Article

THE DIAGNOSIS: Neutrophilic Eccrine Hidradenitis

A biopsy from the left preauricular cheek demonstrated dermal neutrophilic inflammation around eccrine coils with focal necrosis (Figure). No notable diffuse dermal neutrophilic infiltrate was present, ruling out Sweet syndrome, and no notable interstitial neutrophilic infiltrate was present, making cellulitis and erysipelas less likely; panculture of tissue also was negative.^1,2 Atypical cells in the deep dermis were positive for CD163 and negative for CD117, CD34, CD123, and myeloperoxidase, consistent with a diagnosis of neutrophilic eccrine hidradenitis (NEH) and reactive histiocytes.³ Treatment with oral prednisone resulted in rapid improvement of symptoms.

Neutrophilic eccrine hidradenitis is a rare reactive neutrophilic dermatosis characterized by eccrine gland involvement. This benign and self-limited condition presents as asymmetric erythematous papules and plaques.² Among 8 granulocytopenic patients with neutrophilic dermatoses, 5 were diagnosed with NEH.⁴ Although first identified in 1982, NEH remains poorly understood.² Initial theories suggested that NEH developed due to cytotoxic substances secreted in sweat glands causing necrosis and neutrophil chemotaxis; however, chemotherapy exposure cannot be linked to every case of NEH. Neutrophilic eccrine hidradenitis can be extremely difficult to differentiate clinically from conditions such as cellulitis and Sweet syndrome.

A patient history can be helpful in identifying triggering factors. Neutrophilic eccrine hidradenitis most commonly is associated with malignant, drug-induced, or infectious triggers, while Sweet syndrome has a broad range of associations including infections, vaccines, inflammatory bowel disease, pregnancy, malignancy, and drug-induced etiologies (Table).¹ On average, NEH presents 10 days after chemotherapy induction, with 70% of cases presenting after the first chemotherapy cycle.⁵ Bacterial cellulitis or erysipelas have an infectious etiology, and patients may report symptoms such as fever, chills, or malaise. Immunosuppressed patients are at greater risk for infection; therefore, clinical signs of infection in a granulocytopenic patient should be addressed urgently.

Physical examination may have limited value in differentiating between these diagnoses, as neutrophilic dermatoses notoriously mimic infection. Cutaneous lesions can appear as pruritic or tender erythematous plaques, papules, or nodules in these conditions, though cellulitis and erysipelas tend to be unilateral and may have associated purulence or inflamed skin lymphatics. Given the potential for misdiagnosis, approaching patients with a broad differential can be helpful. In our patient, the differential diagnosis included Sweet syndrome, NEH, bacterial cellulitis, erysipelas, leukemia cutis, sarcoid, and eosinophilic cellulitis.

Leukemia cutis refers to the infiltration of neoplastic leukocytes in the skin and often occurs in patients with peripheral leukemia, most often acute myeloid leukemia or chronic lymphocytic leukemia. Patients with leukemia cutis often have a worse prognosis, as this finding signifies extramedullary spread of disease.⁶ Clinically, lesions can appear similar to those seen in our patient, though they typically are not symptomatic, can be nodular, tend to exhibit a violaceous hue, and occasionally may be hemorrhagic. Wells syndrome (also known as eosinophilic cellulitis) is an inflammatory dermatosis that presents as painful or pruritic, edematous and erythematous plaques.^7,8 A green hue on resolution is present in some cases and may help clinicians differentiate this disease from mimickers.⁷ Often, eosinophilic cellulitis is misdiagnosed as bacterial cellulitis and treated with antibiotics. The presence of systemic symptoms such as fever or arthralgia is more typical of bacterial cellulitis, erysipelas, eosinophilic cellulitis, or Sweet syndrome than of NEH.¹ Additionally, inflammatory markers (ie, C-reactive protein) and white blood cell counts tend to be elevated in bacterial cellulitis and Sweet syndrome, while leukopenia often is seen in NEH.

Histopathology is crucial in distinguishing these disease etiologies. Neutrophilic eccrine hidradenitis is diagnosed by the characteristic neutrophilic infiltrate and necrosis surrounding eccrine glands and coils. There also may be occasional intraductal abscesses and syringosquamous metaplasia of the sweat glands along with fibrosis of the adjacent dermis. In contrast, histologic sections of Sweet syndrome show numerous mature neutrophils infiltrating the dermis with marked papillary dermal edema. The histopathology of bacterial cellulitis and erysipelas is less specific, but common features include dermal edema, lymphatic dilation, and a diffuse neutrophilic infiltrate surrounding blood vessels. Pathogenic organisms may be seen on histopathology but are not required for the diagnosis of bacterial cellulitis or erysipelas.² Additionally, blood and tissue culture can assist in identification of both the source of infection and the causative organism, but cultures may not always be positive. 

Comparatively, the histopathologic features of eosinophilic cellulitis include dermal edema, eosinophilic infiltration, and flame figures that form when eosinophils degranulate and coat collagen fibers with major basic protein. Flame figures are characteristic but not pathognomonic for eosinophilic cellulitis.⁷ The histopathology of leukemia cutis varies based on the leukemia classification; generally, in acute myeloid leukemia the infiltrate is composed of neoplastic cells in the early stages of development that are positive for myeloid markers such as myeloperoxidase. Atypical and immature granulocytes within the leukocytic infiltrate differentiate this condition from the other diagnoses. Treatment may entail chemotherapy or radiotherapy, and this diagnosis generally carries the worst prognosis of all the conditions in the differential.⁶

Differentiating between these conditions is important in guiding treatment, especially in patients with febrile neutropenia. Unnecessary steroids in immunosuppressed patients can be dangerous, especially if the patient has an infection such as bacterial cellulitis. Furthermore, unwarranted antibiotic use for noninfectious conditions may expose patients to substantial side effects and not improve the condition. Neutrophilic eccrine hidradenitis typically is self-limited and treated symptomatically with systemic corticosteroids and nonsteroidal anti-inflammatory drugs.³ Sweet syndrome often requires a longer course of oral steroids. Leukemia cutis worsens as the leukemia advances, and treatment of the underlying malignancy is the most effective treatment.⁹

Early and accurate recognition of the diagnosis can prevent harmful diagnostic delay, unnecessary antibiotic use, or extended steroid taper in neutropenic patients. Appreciating the differences between these diagnoses can assist clinicians in investigating and tailoring a broad differential to specific patient presentations, which is especially critical when considering common mimickers for life-threatening conditions.

THE DIAGNOSIS: Neutrophilic Eccrine Hidradenitis

A biopsy from the left preauricular cheek demonstrated dermal neutrophilic inflammation around eccrine coils with focal necrosis (Figure). No notable diffuse dermal neutrophilic infiltrate was present, ruling out Sweet syndrome, and no notable interstitial neutrophilic infiltrate was present, making cellulitis and erysipelas less likely; panculture of tissue also was negative.^1,2 Atypical cells in the deep dermis were positive for CD163 and negative for CD117, CD34, CD123, and myeloperoxidase, consistent with a diagnosis of neutrophilic eccrine hidradenitis (NEH) and reactive histiocytes.³ Treatment with oral prednisone resulted in rapid improvement of symptoms.

Neutrophilic eccrine hidradenitis is a rare reactive neutrophilic dermatosis characterized by eccrine gland involvement. This benign and self-limited condition presents as asymmetric erythematous papules and plaques.² Among 8 granulocytopenic patients with neutrophilic dermatoses, 5 were diagnosed with NEH.⁴ Although first identified in 1982, NEH remains poorly understood.² Initial theories suggested that NEH developed due to cytotoxic substances secreted in sweat glands causing necrosis and neutrophil chemotaxis; however, chemotherapy exposure cannot be linked to every case of NEH. Neutrophilic eccrine hidradenitis can be extremely difficult to differentiate clinically from conditions such as cellulitis and Sweet syndrome.

A patient history can be helpful in identifying triggering factors. Neutrophilic eccrine hidradenitis most commonly is associated with malignant, drug-induced, or infectious triggers, while Sweet syndrome has a broad range of associations including infections, vaccines, inflammatory bowel disease, pregnancy, malignancy, and drug-induced etiologies (Table).¹ On average, NEH presents 10 days after chemotherapy induction, with 70% of cases presenting after the first chemotherapy cycle.⁵ Bacterial cellulitis or erysipelas have an infectious etiology, and patients may report symptoms such as fever, chills, or malaise. Immunosuppressed patients are at greater risk for infection; therefore, clinical signs of infection in a granulocytopenic patient should be addressed urgently.

Physical examination may have limited value in differentiating between these diagnoses, as neutrophilic dermatoses notoriously mimic infection. Cutaneous lesions can appear as pruritic or tender erythematous plaques, papules, or nodules in these conditions, though cellulitis and erysipelas tend to be unilateral and may have associated purulence or inflamed skin lymphatics. Given the potential for misdiagnosis, approaching patients with a broad differential can be helpful. In our patient, the differential diagnosis included Sweet syndrome, NEH, bacterial cellulitis, erysipelas, leukemia cutis, sarcoid, and eosinophilic cellulitis.

Leukemia cutis refers to the infiltration of neoplastic leukocytes in the skin and often occurs in patients with peripheral leukemia, most often acute myeloid leukemia or chronic lymphocytic leukemia. Patients with leukemia cutis often have a worse prognosis, as this finding signifies extramedullary spread of disease.⁶ Clinically, lesions can appear similar to those seen in our patient, though they typically are not symptomatic, can be nodular, tend to exhibit a violaceous hue, and occasionally may be hemorrhagic. Wells syndrome (also known as eosinophilic cellulitis) is an inflammatory dermatosis that presents as painful or pruritic, edematous and erythematous plaques.^7,8 A green hue on resolution is present in some cases and may help clinicians differentiate this disease from mimickers.⁷ Often, eosinophilic cellulitis is misdiagnosed as bacterial cellulitis and treated with antibiotics. The presence of systemic symptoms such as fever or arthralgia is more typical of bacterial cellulitis, erysipelas, eosinophilic cellulitis, or Sweet syndrome than of NEH.¹ Additionally, inflammatory markers (ie, C-reactive protein) and white blood cell counts tend to be elevated in bacterial cellulitis and Sweet syndrome, while leukopenia often is seen in NEH.

Histopathology is crucial in distinguishing these disease etiologies. Neutrophilic eccrine hidradenitis is diagnosed by the characteristic neutrophilic infiltrate and necrosis surrounding eccrine glands and coils. There also may be occasional intraductal abscesses and syringosquamous metaplasia of the sweat glands along with fibrosis of the adjacent dermis. In contrast, histologic sections of Sweet syndrome show numerous mature neutrophils infiltrating the dermis with marked papillary dermal edema. The histopathology of bacterial cellulitis and erysipelas is less specific, but common features include dermal edema, lymphatic dilation, and a diffuse neutrophilic infiltrate surrounding blood vessels. Pathogenic organisms may be seen on histopathology but are not required for the diagnosis of bacterial cellulitis or erysipelas.² Additionally, blood and tissue culture can assist in identification of both the source of infection and the causative organism, but cultures may not always be positive. 

Comparatively, the histopathologic features of eosinophilic cellulitis include dermal edema, eosinophilic infiltration, and flame figures that form when eosinophils degranulate and coat collagen fibers with major basic protein. Flame figures are characteristic but not pathognomonic for eosinophilic cellulitis.⁷ The histopathology of leukemia cutis varies based on the leukemia classification; generally, in acute myeloid leukemia the infiltrate is composed of neoplastic cells in the early stages of development that are positive for myeloid markers such as myeloperoxidase. Atypical and immature granulocytes within the leukocytic infiltrate differentiate this condition from the other diagnoses. Treatment may entail chemotherapy or radiotherapy, and this diagnosis generally carries the worst prognosis of all the conditions in the differential.⁶

Differentiating between these conditions is important in guiding treatment, especially in patients with febrile neutropenia. Unnecessary steroids in immunosuppressed patients can be dangerous, especially if the patient has an infection such as bacterial cellulitis. Furthermore, unwarranted antibiotic use for noninfectious conditions may expose patients to substantial side effects and not improve the condition. Neutrophilic eccrine hidradenitis typically is self-limited and treated symptomatically with systemic corticosteroids and nonsteroidal anti-inflammatory drugs.³ Sweet syndrome often requires a longer course of oral steroids. Leukemia cutis worsens as the leukemia advances, and treatment of the underlying malignancy is the most effective treatment.⁹

Early and accurate recognition of the diagnosis can prevent harmful diagnostic delay, unnecessary antibiotic use, or extended steroid taper in neutropenic patients. Appreciating the differences between these diagnoses can assist clinicians in investigating and tailoring a broad differential to specific patient presentations, which is especially critical when considering common mimickers for life-threatening conditions.

THE DIAGNOSIS: Neutrophilic Eccrine Hidradenitis

A biopsy from the left preauricular cheek demonstrated dermal neutrophilic inflammation around eccrine coils with focal necrosis (Figure). No notable diffuse dermal neutrophilic infiltrate was present, ruling out Sweet syndrome, and no notable interstitial neutrophilic infiltrate was present, making cellulitis and erysipelas less likely; panculture of tissue also was negative.^1,2 Atypical cells in the deep dermis were positive for CD163 and negative for CD117, CD34, CD123, and myeloperoxidase, consistent with a diagnosis of neutrophilic eccrine hidradenitis (NEH) and reactive histiocytes.³ Treatment with oral prednisone resulted in rapid improvement of symptoms.

Neutrophilic eccrine hidradenitis is a rare reactive neutrophilic dermatosis characterized by eccrine gland involvement. This benign and self-limited condition presents as asymmetric erythematous papules and plaques.² Among 8 granulocytopenic patients with neutrophilic dermatoses, 5 were diagnosed with NEH.⁴ Although first identified in 1982, NEH remains poorly understood.² Initial theories suggested that NEH developed due to cytotoxic substances secreted in sweat glands causing necrosis and neutrophil chemotaxis; however, chemotherapy exposure cannot be linked to every case of NEH. Neutrophilic eccrine hidradenitis can be extremely difficult to differentiate clinically from conditions such as cellulitis and Sweet syndrome.

A patient history can be helpful in identifying triggering factors. Neutrophilic eccrine hidradenitis most commonly is associated with malignant, drug-induced, or infectious triggers, while Sweet syndrome has a broad range of associations including infections, vaccines, inflammatory bowel disease, pregnancy, malignancy, and drug-induced etiologies (Table).¹ On average, NEH presents 10 days after chemotherapy induction, with 70% of cases presenting after the first chemotherapy cycle.⁵ Bacterial cellulitis or erysipelas have an infectious etiology, and patients may report symptoms such as fever, chills, or malaise. Immunosuppressed patients are at greater risk for infection; therefore, clinical signs of infection in a granulocytopenic patient should be addressed urgently.

Physical examination may have limited value in differentiating between these diagnoses, as neutrophilic dermatoses notoriously mimic infection. Cutaneous lesions can appear as pruritic or tender erythematous plaques, papules, or nodules in these conditions, though cellulitis and erysipelas tend to be unilateral and may have associated purulence or inflamed skin lymphatics. Given the potential for misdiagnosis, approaching patients with a broad differential can be helpful. In our patient, the differential diagnosis included Sweet syndrome, NEH, bacterial cellulitis, erysipelas, leukemia cutis, sarcoid, and eosinophilic cellulitis.

Leukemia cutis refers to the infiltration of neoplastic leukocytes in the skin and often occurs in patients with peripheral leukemia, most often acute myeloid leukemia or chronic lymphocytic leukemia. Patients with leukemia cutis often have a worse prognosis, as this finding signifies extramedullary spread of disease.⁶ Clinically, lesions can appear similar to those seen in our patient, though they typically are not symptomatic, can be nodular, tend to exhibit a violaceous hue, and occasionally may be hemorrhagic. Wells syndrome (also known as eosinophilic cellulitis) is an inflammatory dermatosis that presents as painful or pruritic, edematous and erythematous plaques.^7,8 A green hue on resolution is present in some cases and may help clinicians differentiate this disease from mimickers.⁷ Often, eosinophilic cellulitis is misdiagnosed as bacterial cellulitis and treated with antibiotics. The presence of systemic symptoms such as fever or arthralgia is more typical of bacterial cellulitis, erysipelas, eosinophilic cellulitis, or Sweet syndrome than of NEH.¹ Additionally, inflammatory markers (ie, C-reactive protein) and white blood cell counts tend to be elevated in bacterial cellulitis and Sweet syndrome, while leukopenia often is seen in NEH.

Histopathology is crucial in distinguishing these disease etiologies. Neutrophilic eccrine hidradenitis is diagnosed by the characteristic neutrophilic infiltrate and necrosis surrounding eccrine glands and coils. There also may be occasional intraductal abscesses and syringosquamous metaplasia of the sweat glands along with fibrosis of the adjacent dermis. In contrast, histologic sections of Sweet syndrome show numerous mature neutrophils infiltrating the dermis with marked papillary dermal edema. The histopathology of bacterial cellulitis and erysipelas is less specific, but common features include dermal edema, lymphatic dilation, and a diffuse neutrophilic infiltrate surrounding blood vessels. Pathogenic organisms may be seen on histopathology but are not required for the diagnosis of bacterial cellulitis or erysipelas.² Additionally, blood and tissue culture can assist in identification of both the source of infection and the causative organism, but cultures may not always be positive. 

Comparatively, the histopathologic features of eosinophilic cellulitis include dermal edema, eosinophilic infiltration, and flame figures that form when eosinophils degranulate and coat collagen fibers with major basic protein. Flame figures are characteristic but not pathognomonic for eosinophilic cellulitis.⁷ The histopathology of leukemia cutis varies based on the leukemia classification; generally, in acute myeloid leukemia the infiltrate is composed of neoplastic cells in the early stages of development that are positive for myeloid markers such as myeloperoxidase. Atypical and immature granulocytes within the leukocytic infiltrate differentiate this condition from the other diagnoses. Treatment may entail chemotherapy or radiotherapy, and this diagnosis generally carries the worst prognosis of all the conditions in the differential.⁶

Differentiating between these conditions is important in guiding treatment, especially in patients with febrile neutropenia. Unnecessary steroids in immunosuppressed patients can be dangerous, especially if the patient has an infection such as bacterial cellulitis. Furthermore, unwarranted antibiotic use for noninfectious conditions may expose patients to substantial side effects and not improve the condition. Neutrophilic eccrine hidradenitis typically is self-limited and treated symptomatically with systemic corticosteroids and nonsteroidal anti-inflammatory drugs.³ Sweet syndrome often requires a longer course of oral steroids. Leukemia cutis worsens as the leukemia advances, and treatment of the underlying malignancy is the most effective treatment.⁹

Early and accurate recognition of the diagnosis can prevent harmful diagnostic delay, unnecessary antibiotic use, or extended steroid taper in neutropenic patients. Appreciating the differences between these diagnoses can assist clinicians in investigating and tailoring a broad differential to specific patient presentations, which is especially critical when considering common mimickers for life-threatening conditions.

In 2022, the most significant advances in the treatment of gynecologic cancers were achieved for patients with ovarian cancer. While ovarian cancer continues to carry the worst prognosis of all gynecologic cancers, 5-year relative survival has gradually increased, from 34.4% in 1975 to 52.4% in 2014.¹

In this Update, we highlight the recent advances in our understanding of targeted therapy in ovarian cancer. We review SORAYA, a trial that demonstrated that mirvetuximab soravtansine, an antibody-drug conjugate, has promising efficacy in platinum-resistant ovarian cancers that overexpress folate receptor α. We also spotlight progress in the treatment of low-grade serous ovarian cancer, another notoriously chemotherapy-resistant disease, in GOG 281/LOGS, a phase 2 study of the MEK inhibitor trametinib. Finally, we discuss emerging long-term follow-up data on poly(ADP-ribose) polymerase (PARP) inhibitors, which are helping to refine the role of these groundbreaking drugs.

New drug approved for platinum-resistant epithelial ovarian cancer—the first since 2014

Matulonis UA, Lorusso D, Oaknin A, et al. Efficacy and safety of mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer with high folate receptor alpha expression: results from the SORAYA study. J Clin Oncol. 2023;41:2436-2445. doi:10.1200/JCO.22.01900.

While most patients diagnosed with advanced ovarian cancer will respond to platinum-based chemotherapy, those whose disease recurs eventually develop resistance to platinum agents. Treatment options for platinum-resistant ovarian cancer are limited and prognosis is poor. Most regimens have a response rate of only 10%. Since the approval of bevacizumab combined with chemotherapy in 2014, no new agents have been approved by the US Food and Drug Administration (FDA) for use in platinum-resistant ovarian cancer.

Efficacy shown with mirvetuximab

Recently, Matulonis and colleagues published results of the SORAYA study, a single-arm,phase 2 trial, that examined the efficacy and safety of mirvetuximab soravtansine-gynx among women with platinum-resistant ovarian cancer.² Mirvetuximab is an antibody-drug conjugate composed of an antibody directed at the folate receptor α attached to a cytotoxic microtubule inhibitor.

The study included 106 patients with platinum-resistant ovarian cancer whose tumors expressed folate receptor α at a high level—a feature of approximately 50% of patients screened for the study. Twenty-nine patients experienced a partial response and 5 had a complete response, corresponding to a remarkable objective response rate of 32.4%. The median progression-free survival was 4.3 months.

Like other antibody-drug conjugates, ocular toxicities, including blurred vision (41%) and keratopathy (29%), were common. However, toxicity was manageable and rarely led to drug discontinuation.

Continue to: A novel agent for recurrent low-grade serous ovarian carcinoma...

A novel agent for recurrent low-grade serous ovarian carcinoma

Gershenson DM, Miller A, Brady WE, et al. Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial. Lancet. 2022;399:541-553. doi:10.1016/S0140-6736(21)02175-9.

Low-grade serous carcinoma is a histologic subtype that makes up approximately 5% of all epithelial ovarian cancers.³ Patients with low-grade serous carcinoma are often younger and, because of the indolent nature of the histology, generally have a longer overall survival compared with patients with high-grade serous carcinoma. Unlike high-grade disease, however, low-grade serous carcinoma usually is resistant to chemotherapy, making treatment options limited for patients with advanced and recurrent disease.

Trametinib: A potential option

In an international, randomized, open-label trial (GOG 281/LOGS), Gershenson and colleagues investigated the efficacy of trametinib compared with standard-of-care chemotherapy in patients with recurrent low-grade serous ovarian cancer.⁴ Trametinib, a mitogen-activated protein kinase MEK inhibitor, is a targeted agent that is FDA approved for treatment in BRAF-mutated melanoma, lung, and thyroid cancers.

Patients with recurrent low-grade serous ovarian cancer were randomly assigned to trametinib (n = 130) or 1 of 5 standard-of-care treatment options (n = 130), including both chemotherapy and hormonal treatments. Those assigned to trametinib were significantly less likely to have disease progression (78% vs 89%), with a median progression-free survival of 13 months, compared with7.2 months in controls (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.36–0.64). Additionally, patients who had a radiographic response to trametinib experienced a longer duration of response compared with those who responded to standard-of-care treatment (13.6 months vs 5.9 months).

While there was no statistically significant difference in overall survival (HR, 0.76; 95% CI, 0.51–1.12), crossover to trametinib from the standard-of-care group was allowed and occurred among 68% of patients, which limits the study’s ability to measure differences in overall survival.

Trametinib was well tolerated by patients, but skin rash and anemia followed by hypertension were the most common adverse effects. In the standard-of-care group, the most common toxicities were abdominal pain, nausea, and anemia. A slightly higher proportion of patients in the trametinib group discontinued the drug due to toxicity compared with the standard-of-care group (36% vs 30%), but the there was no difference between the 2 groups in scores on quality-of-life assessments.

Continue to: PARP inhibitors benefit many women with ovarian cancer, but they may hurt others...

PARP inhibitors benefit many women with ovarian cancer, but they may hurt others

Monk BJ, Parkinson C, Lim MC, et al. A randomized, phase III trial to evaluate rucaparib monotherapy as maintenance treatment in patients with newly diagnosed ovarian cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45). J Clin Oncol. 2022;40:3952-3964. doi:10.1200/JCO.22.01003.

Poly(ADP-ribose) polymerase (PARP) inhibitors are a class of oral anticancer agents that target DNA repair. Since the initial FDA approval in 2014 of olaparib for the treatment of patients with recurrent BRCA-mutated ovarian cancer, PARP inhibitors have been approved for maintenance in both the frontline setting and after platinum-sensitive recurrence, and as single-agenttreatment for ovarian cancer with BRCA mutations or evidence of homologous repair deficiency (HRD), a BRCA-like molecular phenotype.⁵ The expanding role for PARP inhibitors in ovarian cancer seemed inexorable.

Restricted prescribing advised

In 2022, we learned that in certain settings, PARP inhibitors may be the wrong choice. Several “Dear Health Care Provider” letters were issued by AstraZeneca, Clovis, and GSK to advise physicians to restrict the prescribing of olaparib, rucaparib, and niraparib.^6,7

AstraZeneca and Clovis issued letters spurred by the final analysis of ARIEL4 and SOLO3 studies, 2 randomized trials that investigated, respectively, rucaparib and olaparib monotherapy compared with chemotherapy in recurrent ovarian cancer.^8,9 In both cases patients randomized to PARP inhibitors may have experienced an overall survival decrement compared with those who received chemotherapy.

At the FDA’s request, Clovis has withdrawn rucaparib as a treatment for patients with recurrent BRCA-mutant ovarian cancer who had received 2 or more lines of chemotherapy, and AstraZeneca withdrew olaparib monotherapy in germline BRCA-mutant patients with recurrent ovarian cancer. Shortly after these withdrawals, GSK also withdrew its indication for niraparib as a treatment for women with HRD, platinum-sensitive ovarian cancer who have received 3 or more prior chemotherapies. Furthermore, based on the final overall survival analysis of the NOVA study, GSK also restricted its indication for niraparib maintenance for recurrent ovarian cancer to patients with germline BRCA mutations, due to evidence of an overall survival detriment in this setting.¹⁰

Positive study results

Fortunately, 2022 was not all bad news for PARP inhibitors in ovarian cancer. In June 2022, the ATHENA-MONO trial, a phase 3 double-blind randomized controlled trial, demonstrated that rucaparib maintenance in patients with newly diagnosed epithelial ovarian cancer was associated with a significantly longer progression-free survival compared with placebo.¹¹ The effect was most pronounced in the BRCA-mutant/HRD population, with a median progression-free survival of 28.7 months in the rucaparib group compared with 11.3 months in the placebo group (HR, 0.47; 95% CI, 0.31–0.72). Thus, rucaparib was added to the list of PARP inhibitors approved for upfront maintenance therapy in epithelial ovarian cancer.

Similarly, the long-term overall survival analysis from the upfront trials SOLO-1 and PAOLA-1 showed an overall survival advantage of PARP inhibitor, compared with placebo, maintenance in patients with BRCA mutations or HRD tumors.^12,13 ●

In 2022, the most significant advances in the treatment of gynecologic cancers were achieved for patients with ovarian cancer. While ovarian cancer continues to carry the worst prognosis of all gynecologic cancers, 5-year relative survival has gradually increased, from 34.4% in 1975 to 52.4% in 2014.¹

In this Update, we highlight the recent advances in our understanding of targeted therapy in ovarian cancer. We review SORAYA, a trial that demonstrated that mirvetuximab soravtansine, an antibody-drug conjugate, has promising efficacy in platinum-resistant ovarian cancers that overexpress folate receptor α. We also spotlight progress in the treatment of low-grade serous ovarian cancer, another notoriously chemotherapy-resistant disease, in GOG 281/LOGS, a phase 2 study of the MEK inhibitor trametinib. Finally, we discuss emerging long-term follow-up data on poly(ADP-ribose) polymerase (PARP) inhibitors, which are helping to refine the role of these groundbreaking drugs.

New drug approved for platinum-resistant epithelial ovarian cancer—the first since 2014

Matulonis UA, Lorusso D, Oaknin A, et al. Efficacy and safety of mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer with high folate receptor alpha expression: results from the SORAYA study. J Clin Oncol. 2023;41:2436-2445. doi:10.1200/JCO.22.01900.

While most patients diagnosed with advanced ovarian cancer will respond to platinum-based chemotherapy, those whose disease recurs eventually develop resistance to platinum agents. Treatment options for platinum-resistant ovarian cancer are limited and prognosis is poor. Most regimens have a response rate of only 10%. Since the approval of bevacizumab combined with chemotherapy in 2014, no new agents have been approved by the US Food and Drug Administration (FDA) for use in platinum-resistant ovarian cancer.

Efficacy shown with mirvetuximab

Recently, Matulonis and colleagues published results of the SORAYA study, a single-arm,phase 2 trial, that examined the efficacy and safety of mirvetuximab soravtansine-gynx among women with platinum-resistant ovarian cancer.² Mirvetuximab is an antibody-drug conjugate composed of an antibody directed at the folate receptor α attached to a cytotoxic microtubule inhibitor.

The study included 106 patients with platinum-resistant ovarian cancer whose tumors expressed folate receptor α at a high level—a feature of approximately 50% of patients screened for the study. Twenty-nine patients experienced a partial response and 5 had a complete response, corresponding to a remarkable objective response rate of 32.4%. The median progression-free survival was 4.3 months.

Like other antibody-drug conjugates, ocular toxicities, including blurred vision (41%) and keratopathy (29%), were common. However, toxicity was manageable and rarely led to drug discontinuation.

Continue to: A novel agent for recurrent low-grade serous ovarian carcinoma...

A novel agent for recurrent low-grade serous ovarian carcinoma

Gershenson DM, Miller A, Brady WE, et al. Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial. Lancet. 2022;399:541-553. doi:10.1016/S0140-6736(21)02175-9.

Low-grade serous carcinoma is a histologic subtype that makes up approximately 5% of all epithelial ovarian cancers.³ Patients with low-grade serous carcinoma are often younger and, because of the indolent nature of the histology, generally have a longer overall survival compared with patients with high-grade serous carcinoma. Unlike high-grade disease, however, low-grade serous carcinoma usually is resistant to chemotherapy, making treatment options limited for patients with advanced and recurrent disease.

Trametinib: A potential option

In an international, randomized, open-label trial (GOG 281/LOGS), Gershenson and colleagues investigated the efficacy of trametinib compared with standard-of-care chemotherapy in patients with recurrent low-grade serous ovarian cancer.⁴ Trametinib, a mitogen-activated protein kinase MEK inhibitor, is a targeted agent that is FDA approved for treatment in BRAF-mutated melanoma, lung, and thyroid cancers.

Patients with recurrent low-grade serous ovarian cancer were randomly assigned to trametinib (n = 130) or 1 of 5 standard-of-care treatment options (n = 130), including both chemotherapy and hormonal treatments. Those assigned to trametinib were significantly less likely to have disease progression (78% vs 89%), with a median progression-free survival of 13 months, compared with7.2 months in controls (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.36–0.64). Additionally, patients who had a radiographic response to trametinib experienced a longer duration of response compared with those who responded to standard-of-care treatment (13.6 months vs 5.9 months).

While there was no statistically significant difference in overall survival (HR, 0.76; 95% CI, 0.51–1.12), crossover to trametinib from the standard-of-care group was allowed and occurred among 68% of patients, which limits the study’s ability to measure differences in overall survival.

Trametinib was well tolerated by patients, but skin rash and anemia followed by hypertension were the most common adverse effects. In the standard-of-care group, the most common toxicities were abdominal pain, nausea, and anemia. A slightly higher proportion of patients in the trametinib group discontinued the drug due to toxicity compared with the standard-of-care group (36% vs 30%), but the there was no difference between the 2 groups in scores on quality-of-life assessments.

Continue to: PARP inhibitors benefit many women with ovarian cancer, but they may hurt others...

PARP inhibitors benefit many women with ovarian cancer, but they may hurt others

Monk BJ, Parkinson C, Lim MC, et al. A randomized, phase III trial to evaluate rucaparib monotherapy as maintenance treatment in patients with newly diagnosed ovarian cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45). J Clin Oncol. 2022;40:3952-3964. doi:10.1200/JCO.22.01003.

Poly(ADP-ribose) polymerase (PARP) inhibitors are a class of oral anticancer agents that target DNA repair. Since the initial FDA approval in 2014 of olaparib for the treatment of patients with recurrent BRCA-mutated ovarian cancer, PARP inhibitors have been approved for maintenance in both the frontline setting and after platinum-sensitive recurrence, and as single-agenttreatment for ovarian cancer with BRCA mutations or evidence of homologous repair deficiency (HRD), a BRCA-like molecular phenotype.⁵ The expanding role for PARP inhibitors in ovarian cancer seemed inexorable.

Restricted prescribing advised

In 2022, we learned that in certain settings, PARP inhibitors may be the wrong choice. Several “Dear Health Care Provider” letters were issued by AstraZeneca, Clovis, and GSK to advise physicians to restrict the prescribing of olaparib, rucaparib, and niraparib.^6,7

AstraZeneca and Clovis issued letters spurred by the final analysis of ARIEL4 and SOLO3 studies, 2 randomized trials that investigated, respectively, rucaparib and olaparib monotherapy compared with chemotherapy in recurrent ovarian cancer.^8,9 In both cases patients randomized to PARP inhibitors may have experienced an overall survival decrement compared with those who received chemotherapy.

At the FDA’s request, Clovis has withdrawn rucaparib as a treatment for patients with recurrent BRCA-mutant ovarian cancer who had received 2 or more lines of chemotherapy, and AstraZeneca withdrew olaparib monotherapy in germline BRCA-mutant patients with recurrent ovarian cancer. Shortly after these withdrawals, GSK also withdrew its indication for niraparib as a treatment for women with HRD, platinum-sensitive ovarian cancer who have received 3 or more prior chemotherapies. Furthermore, based on the final overall survival analysis of the NOVA study, GSK also restricted its indication for niraparib maintenance for recurrent ovarian cancer to patients with germline BRCA mutations, due to evidence of an overall survival detriment in this setting.¹⁰

Positive study results

Fortunately, 2022 was not all bad news for PARP inhibitors in ovarian cancer. In June 2022, the ATHENA-MONO trial, a phase 3 double-blind randomized controlled trial, demonstrated that rucaparib maintenance in patients with newly diagnosed epithelial ovarian cancer was associated with a significantly longer progression-free survival compared with placebo.¹¹ The effect was most pronounced in the BRCA-mutant/HRD population, with a median progression-free survival of 28.7 months in the rucaparib group compared with 11.3 months in the placebo group (HR, 0.47; 95% CI, 0.31–0.72). Thus, rucaparib was added to the list of PARP inhibitors approved for upfront maintenance therapy in epithelial ovarian cancer.

Similarly, the long-term overall survival analysis from the upfront trials SOLO-1 and PAOLA-1 showed an overall survival advantage of PARP inhibitor, compared with placebo, maintenance in patients with BRCA mutations or HRD tumors.^12,13 ●

In 2022, the most significant advances in the treatment of gynecologic cancers were achieved for patients with ovarian cancer. While ovarian cancer continues to carry the worst prognosis of all gynecologic cancers, 5-year relative survival has gradually increased, from 34.4% in 1975 to 52.4% in 2014.¹

In this Update, we highlight the recent advances in our understanding of targeted therapy in ovarian cancer. We review SORAYA, a trial that demonstrated that mirvetuximab soravtansine, an antibody-drug conjugate, has promising efficacy in platinum-resistant ovarian cancers that overexpress folate receptor α. We also spotlight progress in the treatment of low-grade serous ovarian cancer, another notoriously chemotherapy-resistant disease, in GOG 281/LOGS, a phase 2 study of the MEK inhibitor trametinib. Finally, we discuss emerging long-term follow-up data on poly(ADP-ribose) polymerase (PARP) inhibitors, which are helping to refine the role of these groundbreaking drugs.

New drug approved for platinum-resistant epithelial ovarian cancer—the first since 2014

Matulonis UA, Lorusso D, Oaknin A, et al. Efficacy and safety of mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer with high folate receptor alpha expression: results from the SORAYA study. J Clin Oncol. 2023;41:2436-2445. doi:10.1200/JCO.22.01900.

While most patients diagnosed with advanced ovarian cancer will respond to platinum-based chemotherapy, those whose disease recurs eventually develop resistance to platinum agents. Treatment options for platinum-resistant ovarian cancer are limited and prognosis is poor. Most regimens have a response rate of only 10%. Since the approval of bevacizumab combined with chemotherapy in 2014, no new agents have been approved by the US Food and Drug Administration (FDA) for use in platinum-resistant ovarian cancer.

Efficacy shown with mirvetuximab

Recently, Matulonis and colleagues published results of the SORAYA study, a single-arm,phase 2 trial, that examined the efficacy and safety of mirvetuximab soravtansine-gynx among women with platinum-resistant ovarian cancer.² Mirvetuximab is an antibody-drug conjugate composed of an antibody directed at the folate receptor α attached to a cytotoxic microtubule inhibitor.

The study included 106 patients with platinum-resistant ovarian cancer whose tumors expressed folate receptor α at a high level—a feature of approximately 50% of patients screened for the study. Twenty-nine patients experienced a partial response and 5 had a complete response, corresponding to a remarkable objective response rate of 32.4%. The median progression-free survival was 4.3 months.

Like other antibody-drug conjugates, ocular toxicities, including blurred vision (41%) and keratopathy (29%), were common. However, toxicity was manageable and rarely led to drug discontinuation.

Continue to: A novel agent for recurrent low-grade serous ovarian carcinoma...

A novel agent for recurrent low-grade serous ovarian carcinoma

Gershenson DM, Miller A, Brady WE, et al. Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial. Lancet. 2022;399:541-553. doi:10.1016/S0140-6736(21)02175-9.

Low-grade serous carcinoma is a histologic subtype that makes up approximately 5% of all epithelial ovarian cancers.³ Patients with low-grade serous carcinoma are often younger and, because of the indolent nature of the histology, generally have a longer overall survival compared with patients with high-grade serous carcinoma. Unlike high-grade disease, however, low-grade serous carcinoma usually is resistant to chemotherapy, making treatment options limited for patients with advanced and recurrent disease.

Trametinib: A potential option

In an international, randomized, open-label trial (GOG 281/LOGS), Gershenson and colleagues investigated the efficacy of trametinib compared with standard-of-care chemotherapy in patients with recurrent low-grade serous ovarian cancer.⁴ Trametinib, a mitogen-activated protein kinase MEK inhibitor, is a targeted agent that is FDA approved for treatment in BRAF-mutated melanoma, lung, and thyroid cancers.

Patients with recurrent low-grade serous ovarian cancer were randomly assigned to trametinib (n = 130) or 1 of 5 standard-of-care treatment options (n = 130), including both chemotherapy and hormonal treatments. Those assigned to trametinib were significantly less likely to have disease progression (78% vs 89%), with a median progression-free survival of 13 months, compared with7.2 months in controls (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.36–0.64). Additionally, patients who had a radiographic response to trametinib experienced a longer duration of response compared with those who responded to standard-of-care treatment (13.6 months vs 5.9 months).

While there was no statistically significant difference in overall survival (HR, 0.76; 95% CI, 0.51–1.12), crossover to trametinib from the standard-of-care group was allowed and occurred among 68% of patients, which limits the study’s ability to measure differences in overall survival.

Trametinib was well tolerated by patients, but skin rash and anemia followed by hypertension were the most common adverse effects. In the standard-of-care group, the most common toxicities were abdominal pain, nausea, and anemia. A slightly higher proportion of patients in the trametinib group discontinued the drug due to toxicity compared with the standard-of-care group (36% vs 30%), but the there was no difference between the 2 groups in scores on quality-of-life assessments.

Continue to: PARP inhibitors benefit many women with ovarian cancer, but they may hurt others...

PARP inhibitors benefit many women with ovarian cancer, but they may hurt others

Monk BJ, Parkinson C, Lim MC, et al. A randomized, phase III trial to evaluate rucaparib monotherapy as maintenance treatment in patients with newly diagnosed ovarian cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45). J Clin Oncol. 2022;40:3952-3964. doi:10.1200/JCO.22.01003.

Poly(ADP-ribose) polymerase (PARP) inhibitors are a class of oral anticancer agents that target DNA repair. Since the initial FDA approval in 2014 of olaparib for the treatment of patients with recurrent BRCA-mutated ovarian cancer, PARP inhibitors have been approved for maintenance in both the frontline setting and after platinum-sensitive recurrence, and as single-agenttreatment for ovarian cancer with BRCA mutations or evidence of homologous repair deficiency (HRD), a BRCA-like molecular phenotype.⁵ The expanding role for PARP inhibitors in ovarian cancer seemed inexorable.

Restricted prescribing advised

In 2022, we learned that in certain settings, PARP inhibitors may be the wrong choice. Several “Dear Health Care Provider” letters were issued by AstraZeneca, Clovis, and GSK to advise physicians to restrict the prescribing of olaparib, rucaparib, and niraparib.^6,7

AstraZeneca and Clovis issued letters spurred by the final analysis of ARIEL4 and SOLO3 studies, 2 randomized trials that investigated, respectively, rucaparib and olaparib monotherapy compared with chemotherapy in recurrent ovarian cancer.^8,9 In both cases patients randomized to PARP inhibitors may have experienced an overall survival decrement compared with those who received chemotherapy.

At the FDA’s request, Clovis has withdrawn rucaparib as a treatment for patients with recurrent BRCA-mutant ovarian cancer who had received 2 or more lines of chemotherapy, and AstraZeneca withdrew olaparib monotherapy in germline BRCA-mutant patients with recurrent ovarian cancer. Shortly after these withdrawals, GSK also withdrew its indication for niraparib as a treatment for women with HRD, platinum-sensitive ovarian cancer who have received 3 or more prior chemotherapies. Furthermore, based on the final overall survival analysis of the NOVA study, GSK also restricted its indication for niraparib maintenance for recurrent ovarian cancer to patients with germline BRCA mutations, due to evidence of an overall survival detriment in this setting.¹⁰

Positive study results

Fortunately, 2022 was not all bad news for PARP inhibitors in ovarian cancer. In June 2022, the ATHENA-MONO trial, a phase 3 double-blind randomized controlled trial, demonstrated that rucaparib maintenance in patients with newly diagnosed epithelial ovarian cancer was associated with a significantly longer progression-free survival compared with placebo.¹¹ The effect was most pronounced in the BRCA-mutant/HRD population, with a median progression-free survival of 28.7 months in the rucaparib group compared with 11.3 months in the placebo group (HR, 0.47; 95% CI, 0.31–0.72). Thus, rucaparib was added to the list of PARP inhibitors approved for upfront maintenance therapy in epithelial ovarian cancer.

Similarly, the long-term overall survival analysis from the upfront trials SOLO-1 and PAOLA-1 showed an overall survival advantage of PARP inhibitor, compared with placebo, maintenance in patients with BRCA mutations or HRD tumors.^12,13 ●

Key clinical point: Patients with rheumatoid arthritis (RA) who were ≥65 years old had a significantly increased risk of developing sarcopenia, particularly if they were men with poor nutritional status and long-standing disease.

Major finding: Sarcopenia was diagnosed in a higher proportion of patients with RA vs control individuals without RA (15.8% vs 3.9%; P = .014). Male sex (P = .042), longer disease duration (P = .012), and poorer nutritional status (P = .042) were significant risk factors for the development of sarcopenia in older patients with RA.

Study details: Findings are from a cross-sectional study including 76 patients age ≥ 65 years with RA and 76 age- and sex-matched control individuals without RA.

Disclosures: This study was funded by Redes de Investigación Cooperativa Orientadas a Resultados en Salud, Spain, and other sources. The authors declared no conflicts of interest.

Source: Cano-García L et al. Sarcopenia and nutrition in elderly rheumatoid arthritis patients: A cross-sectional study to determine prevalence and risk factors. Nutrients. 2023;15:2440 (May 24). doi: 10.3390/nu15112440

Key clinical point: Patients with rheumatoid arthritis (RA) who were ≥65 years old had a significantly increased risk of developing sarcopenia, particularly if they were men with poor nutritional status and long-standing disease.

Major finding: Sarcopenia was diagnosed in a higher proportion of patients with RA vs control individuals without RA (15.8% vs 3.9%; P = .014). Male sex (P = .042), longer disease duration (P = .012), and poorer nutritional status (P = .042) were significant risk factors for the development of sarcopenia in older patients with RA.

Study details: Findings are from a cross-sectional study including 76 patients age ≥ 65 years with RA and 76 age- and sex-matched control individuals without RA.

Disclosures: This study was funded by Redes de Investigación Cooperativa Orientadas a Resultados en Salud, Spain, and other sources. The authors declared no conflicts of interest.

Source: Cano-García L et al. Sarcopenia and nutrition in elderly rheumatoid arthritis patients: A cross-sectional study to determine prevalence and risk factors. Nutrients. 2023;15:2440 (May 24). doi: 10.3390/nu15112440

Key clinical point: Patients with rheumatoid arthritis (RA) who were ≥65 years old had a significantly increased risk of developing sarcopenia, particularly if they were men with poor nutritional status and long-standing disease.

Major finding: Sarcopenia was diagnosed in a higher proportion of patients with RA vs control individuals without RA (15.8% vs 3.9%; P = .014). Male sex (P = .042), longer disease duration (P = .012), and poorer nutritional status (P = .042) were significant risk factors for the development of sarcopenia in older patients with RA.

Study details: Findings are from a cross-sectional study including 76 patients age ≥ 65 years with RA and 76 age- and sex-matched control individuals without RA.

Disclosures: This study was funded by Redes de Investigación Cooperativa Orientadas a Resultados en Salud, Spain, and other sources. The authors declared no conflicts of interest.

Source: Cano-García L et al. Sarcopenia and nutrition in elderly rheumatoid arthritis patients: A cross-sectional study to determine prevalence and risk factors. Nutrients. 2023;15:2440 (May 24). doi: 10.3390/nu15112440

Key clinical point: Intensive treatment more effectively suppressed joint damage progression than the current treatment in patients with rheumatoid arthritis (RA) who showed joint damage progression and had low disease activity (LDA) or were in remission.

Major finding: At 1 year of treatment, intensive vs current treatment was associated with a smaller change in the van der Heijde modified total Sharp score (ΔTSS; 0.67 vs 1.79; P < .001) and joint space narrowing scores (0.57 vs 1.41; P < .001) and a larger proportion of patients achieved a ΔTSS of ≤0.5 (66.7% vs 32.4%; P = .010).

Study details: This retrospective study included 89 patients with RA in remission or with LDA who showed joint damage progression and were assigned to either receive intensive treatment or continue the current treatment.

Disclosures: This study did not declare the funding source. T Mochizuki, K Yano, and K Ikari declared receiving lecture honoraria from various sources. The other authors declared no conflicts of interest.

Source: Mochizuki T et al. Intensive treatment for the progression of joint damage in rheumatoid arthritis patients with low disease activity or remission. Mod Rheumatol. 2023 (Jun 2). doi: 10.1093/mr/road041

Key clinical point: Intensive treatment more effectively suppressed joint damage progression than the current treatment in patients with rheumatoid arthritis (RA) who showed joint damage progression and had low disease activity (LDA) or were in remission.

Major finding: At 1 year of treatment, intensive vs current treatment was associated with a smaller change in the van der Heijde modified total Sharp score (ΔTSS; 0.67 vs 1.79; P < .001) and joint space narrowing scores (0.57 vs 1.41; P < .001) and a larger proportion of patients achieved a ΔTSS of ≤0.5 (66.7% vs 32.4%; P = .010).

Study details: This retrospective study included 89 patients with RA in remission or with LDA who showed joint damage progression and were assigned to either receive intensive treatment or continue the current treatment.

Disclosures: This study did not declare the funding source. T Mochizuki, K Yano, and K Ikari declared receiving lecture honoraria from various sources. The other authors declared no conflicts of interest.

Source: Mochizuki T et al. Intensive treatment for the progression of joint damage in rheumatoid arthritis patients with low disease activity or remission. Mod Rheumatol. 2023 (Jun 2). doi: 10.1093/mr/road041

Key clinical point: Intensive treatment more effectively suppressed joint damage progression than the current treatment in patients with rheumatoid arthritis (RA) who showed joint damage progression and had low disease activity (LDA) or were in remission.

Major finding: At 1 year of treatment, intensive vs current treatment was associated with a smaller change in the van der Heijde modified total Sharp score (ΔTSS; 0.67 vs 1.79; P < .001) and joint space narrowing scores (0.57 vs 1.41; P < .001) and a larger proportion of patients achieved a ΔTSS of ≤0.5 (66.7% vs 32.4%; P = .010).

Study details: This retrospective study included 89 patients with RA in remission or with LDA who showed joint damage progression and were assigned to either receive intensive treatment or continue the current treatment.

Disclosures: This study did not declare the funding source. T Mochizuki, K Yano, and K Ikari declared receiving lecture honoraria from various sources. The other authors declared no conflicts of interest.

Source: Mochizuki T et al. Intensive treatment for the progression of joint damage in rheumatoid arthritis patients with low disease activity or remission. Mod Rheumatol. 2023 (Jun 2). doi: 10.1093/mr/road041

Key clinical point: Ultrasound detected subclinical inflammation in the wrist joints of most patients with rheumatoid arthritis (RA) in clinical remission or with lower disease activity, with the risk for subclinical inflammation being lower among those using biologic therapy.

Major finding: Overall, subclinical inflammation was detected in 57.4% of the patients in complete remission or with lower disease activity. Factors negatively associated with subclinical inflammation included the use of biologic therapy (odds ratio [OR] 0.59; P = .001), methotrexate (OR 0.83; P = .020), and glucocorticoids (OR 0.60; P = .001) and alcohol consumption (OR 0.55; P = .006).

Study details: This cross-sectional study included 1248 patients with RA who underwent gray scale and power Doppler ultrasound assessments of the dorsal radiolunate joints of both wrists.

Disclosures: This study was supported by the Kaohsiung Chang Gung Memorial Hospital, Taiwan, and other sources. The authors declared no conflicts of interest.

Source: Wang YW et al. Factors associated with subclinical inflammation of wrist joints in rheumatoid arthritis patients with low or no disease activity—A RA ultrasound registry study. BMC Musculoskelet Disord. 2023;24:438 (May 30). doi: 10.1186/s12891-023-06521-8

Key clinical point: Ultrasound detected subclinical inflammation in the wrist joints of most patients with rheumatoid arthritis (RA) in clinical remission or with lower disease activity, with the risk for subclinical inflammation being lower among those using biologic therapy.

Major finding: Overall, subclinical inflammation was detected in 57.4% of the patients in complete remission or with lower disease activity. Factors negatively associated with subclinical inflammation included the use of biologic therapy (odds ratio [OR] 0.59; P = .001), methotrexate (OR 0.83; P = .020), and glucocorticoids (OR 0.60; P = .001) and alcohol consumption (OR 0.55; P = .006).

Study details: This cross-sectional study included 1248 patients with RA who underwent gray scale and power Doppler ultrasound assessments of the dorsal radiolunate joints of both wrists.

Disclosures: This study was supported by the Kaohsiung Chang Gung Memorial Hospital, Taiwan, and other sources. The authors declared no conflicts of interest.

Source: Wang YW et al. Factors associated with subclinical inflammation of wrist joints in rheumatoid arthritis patients with low or no disease activity—A RA ultrasound registry study. BMC Musculoskelet Disord. 2023;24:438 (May 30). doi: 10.1186/s12891-023-06521-8

Key clinical point: Ultrasound detected subclinical inflammation in the wrist joints of most patients with rheumatoid arthritis (RA) in clinical remission or with lower disease activity, with the risk for subclinical inflammation being lower among those using biologic therapy.

Major finding: Overall, subclinical inflammation was detected in 57.4% of the patients in complete remission or with lower disease activity. Factors negatively associated with subclinical inflammation included the use of biologic therapy (odds ratio [OR] 0.59; P = .001), methotrexate (OR 0.83; P = .020), and glucocorticoids (OR 0.60; P = .001) and alcohol consumption (OR 0.55; P = .006).

Study details: This cross-sectional study included 1248 patients with RA who underwent gray scale and power Doppler ultrasound assessments of the dorsal radiolunate joints of both wrists.

Disclosures: This study was supported by the Kaohsiung Chang Gung Memorial Hospital, Taiwan, and other sources. The authors declared no conflicts of interest.

Source: Wang YW et al. Factors associated with subclinical inflammation of wrist joints in rheumatoid arthritis patients with low or no disease activity—A RA ultrasound registry study. BMC Musculoskelet Disord. 2023;24:438 (May 30). doi: 10.1186/s12891-023-06521-8

Key clinical point: Depression significantly predicted death in patients with incident rheumatoid arthritis (RA), but with a strength similar to that in matched comparator individuals without RA.

Major finding: The risk for all-cause mortality was >3-fold higher (adjusted hazard rate ratio [aHRR] 3.15; 95% CI 2.62-3.79) in patients with RA with vs without depression, with the risk being higher among patients age < 55 years compared with other age groups (aHRR 8.13; 95% CI 3.89-17.02). In addition, depression predicted all-cause mortality with similar strength in comparator individuals without RA (aHRR 3.77; 95% CI 3.48-4.08).

Study details: This study included 11,071 patients with incident RA and 55,355 matched comparator individuals without RA from the general population.

Disclosures: This study was supported by the Danish Rheumatism Association. The authors declared no conflicts of interest.

Source: Pedersen JK et al. Mortality in patients with incident rheumatoid arthritis and depression: A Danish cohort study of 11,071 patients and 55,355 comparators. Rheumatology (Oxford). 2023 (May 30). doi: 10.1093/rheumatology/kead259

Key clinical point: Depression significantly predicted death in patients with incident rheumatoid arthritis (RA), but with a strength similar to that in matched comparator individuals without RA.

Major finding: The risk for all-cause mortality was >3-fold higher (adjusted hazard rate ratio [aHRR] 3.15; 95% CI 2.62-3.79) in patients with RA with vs without depression, with the risk being higher among patients age < 55 years compared with other age groups (aHRR 8.13; 95% CI 3.89-17.02). In addition, depression predicted all-cause mortality with similar strength in comparator individuals without RA (aHRR 3.77; 95% CI 3.48-4.08).

Study details: This study included 11,071 patients with incident RA and 55,355 matched comparator individuals without RA from the general population.

Disclosures: This study was supported by the Danish Rheumatism Association. The authors declared no conflicts of interest.

Source: Pedersen JK et al. Mortality in patients with incident rheumatoid arthritis and depression: A Danish cohort study of 11,071 patients and 55,355 comparators. Rheumatology (Oxford). 2023 (May 30). doi: 10.1093/rheumatology/kead259

Key clinical point: Depression significantly predicted death in patients with incident rheumatoid arthritis (RA), but with a strength similar to that in matched comparator individuals without RA.

Major finding: The risk for all-cause mortality was >3-fold higher (adjusted hazard rate ratio [aHRR] 3.15; 95% CI 2.62-3.79) in patients with RA with vs without depression, with the risk being higher among patients age < 55 years compared with other age groups (aHRR 8.13; 95% CI 3.89-17.02). In addition, depression predicted all-cause mortality with similar strength in comparator individuals without RA (aHRR 3.77; 95% CI 3.48-4.08).

Study details: This study included 11,071 patients with incident RA and 55,355 matched comparator individuals without RA from the general population.

Disclosures: This study was supported by the Danish Rheumatism Association. The authors declared no conflicts of interest.

Source: Pedersen JK et al. Mortality in patients with incident rheumatoid arthritis and depression: A Danish cohort study of 11,071 patients and 55,355 comparators. Rheumatology (Oxford). 2023 (May 30). doi: 10.1093/rheumatology/kead259

Key clinical point: Perioperative use of Janus kinase inhibitors (JAKi) seemed safe in patients with rheumatoid arthritis (RA) undergoing orthopedic procedures; however, the benefits of withholding JAKi to prevent postoperative complications should be balanced against the risk for a flare-up in disease activity.

Major finding: Overall, 20 patients undergoing 31 orthopedic procedures continued JAKi perioperatively, whereas 16 patients undergoing 18 procedures discontinued JAKi perioperatively by ≥1 dose for various reasons. No surgical site infections were reported during ≥90 days of follow-up. Disease flare-up was observed in 2 patients who discontinued JAKi for 3 and 14 days, respectively; however, those who discontinued JAKi for ≤1 day showed no flare-up.

Study details: This retrospective study included 32 patients with RA who had disease under control with JAKi and underwent a total of 49 orthopedic procedures.

Disclosures: This study did not receive any funding, grants, or other support. K Nishida declared receiving research grants or speaker fees from various sources.

Source: Nishida K et al. Influence of Janus kinase inhibitors on early postoperative complications in patients with rheumatoid arthritis undergoing orthopaedic surgeries. Mod Rheumatol. 2023 (Jun 3). doi: 10.1093/mr/road047

Key clinical point: Perioperative use of Janus kinase inhibitors (JAKi) seemed safe in patients with rheumatoid arthritis (RA) undergoing orthopedic procedures; however, the benefits of withholding JAKi to prevent postoperative complications should be balanced against the risk for a flare-up in disease activity.

Major finding: Overall, 20 patients undergoing 31 orthopedic procedures continued JAKi perioperatively, whereas 16 patients undergoing 18 procedures discontinued JAKi perioperatively by ≥1 dose for various reasons. No surgical site infections were reported during ≥90 days of follow-up. Disease flare-up was observed in 2 patients who discontinued JAKi for 3 and 14 days, respectively; however, those who discontinued JAKi for ≤1 day showed no flare-up.

Study details: This retrospective study included 32 patients with RA who had disease under control with JAKi and underwent a total of 49 orthopedic procedures.

Disclosures: This study did not receive any funding, grants, or other support. K Nishida declared receiving research grants or speaker fees from various sources.

Source: Nishida K et al. Influence of Janus kinase inhibitors on early postoperative complications in patients with rheumatoid arthritis undergoing orthopaedic surgeries. Mod Rheumatol. 2023 (Jun 3). doi: 10.1093/mr/road047

Key clinical point: Perioperative use of Janus kinase inhibitors (JAKi) seemed safe in patients with rheumatoid arthritis (RA) undergoing orthopedic procedures; however, the benefits of withholding JAKi to prevent postoperative complications should be balanced against the risk for a flare-up in disease activity.

Major finding: Overall, 20 patients undergoing 31 orthopedic procedures continued JAKi perioperatively, whereas 16 patients undergoing 18 procedures discontinued JAKi perioperatively by ≥1 dose for various reasons. No surgical site infections were reported during ≥90 days of follow-up. Disease flare-up was observed in 2 patients who discontinued JAKi for 3 and 14 days, respectively; however, those who discontinued JAKi for ≤1 day showed no flare-up.

Study details: This retrospective study included 32 patients with RA who had disease under control with JAKi and underwent a total of 49 orthopedic procedures.

Disclosures: This study did not receive any funding, grants, or other support. K Nishida declared receiving research grants or speaker fees from various sources.

Source: Nishida K et al. Influence of Janus kinase inhibitors on early postoperative complications in patients with rheumatoid arthritis undergoing orthopaedic surgeries. Mod Rheumatol. 2023 (Jun 3). doi: 10.1093/mr/road047