lymphocytic leukemia/multiple myeloma/other hematogenous malignancy (4%), were on immunosuppression for other chronic conditions (2%), or were neutropenic (1%).
Researchers found that immunosuppressed patients (37.0%) were not significantly more likely to be prescribed antibiotics when compared to immunocompetent patients (34.2%) (p=0.14). Factors associated with increased incidence of antibiotic use included preoperative lesion size >40mm (86.7%) and high-risk lesion location (46.4%). Infection rates were similar between immunosuppressed and immunocompetent patients (2.1% vs 1.6%, p=0.30). In immunosuppressed patients, antibiotic use did not decrease the likelihood of infection (3.0% vs 1.5%, p=0.19).
Limitations: Given the single institution and single surgeon nature of the study, further studies are needed to investigate the efficacy of postoperative antibiotics.
Main Takeaway: This study suggests that immunosuppression is not associated with increased post-Mohs micrographic surgery infection rate, and that postoperative antibiotics should not be indicated in immunosuppressed patients unless other high-risk criteria exist.
Immunosuppression is a well-known risk factor for developing cutaneous malignancies. Mohs micrographic surgery (MMS) is the standard of care treatment for high-risk and recurrent nonmelanoma skin cancers and offers the highest rates of cure. Adverse events after MMS are rare, but may include infection, dehiscence, necrosis, and bleeding. Prior studies have resulted in inconclusive evidence about whether immunosuppression places patients at increased risk of postoperative adverse events, such as infection.
Researchers conducted a retrospective review of 5886 patients between ages 44 and 93 who underwent MMS at a single institution over a 7-year period. Data including type of tumor, size, location, repair type, immunosuppression status, and infection were recorded. Patients in the immunosuppressed group (n = 727) included those who were post-transplant (72%), HIV positive (21%), had chronic lymphocytic leukemia/multiple myeloma/other hematogenous malignancy (4%), were on immunosuppression for other chronic conditions (2%), or were neutropenic (1%).
Researchers found that immunosuppressed patients (37.0%) were not significantly more likely to be prescribed antibiotics when compared to immunocompetent patients (34.2%) (p=0.14). Factors associated with increased incidence of antibiotic use included preoperative lesion size >40mm (86.7%) and high-risk lesion location (46.4%). Infection rates were similar between immunosuppressed and immunocompetent patients (2.1% vs 1.6%, p=0.30). In immunosuppressed patients, antibiotic use did not decrease the likelihood of infection (3.0% vs 1.5%, p=0.19).
Limitations: Given the single institution and single surgeon nature of the study, further studies are needed to investigate the efficacy of postoperative antibiotics.
Main Takeaway: This study suggests that immunosuppression is not associated with increased post-Mohs micrographic surgery infection rate, and that postoperative antibiotics should not be indicated in immunosuppressed patients unless other high-risk criteria exist.
Innovations in dermatology
Ultrasound, more like Ultra Cool!
Cutaneous chronic graft-versus-host disease (cGVHD) is a complication of allogeneic hematopoietic stem cell transplant in which the donated cells attack the recipient’s body. cGVHD can present as either sclerotic or nonsclerotic and the sclerotic form is often detected later in the disease progression. Affected individuals are significantly impaired and must continue immunosuppressive therapy. Because of the morbid progression of this disease, a non-invasive detection system may be helpful to identify and prevent sclerodermatous damage. High-frequency ultrasound (HFUS) is a cost-effective, non-invasive method of monitoring cGVHD advancement and could prove to be very valuable in preventing poor outcomes. In this study, eighteen patients who met 2014 NIH criteria for a clinical diagnosis of cutaneous GVHD and 10 control patients were recruited to test the efficacy of HFUS. Of the 18 GVHD patients recruited, 15 had sclerotic features and 3 had no sclerotic features. Each patient was examined by the same physician using a B-mode color doppler ultrasound with a high resolution linear transducer. Epidermal, dermal, and hypodermal thicknesses were measured in three affected anatomical sites. There was a statistically significant reduction in epidermis and hypodermis thickness in all cGVHD patients at each anatomical site compared to the healthy controls. Additionally, at 3 month follow-up, the 3 patients who had initially had no sclerodermatous features, had developed clinical signs of sclerotic cGVHD. In conclusion, high frequency ultrasound could be a noninvasive approach to early detection of fibrotic skin alterations prior to clinical detection of cGVHD.
Limitations: This study was conducted with a small population, consequently a larger prospective study will be needed to confirm the applicability of these findings.
Cutaneous chronic graft-versus-host disease (cGVHD) is a complication of allogeneic hematopoietic stem cell transplant in which the donated cells attack the recipient’s body. cGVHD can present as either sclerotic or nonsclerotic and the sclerotic form is often detected later in the disease progression. Affected individuals are significantly impaired and must continue immunosuppressive therapy. Because of the morbid progression of this disease, a non-invasive detection system may be helpful to identify and prevent sclerodermatous damage. High-frequency ultrasound (HFUS) is a cost-effective, non-invasive method of monitoring cGVHD advancement and could prove to be very valuable in preventing poor outcomes. In this study, eighteen patients who met 2014 NIH criteria for a clinical diagnosis of cutaneous GVHD and 10 control patients were recruited to test the efficacy of HFUS. Of the 18 GVHD patients recruited, 15 had sclerotic features and 3 had no sclerotic features. Each patient was examined by the same physician using a B-mode color doppler ultrasound with a high resolution linear transducer. Epidermal, dermal, and hypodermal thicknesses were measured in three affected anatomical sites. There was a statistically significant reduction in epidermis and hypodermis thickness in all cGVHD patients at each anatomical site compared to the healthy controls. Additionally, at 3 month follow-up, the 3 patients who had initially had no sclerodermatous features, had developed clinical signs of sclerotic cGVHD. In conclusion, high frequency ultrasound could be a noninvasive approach to early detection of fibrotic skin alterations prior to clinical detection of cGVHD.
Limitations: This study was conducted with a small population, consequently a larger prospective study will be needed to confirm the applicability of these findings.