Clinical Edge Journal Scan

Key clinical point: Nivolumab plus docetaxel shows good response in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC).

Major finding: The confirmed overall response rate was 40%. The median time to objective response was 2 months, and the median response duration was 7 months. The confirmed prostate-specific antigen (PSA) 50-response rate (50% or higher decline in PSA) was 46.9%.

Study details: A phase 2, nonrandomized CheckMate 9KD trial of 84 patients with chemotherapy-naive mCRPC who received androgen deprivation therapy and ≤2 prior novel hormonal therapies and were treated with nivolumab and docetaxel with prednisone followed by nivolumab maintenance for ≤2 years.

Disclosures: This work was supported by Bristol Myers Squibb (BMS). The authors reported receiving consulting/advisory/speaker fees, travel accommodations, expenses, honoraria, and research funding from various sources. Some authors were employed by/owned stocks in BMS.

Source: Fizazi K et al. Eur J Cancer. 2021 Nov 18. doi: 10.1016/j.ejca.2021.09.043.

Key clinical point: Nivolumab plus docetaxel shows good response in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC).

Major finding: The confirmed overall response rate was 40%. The median time to objective response was 2 months, and the median response duration was 7 months. The confirmed prostate-specific antigen (PSA) 50-response rate (50% or higher decline in PSA) was 46.9%.

Study details: A phase 2, nonrandomized CheckMate 9KD trial of 84 patients with chemotherapy-naive mCRPC who received androgen deprivation therapy and ≤2 prior novel hormonal therapies and were treated with nivolumab and docetaxel with prednisone followed by nivolumab maintenance for ≤2 years.

Disclosures: This work was supported by Bristol Myers Squibb (BMS). The authors reported receiving consulting/advisory/speaker fees, travel accommodations, expenses, honoraria, and research funding from various sources. Some authors were employed by/owned stocks in BMS.

Source: Fizazi K et al. Eur J Cancer. 2021 Nov 18. doi: 10.1016/j.ejca.2021.09.043.

Key clinical point: Nivolumab plus docetaxel shows good response in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC).

Major finding: The confirmed overall response rate was 40%. The median time to objective response was 2 months, and the median response duration was 7 months. The confirmed prostate-specific antigen (PSA) 50-response rate (50% or higher decline in PSA) was 46.9%.

Study details: A phase 2, nonrandomized CheckMate 9KD trial of 84 patients with chemotherapy-naive mCRPC who received androgen deprivation therapy and ≤2 prior novel hormonal therapies and were treated with nivolumab and docetaxel with prednisone followed by nivolumab maintenance for ≤2 years.

Disclosures: This work was supported by Bristol Myers Squibb (BMS). The authors reported receiving consulting/advisory/speaker fees, travel accommodations, expenses, honoraria, and research funding from various sources. Some authors were employed by/owned stocks in BMS.

Source: Fizazi K et al. Eur J Cancer. 2021 Nov 18. doi: 10.1016/j.ejca.2021.09.043.

This month’s round up of clinical studies is a fitting end to 2021 – they provide a close look at the intersection between pancreatic pathology and SARS CoV-2 infection.  The first study, out of the UK, speculated that SARS CoV-2 virus may be associated with development of idiopathic pancreatitis.¹  They followed 1,476 patients with acute pancreatitis for 12 months (118 of whom were positive for SARS CoV-2, and 1,358 of whom were negative for the virus).  The patients underwent magnetic resonance cholangiopancreatography, endoscopic ultrasound, or biochemical investigations to exclude other causes of pancreatitis.  Remarkably, as the paper states, “Patients who were SARS-CoV-2 positive were more likely to have idiopathic acute pancreatitis (AP, 34.7% vs 13.9%, P < .001) with over five times increased risk after adjusting for age, smoking status, body mass index and ethnicity (odds ration [OR] 5.34, P < .001).”  

Secondarily, the authors aimed to determine if SARS CoV-2 infection would increase risk for diabetes mellitus (DM) and pancreatic exocrine insufficiency (PEI).  Notably, SARS-CoV-2 did not increase the risk of DM (2.3% vs 2.5%, OR 0.61, P = .541) or PEI (OR 1.11, P = .828) (P > .05).  The relationship between pancreatitis and SARS CoV-2 infection is indeed an important one – the authors point out that autopsy studies have demonstrated the presence of virus in pancreatic tissue.  There is clear mechanistic reason for trophism as ACE 2 receptors are found on exocrine and endocrine cells of the pancreas.  

Another study, out of Hubei Province, China, looked at the association of elevated serum amylase (ESA) with mortality and other adverse outcomes  in hospitalized patients with COVID-19.²  Their retrospective study included 1,515 inpatients with COVID-19.  Overall, 196 patients had ESA, of which 9.7% had an ESA of >3 times the upper limit of normal (ULN).  Somewhat not unexpectedly, hyperamylasemia was independently associated with mortality (1-3-times ULN [1-3 ULN]: hazard ratio [HR] 1.63; P = .034; >3-fold ULN [>3 ULN]: HR 8.90; P < .001) and adverse outcomes, such as sepsis (1-3 ULN: odds ratio [OR] 1.15; >3 ULN: OR 1.87), disseminated intravascular coagulation (1-3 ULN: OR 1.13; >3 ULN: OR 1.65), cardiac injury (1-3 ULN: OR 1.24; >3 ULN: OR 1.71), acute respiratory distress syndrome (1-3 ULN: OR 1.21; >3 ULN: OR 1.62), and acute kidney injury (1-3 ULN: OR 1.24; >3 ULN: OR 1.79).  The authors conclude that, “​​Since early intervention might change the outcome, serum amylase should be monitored dynamically during hospitalization.”  It appears to be unclear what would be practice changing, assuming patients would already be receiving appropriate resuscitation.  

More interesting, perhaps, is the question of whether or not the pancreas is merely a bystander casualty or an active protagonist in the role of sepsis and disease severity in highly morbid diseases, such as COVID-19.  

References

1.           Nayar M et al. SARS-CoV-2 infection is associated with an increased risk of idiopathic acute pancreatitis but not pancreatic exocrine insufficiency or diabetes: long-term results of the COVIDPAN study. Gut 2021(Nov 11).

2.           Li G et al. Serum amylase elevation is associated with adverse clinical outcomes in patients with coronavirus disease 2019. Aging (Albany NY) 2021;13(20):23442–58 (Oct 2021).

This month’s round up of clinical studies is a fitting end to 2021 – they provide a close look at the intersection between pancreatic pathology and SARS CoV-2 infection.  The first study, out of the UK, speculated that SARS CoV-2 virus may be associated with development of idiopathic pancreatitis.¹  They followed 1,476 patients with acute pancreatitis for 12 months (118 of whom were positive for SARS CoV-2, and 1,358 of whom were negative for the virus).  The patients underwent magnetic resonance cholangiopancreatography, endoscopic ultrasound, or biochemical investigations to exclude other causes of pancreatitis.  Remarkably, as the paper states, “Patients who were SARS-CoV-2 positive were more likely to have idiopathic acute pancreatitis (AP, 34.7% vs 13.9%, P < .001) with over five times increased risk after adjusting for age, smoking status, body mass index and ethnicity (odds ration [OR] 5.34, P < .001).”  

Secondarily, the authors aimed to determine if SARS CoV-2 infection would increase risk for diabetes mellitus (DM) and pancreatic exocrine insufficiency (PEI).  Notably, SARS-CoV-2 did not increase the risk of DM (2.3% vs 2.5%, OR 0.61, P = .541) or PEI (OR 1.11, P = .828) (P > .05).  The relationship between pancreatitis and SARS CoV-2 infection is indeed an important one – the authors point out that autopsy studies have demonstrated the presence of virus in pancreatic tissue.  There is clear mechanistic reason for trophism as ACE 2 receptors are found on exocrine and endocrine cells of the pancreas.  

Another study, out of Hubei Province, China, looked at the association of elevated serum amylase (ESA) with mortality and other adverse outcomes  in hospitalized patients with COVID-19.²  Their retrospective study included 1,515 inpatients with COVID-19.  Overall, 196 patients had ESA, of which 9.7% had an ESA of >3 times the upper limit of normal (ULN).  Somewhat not unexpectedly, hyperamylasemia was independently associated with mortality (1-3-times ULN [1-3 ULN]: hazard ratio [HR] 1.63; P = .034; >3-fold ULN [>3 ULN]: HR 8.90; P < .001) and adverse outcomes, such as sepsis (1-3 ULN: odds ratio [OR] 1.15; >3 ULN: OR 1.87), disseminated intravascular coagulation (1-3 ULN: OR 1.13; >3 ULN: OR 1.65), cardiac injury (1-3 ULN: OR 1.24; >3 ULN: OR 1.71), acute respiratory distress syndrome (1-3 ULN: OR 1.21; >3 ULN: OR 1.62), and acute kidney injury (1-3 ULN: OR 1.24; >3 ULN: OR 1.79).  The authors conclude that, “​​Since early intervention might change the outcome, serum amylase should be monitored dynamically during hospitalization.”  It appears to be unclear what would be practice changing, assuming patients would already be receiving appropriate resuscitation.  

More interesting, perhaps, is the question of whether or not the pancreas is merely a bystander casualty or an active protagonist in the role of sepsis and disease severity in highly morbid diseases, such as COVID-19.  

References

1.           Nayar M et al. SARS-CoV-2 infection is associated with an increased risk of idiopathic acute pancreatitis but not pancreatic exocrine insufficiency or diabetes: long-term results of the COVIDPAN study. Gut 2021(Nov 11).

2.           Li G et al. Serum amylase elevation is associated with adverse clinical outcomes in patients with coronavirus disease 2019. Aging (Albany NY) 2021;13(20):23442–58 (Oct 2021).

This month’s round up of clinical studies is a fitting end to 2021 – they provide a close look at the intersection between pancreatic pathology and SARS CoV-2 infection.  The first study, out of the UK, speculated that SARS CoV-2 virus may be associated with development of idiopathic pancreatitis.¹  They followed 1,476 patients with acute pancreatitis for 12 months (118 of whom were positive for SARS CoV-2, and 1,358 of whom were negative for the virus).  The patients underwent magnetic resonance cholangiopancreatography, endoscopic ultrasound, or biochemical investigations to exclude other causes of pancreatitis.  Remarkably, as the paper states, “Patients who were SARS-CoV-2 positive were more likely to have idiopathic acute pancreatitis (AP, 34.7% vs 13.9%, P < .001) with over five times increased risk after adjusting for age, smoking status, body mass index and ethnicity (odds ration [OR] 5.34, P < .001).”  

Secondarily, the authors aimed to determine if SARS CoV-2 infection would increase risk for diabetes mellitus (DM) and pancreatic exocrine insufficiency (PEI).  Notably, SARS-CoV-2 did not increase the risk of DM (2.3% vs 2.5%, OR 0.61, P = .541) or PEI (OR 1.11, P = .828) (P > .05).  The relationship between pancreatitis and SARS CoV-2 infection is indeed an important one – the authors point out that autopsy studies have demonstrated the presence of virus in pancreatic tissue.  There is clear mechanistic reason for trophism as ACE 2 receptors are found on exocrine and endocrine cells of the pancreas.  

Another study, out of Hubei Province, China, looked at the association of elevated serum amylase (ESA) with mortality and other adverse outcomes  in hospitalized patients with COVID-19.²  Their retrospective study included 1,515 inpatients with COVID-19.  Overall, 196 patients had ESA, of which 9.7% had an ESA of >3 times the upper limit of normal (ULN).  Somewhat not unexpectedly, hyperamylasemia was independently associated with mortality (1-3-times ULN [1-3 ULN]: hazard ratio [HR] 1.63; P = .034; >3-fold ULN [>3 ULN]: HR 8.90; P < .001) and adverse outcomes, such as sepsis (1-3 ULN: odds ratio [OR] 1.15; >3 ULN: OR 1.87), disseminated intravascular coagulation (1-3 ULN: OR 1.13; >3 ULN: OR 1.65), cardiac injury (1-3 ULN: OR 1.24; >3 ULN: OR 1.71), acute respiratory distress syndrome (1-3 ULN: OR 1.21; >3 ULN: OR 1.62), and acute kidney injury (1-3 ULN: OR 1.24; >3 ULN: OR 1.79).  The authors conclude that, “​​Since early intervention might change the outcome, serum amylase should be monitored dynamically during hospitalization.”  It appears to be unclear what would be practice changing, assuming patients would already be receiving appropriate resuscitation.  

More interesting, perhaps, is the question of whether or not the pancreas is merely a bystander casualty or an active protagonist in the role of sepsis and disease severity in highly morbid diseases, such as COVID-19.  

References

1.           Nayar M et al. SARS-CoV-2 infection is associated with an increased risk of idiopathic acute pancreatitis but not pancreatic exocrine insufficiency or diabetes: long-term results of the COVIDPAN study. Gut 2021(Nov 11).

2.           Li G et al. Serum amylase elevation is associated with adverse clinical outcomes in patients with coronavirus disease 2019. Aging (Albany NY) 2021;13(20):23442–58 (Oct 2021).

This month, the phase II randomized study of azacitidine vs. azacitidine + enasidenib was reported by Dinardo et al.¹ The primary endpoint was overall response rate. The study included 101 adult patients with newly diagnosed mutant-IDH2 acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy. They were randomly assigned to enasidenib and azacitidine (Ena-AZA, n = 68) or azacitidine alone (AZA, n = 33). The overall response rate was significantly higher in patients receiving Ena-AZA vs. AZA (74% vs. 36%; odds ratio 4.9; P = .0003). More importantly, the rates of complete remission/complete remission with partial hematologic recovery was higher with Ena-AZA vs. AZA (57% vs. 18% P = .0001). The duration of response was 24.1 months vs 9.9 months for the Ena-AZA vs AZA group. Despite the higher and more durable responses with Ena+AZA, there was no difference in overall survival. The authors attributed that to patients receiving other effective therapies after disease progression. Overall patients tolerated the combination therapy well. The most frequent grade 3 or 4 events in the Ena-AZA vs. AZA groups were thrombocytopenia (37% vs. 19%) and neutropenia (37% vs. 25%).  

Another study from the NCRI AML 16 trial demonstrated that reduced intensity conditioning (RIC) transplant in first remission vs. chemotherapy alone improved survival in older patients with AML who lacked favorable risk cytogenetics and were considered fit for intensive treatment. During a median follow-up of 60 months from remission, patients receiving RIC transplant vs. no transplant had superior survival (37% vs. 20%; hazard ratio [HR] 0.67; P < .001). Survival benefit with transplant in first remission vs. chemotherapy alone was observed across all Wheatley risk groups (adjusted HR 0.68; P < .001). The trial including 932 patients (age 60-70 years) with AML who entered remission and lacked favorable risk. Of these, 144 underwent RIC transplants from either matched sibling donors (n = 52) or matched unrelated donors (n = 92).

The outcome of patients with AML and central nervous system (CNS) involvement at presentation was reported by Ganzel et al. In that study, the investigators evaluated the incidence of CNS involvement in 11 consecutive Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) clinical trials. The incidence of CNS incolvement was 1.111 % (36 of 3240 patients). CNS involvement had no effect on remission rates or survival.

References

1. Dinardo CD et al. Enasidenib plus azacitidine versus azacitidine alone in patients with newly diagnosed, mutant-IDH2 acute myeloid leukaemia (AG221-AML-005): a single-arm, phase 1b and randomised, phase 2 trial. Lancet Oncol. 2021;22(11):P1597-1608 (Nov 1).
2. Russell NH et al. Outcomes of older patients aged 60 to 70 years undergoing reduced intensity transplant for acute myeloblastic leukemia: results of the NCRI acute myeloid leukemia 16 trial. Haematologica. 2021(Oct 14).
3. Ganzel C et al. CNS involvement in AML at diagnosis is rare and does not affect response or survival: data from 11 ECOG-ACRIN trials. Blood Adv. 2021(Nov 12);5(22):4560-4568. doi: 10.1182/bloodadvances.2021004999.

This month, the phase II randomized study of azacitidine vs. azacitidine + enasidenib was reported by Dinardo et al.¹ The primary endpoint was overall response rate. The study included 101 adult patients with newly diagnosed mutant-IDH2 acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy. They were randomly assigned to enasidenib and azacitidine (Ena-AZA, n = 68) or azacitidine alone (AZA, n = 33). The overall response rate was significantly higher in patients receiving Ena-AZA vs. AZA (74% vs. 36%; odds ratio 4.9; P = .0003). More importantly, the rates of complete remission/complete remission with partial hematologic recovery was higher with Ena-AZA vs. AZA (57% vs. 18% P = .0001). The duration of response was 24.1 months vs 9.9 months for the Ena-AZA vs AZA group. Despite the higher and more durable responses with Ena+AZA, there was no difference in overall survival. The authors attributed that to patients receiving other effective therapies after disease progression. Overall patients tolerated the combination therapy well. The most frequent grade 3 or 4 events in the Ena-AZA vs. AZA groups were thrombocytopenia (37% vs. 19%) and neutropenia (37% vs. 25%).  

Another study from the NCRI AML 16 trial demonstrated that reduced intensity conditioning (RIC) transplant in first remission vs. chemotherapy alone improved survival in older patients with AML who lacked favorable risk cytogenetics and were considered fit for intensive treatment. During a median follow-up of 60 months from remission, patients receiving RIC transplant vs. no transplant had superior survival (37% vs. 20%; hazard ratio [HR] 0.67; P < .001). Survival benefit with transplant in first remission vs. chemotherapy alone was observed across all Wheatley risk groups (adjusted HR 0.68; P < .001). The trial including 932 patients (age 60-70 years) with AML who entered remission and lacked favorable risk. Of these, 144 underwent RIC transplants from either matched sibling donors (n = 52) or matched unrelated donors (n = 92).

The outcome of patients with AML and central nervous system (CNS) involvement at presentation was reported by Ganzel et al. In that study, the investigators evaluated the incidence of CNS involvement in 11 consecutive Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) clinical trials. The incidence of CNS incolvement was 1.111 % (36 of 3240 patients). CNS involvement had no effect on remission rates or survival.

References

1. Dinardo CD et al. Enasidenib plus azacitidine versus azacitidine alone in patients with newly diagnosed, mutant-IDH2 acute myeloid leukaemia (AG221-AML-005): a single-arm, phase 1b and randomised, phase 2 trial. Lancet Oncol. 2021;22(11):P1597-1608 (Nov 1).
2. Russell NH et al. Outcomes of older patients aged 60 to 70 years undergoing reduced intensity transplant for acute myeloblastic leukemia: results of the NCRI acute myeloid leukemia 16 trial. Haematologica. 2021(Oct 14).
3. Ganzel C et al. CNS involvement in AML at diagnosis is rare and does not affect response or survival: data from 11 ECOG-ACRIN trials. Blood Adv. 2021(Nov 12);5(22):4560-4568. doi: 10.1182/bloodadvances.2021004999.

This month, the phase II randomized study of azacitidine vs. azacitidine + enasidenib was reported by Dinardo et al.¹ The primary endpoint was overall response rate. The study included 101 adult patients with newly diagnosed mutant-IDH2 acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy. They were randomly assigned to enasidenib and azacitidine (Ena-AZA, n = 68) or azacitidine alone (AZA, n = 33). The overall response rate was significantly higher in patients receiving Ena-AZA vs. AZA (74% vs. 36%; odds ratio 4.9; P = .0003). More importantly, the rates of complete remission/complete remission with partial hematologic recovery was higher with Ena-AZA vs. AZA (57% vs. 18% P = .0001). The duration of response was 24.1 months vs 9.9 months for the Ena-AZA vs AZA group. Despite the higher and more durable responses with Ena+AZA, there was no difference in overall survival. The authors attributed that to patients receiving other effective therapies after disease progression. Overall patients tolerated the combination therapy well. The most frequent grade 3 or 4 events in the Ena-AZA vs. AZA groups were thrombocytopenia (37% vs. 19%) and neutropenia (37% vs. 25%).  

Another study from the NCRI AML 16 trial demonstrated that reduced intensity conditioning (RIC) transplant in first remission vs. chemotherapy alone improved survival in older patients with AML who lacked favorable risk cytogenetics and were considered fit for intensive treatment. During a median follow-up of 60 months from remission, patients receiving RIC transplant vs. no transplant had superior survival (37% vs. 20%; hazard ratio [HR] 0.67; P < .001). Survival benefit with transplant in first remission vs. chemotherapy alone was observed across all Wheatley risk groups (adjusted HR 0.68; P < .001). The trial including 932 patients (age 60-70 years) with AML who entered remission and lacked favorable risk. Of these, 144 underwent RIC transplants from either matched sibling donors (n = 52) or matched unrelated donors (n = 92).

The outcome of patients with AML and central nervous system (CNS) involvement at presentation was reported by Ganzel et al. In that study, the investigators evaluated the incidence of CNS involvement in 11 consecutive Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) clinical trials. The incidence of CNS incolvement was 1.111 % (36 of 3240 patients). CNS involvement had no effect on remission rates or survival.

References

1. Dinardo CD et al. Enasidenib plus azacitidine versus azacitidine alone in patients with newly diagnosed, mutant-IDH2 acute myeloid leukaemia (AG221-AML-005): a single-arm, phase 1b and randomised, phase 2 trial. Lancet Oncol. 2021;22(11):P1597-1608 (Nov 1).
2. Russell NH et al. Outcomes of older patients aged 60 to 70 years undergoing reduced intensity transplant for acute myeloblastic leukemia: results of the NCRI acute myeloid leukemia 16 trial. Haematologica. 2021(Oct 14).
3. Ganzel C et al. CNS involvement in AML at diagnosis is rare and does not affect response or survival: data from 11 ECOG-ACRIN trials. Blood Adv. 2021(Nov 12);5(22):4560-4568. doi: 10.1182/bloodadvances.2021004999.

Patients who adhere to their tyrosine kinase inhibitor (TKI) medication regimen will achieve CML survival goals that would be expected for their age group. Imatinib is a first generation TKI inhibitor.  In a recent post hoc analysis of the ADAGIO study patients, Obeng-Kusi M et al¹ showed that compared with 90% adherence, a 100% adherence to imatinib was associated with a 2-fold increase in achieving or maintaining treatment response in patients with chronic myeloid leukemia (CML), highlighting the urgent need to assess and promote patient adherence. There is virtually no margin for nonadherence, if the objective is to optimize the likelihood of treatment response, and a minimal margin to avoid impaired treatment response.

On the same topic, Davis TC et al.²also recently reported a study of suboptimal adherence to TKI. From the 86 patients with CML studied, almost 17.9% of participants reported nonadherence, i.e., missing at least 1 dose of CML medication in the previous week. The main reason that patients reported nonadherence were side effects, a busy schedule, and the difficulty of complying daily with the TKI regimen.

Cardiovascular adverse events (AE) have been described with TKI treatment at different rates, but cardiovascular risk stratification was not included in the design of many trials. Baggio D et al³  in a retrospective study included 88 patients with CML treated with any TKI and a median follow up of 3.8 months. They described the rates of major cardiovascular AEs by combining age, history of prior cardiovascular diseases, and Framingham risk score, along with additional insights from coronary artery calcium scoring (CACS). The authors found cardiovascular AEs in 0%, 10%, and 19%, of the low-, intermediate-, and high-risk groups respectively. By using CACS score they were able to reclassify patients from intermediate to low risk and none of those patients experienced a major adverse cardiovascular event.

The use of kinase domain mutation analysis at diagnosis is not a recommended practice by the National Comprehensive Cancer Network (NCCN) or the European Leukemia Net (ELN), but is reserved for use in patents who failed first or subsequent lines of therapies. Furthermore, previous publications in the topic have showed discordant results. More recently, the use of ultra-deep sequencing has detected low-frequency genetic mutations with high sensitivity. Park H et al.⁴ recently described the most common mutations found in a population of 50 CML patients treated with nilotinib. V299 L mutation associated with dasatinib resistance and nilotinib sensitivity were observed in 98% of patients. Two uncommon mutations S417Y and the V371A were associated with reduced molecular response.

References

1. Obeng-Kusi M et al. No margin for non-adherence: Probabilistic Kaplan-Meier modeling of imatinib non-adherence and treatment response in CML (ADAGIO study). Leuk Res. 2021;111:106734 (Oct 21).
2. Davis TC et al. Assessment of oral chemotherapy nonadherence in chronic myeloid leukemia patients using brief measures in community cancer clinics: a pilot study. Int J Environ Res Public Health. 2021;18(21):11045 (Oct 21).
3. Baggio D et al. Prediction of cardiovascular events in patients with chronic myeloid leukaemia using baseline risk factors and coronary artery calcium scoring. Intern Med J. 2021;51(10):1736-40 (Oct 18).  
4. Park H et al. Ultra-deep sequencing mutation analysis of the BCR/ABL1 kinase domain in newly diagnosed chronic myeloid leukemia patients. Leuk Res. 2021;111:106728 (Oct 15).

Patients who adhere to their tyrosine kinase inhibitor (TKI) medication regimen will achieve CML survival goals that would be expected for their age group. Imatinib is a first generation TKI inhibitor.  In a recent post hoc analysis of the ADAGIO study patients, Obeng-Kusi M et al¹ showed that compared with 90% adherence, a 100% adherence to imatinib was associated with a 2-fold increase in achieving or maintaining treatment response in patients with chronic myeloid leukemia (CML), highlighting the urgent need to assess and promote patient adherence. There is virtually no margin for nonadherence, if the objective is to optimize the likelihood of treatment response, and a minimal margin to avoid impaired treatment response.

On the same topic, Davis TC et al.²also recently reported a study of suboptimal adherence to TKI. From the 86 patients with CML studied, almost 17.9% of participants reported nonadherence, i.e., missing at least 1 dose of CML medication in the previous week. The main reason that patients reported nonadherence were side effects, a busy schedule, and the difficulty of complying daily with the TKI regimen.

Cardiovascular adverse events (AE) have been described with TKI treatment at different rates, but cardiovascular risk stratification was not included in the design of many trials. Baggio D et al³  in a retrospective study included 88 patients with CML treated with any TKI and a median follow up of 3.8 months. They described the rates of major cardiovascular AEs by combining age, history of prior cardiovascular diseases, and Framingham risk score, along with additional insights from coronary artery calcium scoring (CACS). The authors found cardiovascular AEs in 0%, 10%, and 19%, of the low-, intermediate-, and high-risk groups respectively. By using CACS score they were able to reclassify patients from intermediate to low risk and none of those patients experienced a major adverse cardiovascular event.

The use of kinase domain mutation analysis at diagnosis is not a recommended practice by the National Comprehensive Cancer Network (NCCN) or the European Leukemia Net (ELN), but is reserved for use in patents who failed first or subsequent lines of therapies. Furthermore, previous publications in the topic have showed discordant results. More recently, the use of ultra-deep sequencing has detected low-frequency genetic mutations with high sensitivity. Park H et al.⁴ recently described the most common mutations found in a population of 50 CML patients treated with nilotinib. V299 L mutation associated with dasatinib resistance and nilotinib sensitivity were observed in 98% of patients. Two uncommon mutations S417Y and the V371A were associated with reduced molecular response.

References

1. Obeng-Kusi M et al. No margin for non-adherence: Probabilistic Kaplan-Meier modeling of imatinib non-adherence and treatment response in CML (ADAGIO study). Leuk Res. 2021;111:106734 (Oct 21).
2. Davis TC et al. Assessment of oral chemotherapy nonadherence in chronic myeloid leukemia patients using brief measures in community cancer clinics: a pilot study. Int J Environ Res Public Health. 2021;18(21):11045 (Oct 21).
3. Baggio D et al. Prediction of cardiovascular events in patients with chronic myeloid leukaemia using baseline risk factors and coronary artery calcium scoring. Intern Med J. 2021;51(10):1736-40 (Oct 18).  
4. Park H et al. Ultra-deep sequencing mutation analysis of the BCR/ABL1 kinase domain in newly diagnosed chronic myeloid leukemia patients. Leuk Res. 2021;111:106728 (Oct 15).

Patients who adhere to their tyrosine kinase inhibitor (TKI) medication regimen will achieve CML survival goals that would be expected for their age group. Imatinib is a first generation TKI inhibitor.  In a recent post hoc analysis of the ADAGIO study patients, Obeng-Kusi M et al¹ showed that compared with 90% adherence, a 100% adherence to imatinib was associated with a 2-fold increase in achieving or maintaining treatment response in patients with chronic myeloid leukemia (CML), highlighting the urgent need to assess and promote patient adherence. There is virtually no margin for nonadherence, if the objective is to optimize the likelihood of treatment response, and a minimal margin to avoid impaired treatment response.

On the same topic, Davis TC et al.²also recently reported a study of suboptimal adherence to TKI. From the 86 patients with CML studied, almost 17.9% of participants reported nonadherence, i.e., missing at least 1 dose of CML medication in the previous week. The main reason that patients reported nonadherence were side effects, a busy schedule, and the difficulty of complying daily with the TKI regimen.

Cardiovascular adverse events (AE) have been described with TKI treatment at different rates, but cardiovascular risk stratification was not included in the design of many trials. Baggio D et al³  in a retrospective study included 88 patients with CML treated with any TKI and a median follow up of 3.8 months. They described the rates of major cardiovascular AEs by combining age, history of prior cardiovascular diseases, and Framingham risk score, along with additional insights from coronary artery calcium scoring (CACS). The authors found cardiovascular AEs in 0%, 10%, and 19%, of the low-, intermediate-, and high-risk groups respectively. By using CACS score they were able to reclassify patients from intermediate to low risk and none of those patients experienced a major adverse cardiovascular event.

The use of kinase domain mutation analysis at diagnosis is not a recommended practice by the National Comprehensive Cancer Network (NCCN) or the European Leukemia Net (ELN), but is reserved for use in patents who failed first or subsequent lines of therapies. Furthermore, previous publications in the topic have showed discordant results. More recently, the use of ultra-deep sequencing has detected low-frequency genetic mutations with high sensitivity. Park H et al.⁴ recently described the most common mutations found in a population of 50 CML patients treated with nilotinib. V299 L mutation associated with dasatinib resistance and nilotinib sensitivity were observed in 98% of patients. Two uncommon mutations S417Y and the V371A were associated with reduced molecular response.

References

1. Obeng-Kusi M et al. No margin for non-adherence: Probabilistic Kaplan-Meier modeling of imatinib non-adherence and treatment response in CML (ADAGIO study). Leuk Res. 2021;111:106734 (Oct 21).
2. Davis TC et al. Assessment of oral chemotherapy nonadherence in chronic myeloid leukemia patients using brief measures in community cancer clinics: a pilot study. Int J Environ Res Public Health. 2021;18(21):11045 (Oct 21).
3. Baggio D et al. Prediction of cardiovascular events in patients with chronic myeloid leukaemia using baseline risk factors and coronary artery calcium scoring. Intern Med J. 2021;51(10):1736-40 (Oct 18).  
4. Park H et al. Ultra-deep sequencing mutation analysis of the BCR/ABL1 kinase domain in newly diagnosed chronic myeloid leukemia patients. Leuk Res. 2021;111:106728 (Oct 15).

Many people with rheumatoid arthritis (RA) have concomitant hand osteoarthritis (OA). This Swiss cohort study by Lechtenboehmer et al¹ using a longitudinal registry of RA patients examined characteristics of RA patients who had progression of radiographic hand OA. Of over 1,300 patients who had radiographic distal interphalangeal (DIP) OA at baseline, a substantial fraction had progression of OA with osteophyte formation, joint space narrowing, and subchondral sclerosis. In subgroup analysis, biologic disease-modifying antirheumatic drug (bDMARD) use was associated with osteophyte formation, while of nearly 900 patients without radiographic OA at baseline, bDMARD use was not associated with development of DIP OA. While the authors postulate that this may be due to osteoanabolic effects of bDMARDs, in this real-world analysis the association does not imply a causative role for bDMARDs as additional confounders may exist and the onset/timing of progression is unknown. Still, the association deserves attention in controlled and long-term studies.

Another condition known to affect older adults is sarcopenia; in addition to aging, poor nutrition, lack of exercise, and autoimmune disease are thought to contribute to sarcopenia. RA is associated with an increased risk of sarcopenia. A cross-sectional study of cohort of Japanese women by Minamino et al.² of RA examines the potential relationship between 25-OH vitamin D levels and sarcopenia. Participants were over the age of 60 and not taking vitamin D supplements. Low vitamin D levels, as well as age, 28-Joint RA Disease Activity Score (DAS-28), and health assessment questionnaire disability index (HAQ), were associated with the prevalence of severe sarcopenia, including the separate components of muscle mass, physical performance, and strength. Although this does not prove causation, the known decrease in vitamin D receptors in muscle nuclei with aging lends pathophysiologic support to vitamin D’s role in sarcopenia. Whether this plays a larger role in RA-related sarcopenia also remains to be seen.

Several recent studies have expanded our awareness of respiratory illness and exposure outside of cigarette smoking as potentially associated with RA risk. This single-center case control study by Kronzer et al³ looked at respiratory disease diagnosis (based on ICD10 code) at least two years prior to RA diagnosis. Acute and chronic sinusitis, as well as pharyngitis, were associated with increased risk of RA, even adjusting for the known risk of smoking, raising the possibility of a role for the upper respiratory mucosa in RA pathogenesis. Whether this association is a sign of immune dysregulation instead or a result of other respiratory exposures is a question that should be further investigated given this growing body of evidence of respiratory involvement in RA pathogenesis.

In terms of other factors that influence the development of autoimmune disease, there is evidence of the involvement of the gut microbiome in RA pathogenesis, as well as public interest in the possibility of an optimal diet, such as the “Mediterranean diet” for control of arthritis symptoms. The recent Swedish crossover Anti-inflammatory Diet In Rheumatoid Arthritis (ADIRA) study by Turesson Wadell et al⁴ examined effects of a “typical” and “anti-inflammatory” diet with whole grains, fruits, nuts, legumes, fatty fish, and probiotics in patients with RA. Prior work suggested that the anti-inflammatory diet was associated with lower RA disease activity and inflammatory markers. Only 44 patients completed the 10 week study, perhaps contributing to the lack of differences seen in functional measures, pain, fatigue, and morning stiffness at the end of the intervention. Changes in medications may have masked dietary effects in this small study and a longer study period may be necessary to assess effects. Given the lack of evidence in this area, further research is of course needed, but this study represents an initial attempt at rigorous examination and could be suggested to interested and motivated patients as generally safe.

References

1. Lechtenboehmer CA et al. Increased radiographic progression of distal hand osteoarthritis occurring during biologic DMARD monotherapy for concomitant rheumatoid arthritis. Arthritis Res Ther. 2021;23:267 (Oct 26).
2. Minamino H et al. Serum vitamin D status inversely associates with a prevalence of severe sarcopenia among female patients with rheumatoid arthritis. Sci Rep. 2021;11:20485 (Oct 14).
3. Kronzer VL et al. Association of sinusitis and upper respiratory tract diseases with incident rheumatoid arthritis: A case-control study. J Rheumatol 2021(Oct 15).
4. Turesson Wadell A et al. Effects on health-related quality of life in the randomized, controlled crossover trial ADIRA (Anti-inflammatory Diet In Rheumatoid Arthritis). PLoS One. 2021(Oct 14).

Many people with rheumatoid arthritis (RA) have concomitant hand osteoarthritis (OA). This Swiss cohort study by Lechtenboehmer et al¹ using a longitudinal registry of RA patients examined characteristics of RA patients who had progression of radiographic hand OA. Of over 1,300 patients who had radiographic distal interphalangeal (DIP) OA at baseline, a substantial fraction had progression of OA with osteophyte formation, joint space narrowing, and subchondral sclerosis. In subgroup analysis, biologic disease-modifying antirheumatic drug (bDMARD) use was associated with osteophyte formation, while of nearly 900 patients without radiographic OA at baseline, bDMARD use was not associated with development of DIP OA. While the authors postulate that this may be due to osteoanabolic effects of bDMARDs, in this real-world analysis the association does not imply a causative role for bDMARDs as additional confounders may exist and the onset/timing of progression is unknown. Still, the association deserves attention in controlled and long-term studies.

Another condition known to affect older adults is sarcopenia; in addition to aging, poor nutrition, lack of exercise, and autoimmune disease are thought to contribute to sarcopenia. RA is associated with an increased risk of sarcopenia. A cross-sectional study of cohort of Japanese women by Minamino et al.² of RA examines the potential relationship between 25-OH vitamin D levels and sarcopenia. Participants were over the age of 60 and not taking vitamin D supplements. Low vitamin D levels, as well as age, 28-Joint RA Disease Activity Score (DAS-28), and health assessment questionnaire disability index (HAQ), were associated with the prevalence of severe sarcopenia, including the separate components of muscle mass, physical performance, and strength. Although this does not prove causation, the known decrease in vitamin D receptors in muscle nuclei with aging lends pathophysiologic support to vitamin D’s role in sarcopenia. Whether this plays a larger role in RA-related sarcopenia also remains to be seen.

Several recent studies have expanded our awareness of respiratory illness and exposure outside of cigarette smoking as potentially associated with RA risk. This single-center case control study by Kronzer et al³ looked at respiratory disease diagnosis (based on ICD10 code) at least two years prior to RA diagnosis. Acute and chronic sinusitis, as well as pharyngitis, were associated with increased risk of RA, even adjusting for the known risk of smoking, raising the possibility of a role for the upper respiratory mucosa in RA pathogenesis. Whether this association is a sign of immune dysregulation instead or a result of other respiratory exposures is a question that should be further investigated given this growing body of evidence of respiratory involvement in RA pathogenesis.

In terms of other factors that influence the development of autoimmune disease, there is evidence of the involvement of the gut microbiome in RA pathogenesis, as well as public interest in the possibility of an optimal diet, such as the “Mediterranean diet” for control of arthritis symptoms. The recent Swedish crossover Anti-inflammatory Diet In Rheumatoid Arthritis (ADIRA) study by Turesson Wadell et al⁴ examined effects of a “typical” and “anti-inflammatory” diet with whole grains, fruits, nuts, legumes, fatty fish, and probiotics in patients with RA. Prior work suggested that the anti-inflammatory diet was associated with lower RA disease activity and inflammatory markers. Only 44 patients completed the 10 week study, perhaps contributing to the lack of differences seen in functional measures, pain, fatigue, and morning stiffness at the end of the intervention. Changes in medications may have masked dietary effects in this small study and a longer study period may be necessary to assess effects. Given the lack of evidence in this area, further research is of course needed, but this study represents an initial attempt at rigorous examination and could be suggested to interested and motivated patients as generally safe.

References

1. Lechtenboehmer CA et al. Increased radiographic progression of distal hand osteoarthritis occurring during biologic DMARD monotherapy for concomitant rheumatoid arthritis. Arthritis Res Ther. 2021;23:267 (Oct 26).
2. Minamino H et al. Serum vitamin D status inversely associates with a prevalence of severe sarcopenia among female patients with rheumatoid arthritis. Sci Rep. 2021;11:20485 (Oct 14).
3. Kronzer VL et al. Association of sinusitis and upper respiratory tract diseases with incident rheumatoid arthritis: A case-control study. J Rheumatol 2021(Oct 15).
4. Turesson Wadell A et al. Effects on health-related quality of life in the randomized, controlled crossover trial ADIRA (Anti-inflammatory Diet In Rheumatoid Arthritis). PLoS One. 2021(Oct 14).

Many people with rheumatoid arthritis (RA) have concomitant hand osteoarthritis (OA). This Swiss cohort study by Lechtenboehmer et al¹ using a longitudinal registry of RA patients examined characteristics of RA patients who had progression of radiographic hand OA. Of over 1,300 patients who had radiographic distal interphalangeal (DIP) OA at baseline, a substantial fraction had progression of OA with osteophyte formation, joint space narrowing, and subchondral sclerosis. In subgroup analysis, biologic disease-modifying antirheumatic drug (bDMARD) use was associated with osteophyte formation, while of nearly 900 patients without radiographic OA at baseline, bDMARD use was not associated with development of DIP OA. While the authors postulate that this may be due to osteoanabolic effects of bDMARDs, in this real-world analysis the association does not imply a causative role for bDMARDs as additional confounders may exist and the onset/timing of progression is unknown. Still, the association deserves attention in controlled and long-term studies.

Another condition known to affect older adults is sarcopenia; in addition to aging, poor nutrition, lack of exercise, and autoimmune disease are thought to contribute to sarcopenia. RA is associated with an increased risk of sarcopenia. A cross-sectional study of cohort of Japanese women by Minamino et al.² of RA examines the potential relationship between 25-OH vitamin D levels and sarcopenia. Participants were over the age of 60 and not taking vitamin D supplements. Low vitamin D levels, as well as age, 28-Joint RA Disease Activity Score (DAS-28), and health assessment questionnaire disability index (HAQ), were associated with the prevalence of severe sarcopenia, including the separate components of muscle mass, physical performance, and strength. Although this does not prove causation, the known decrease in vitamin D receptors in muscle nuclei with aging lends pathophysiologic support to vitamin D’s role in sarcopenia. Whether this plays a larger role in RA-related sarcopenia also remains to be seen.

Several recent studies have expanded our awareness of respiratory illness and exposure outside of cigarette smoking as potentially associated with RA risk. This single-center case control study by Kronzer et al³ looked at respiratory disease diagnosis (based on ICD10 code) at least two years prior to RA diagnosis. Acute and chronic sinusitis, as well as pharyngitis, were associated with increased risk of RA, even adjusting for the known risk of smoking, raising the possibility of a role for the upper respiratory mucosa in RA pathogenesis. Whether this association is a sign of immune dysregulation instead or a result of other respiratory exposures is a question that should be further investigated given this growing body of evidence of respiratory involvement in RA pathogenesis.

In terms of other factors that influence the development of autoimmune disease, there is evidence of the involvement of the gut microbiome in RA pathogenesis, as well as public interest in the possibility of an optimal diet, such as the “Mediterranean diet” for control of arthritis symptoms. The recent Swedish crossover Anti-inflammatory Diet In Rheumatoid Arthritis (ADIRA) study by Turesson Wadell et al⁴ examined effects of a “typical” and “anti-inflammatory” diet with whole grains, fruits, nuts, legumes, fatty fish, and probiotics in patients with RA. Prior work suggested that the anti-inflammatory diet was associated with lower RA disease activity and inflammatory markers. Only 44 patients completed the 10 week study, perhaps contributing to the lack of differences seen in functional measures, pain, fatigue, and morning stiffness at the end of the intervention. Changes in medications may have masked dietary effects in this small study and a longer study period may be necessary to assess effects. Given the lack of evidence in this area, further research is of course needed, but this study represents an initial attempt at rigorous examination and could be suggested to interested and motivated patients as generally safe.

References

1. Lechtenboehmer CA et al. Increased radiographic progression of distal hand osteoarthritis occurring during biologic DMARD monotherapy for concomitant rheumatoid arthritis. Arthritis Res Ther. 2021;23:267 (Oct 26).
2. Minamino H et al. Serum vitamin D status inversely associates with a prevalence of severe sarcopenia among female patients with rheumatoid arthritis. Sci Rep. 2021;11:20485 (Oct 14).
3. Kronzer VL et al. Association of sinusitis and upper respiratory tract diseases with incident rheumatoid arthritis: A case-control study. J Rheumatol 2021(Oct 15).
4. Turesson Wadell A et al. Effects on health-related quality of life in the randomized, controlled crossover trial ADIRA (Anti-inflammatory Diet In Rheumatoid Arthritis). PLoS One. 2021(Oct 14).

Research published in November has provided us with insights on the impact of psoriatic arthritis (PsA) as well as treatment outcomes. Although PsA often affects women of child-bearing age, data on pregnancy outcomes in PsA is scarce. To evaluate pregnancy outcomes in patients with severe PsA, Remaeus et al¹ conducted a Swedish nationwide register-based cohort study of births from Jul 1 2007 to Dec 31 2017. A total of 921 PsA- pregnancies and 9210 non-PsA-pregnancies (matched on maternal age, year, and parity) were identified. Pregnancy in PsA vs. non-PsA women were associated with increased risk for preterm birth (adjusted odds ratio [aOR] 1.69; 95% CI 1.27-2.24), elective cesarean delivery (CD; aOR 1.77; 95% CI 1.43-2.20), and emergency CD (aOR 1.42; 95% CI 1.10-1.84) with the risk even more pronounced in pregnancies in women with PsA with exposure to antirheumatic treatment any time before or during pregnancy (surrogate for disease severity- preterm birth: aOR 1.98; 95% CI 1.27-2.86; elective CD: aOR 1.96; 95% CI 1.47-2.63; and emergency CD: aOR 1.67; 95% CI 1.18-2.36). Thus, pregnant women with PsA, particularly those requiring antirheumatic treatment, are at increased risk for adverse pregnancy outcomes and therefore should be counselled appropriately.

Depression is a well-known comorbidity of PsA. However, little is known about the impact of the COVID-19 pandemic on the prevalence of depressive symptoms in PsA patients. Engelbrecht et al² evaluated 89 patients with PsA participating in the German multicenter RheumaDatenRhePort registry. Symptoms of depression were assessed using the Patient Health Questionnaire-2 (PHQ-2). The majority of patients scored <2 on the PHQ-2 indicating that they did not have depressive symptoms during (85.39%) and prior to (83.15%) the pandemic. The prevalence of depressive symptoms was not significantly different before and during the pandemic, irrespective of disease activity. Thus, contrary to expectations, the COVID-19 pandemic did not increase the occurrence of depressive symptoms among patients with PsA.

With regard to longer-term treatment efficacy and safety of recently approved advanced therapies for PsA, McInnes et al reported 2-year results from the from the Phase-3 DISCOVER-2 trial that included 739 biologic-naive patients with active PsA. At week 100, ACR20 response was achieved by 76%, 74%, and 68% of patients who initially were randomized to receive guselkumab every 4 weeks, every 8 weeks, or placebo, respectively, indicating a durable response. No new safety signals were identified. The 56-week efficacy and safety results from SELECT-PsA 1 trial with upadacitinib reported by McInnes et al^4,5 showed that of 1705 patients randomized, 1419 (83.2%) completed 56 weeks of treatment. A higher proportion of patients achieved ACR20 response with upadacitinib (15 mg, 74.4%; 30 mg, 74.7%) vs. adalimumab (68.5%; P = .046) at week 56. No new safety signals were identified.

Safety, especially risk of infection, remains a significant concern when treating patients with biologics, especially tumor necrosis factor inhibitors (TNFi). Patients with rheumatoid arthritis (RA) are known to have a higher risk of infection, but data are scarce regarding the risk of serious infections in patients with PsA treated with TNFi and the comparative risk of infection in TNFi-treated RA patients versus patients with PsA. Using data from 1,352 and 1,007 patients with RA and PsA, respectively, followed in the prospective multi-center NORwegian-Disease Modifying Anti-Rheumatic Drug (NOR-DMARD) registry, Christensen et al report that patients with PsA vs. RA had a lower risk of contracting serious infections (adjusted hazard ratio 0.65; P = .025).

References

1. Remaeus K et al. Pregnancy outcomes in women with psoriatic arthritis with respect to presence and timing of antirheumatic treatment. Arthritis Rheumatol. 2021(Oct 20).
2. Englbrecht M et al. Prevalence of depressive symptoms in patients with psoriatic arthritis: have numbers changed during the COVID-19 pandemic? Front Med (Lausanne). 2021(Nov 1);8:74826
3. McInnes IB et al. Long-term efficacy and safety of guselkumab, a monoclonal antibody specific to the p19 subunit of interleukin-23, through 2 years: results from a phase 3, randomized, double-blind, placebo-controlled study conducted in biologic-naïve patients with active psoriatic arthritis. Arthritis Rheumatol. 2021(Nov 1).
4. McInnes IB et al. Upadacitinib in patients with psoriatic arthritis and an inadequate response to non-biological therapy: 56-week data from the phase 3 SELECT-PsA 1 study.  RMD Open. 2021;7:e001838 (Oct 18).
5. Christensen IE et al. Serious infections in patients with rheumatoid arthritis and psoriatic arthritis treated with tumour necrosis factor inhibitors: data from register linkage of the NOR-DMARD study. Ann Rheum Dis. 2021(Oct 8). Correction: Upadacitinib in patients with psoriatic arthritis and an inadequate response to non-biological therapy: 56-week data from the phase 3 SELECT-PsA 1 study. RMD Open. 2021 Nov;7(3):e001838corr1.

Research published in November has provided us with insights on the impact of psoriatic arthritis (PsA) as well as treatment outcomes. Although PsA often affects women of child-bearing age, data on pregnancy outcomes in PsA is scarce. To evaluate pregnancy outcomes in patients with severe PsA, Remaeus et al¹ conducted a Swedish nationwide register-based cohort study of births from Jul 1 2007 to Dec 31 2017. A total of 921 PsA- pregnancies and 9210 non-PsA-pregnancies (matched on maternal age, year, and parity) were identified. Pregnancy in PsA vs. non-PsA women were associated with increased risk for preterm birth (adjusted odds ratio [aOR] 1.69; 95% CI 1.27-2.24), elective cesarean delivery (CD; aOR 1.77; 95% CI 1.43-2.20), and emergency CD (aOR 1.42; 95% CI 1.10-1.84) with the risk even more pronounced in pregnancies in women with PsA with exposure to antirheumatic treatment any time before or during pregnancy (surrogate for disease severity- preterm birth: aOR 1.98; 95% CI 1.27-2.86; elective CD: aOR 1.96; 95% CI 1.47-2.63; and emergency CD: aOR 1.67; 95% CI 1.18-2.36). Thus, pregnant women with PsA, particularly those requiring antirheumatic treatment, are at increased risk for adverse pregnancy outcomes and therefore should be counselled appropriately.

Depression is a well-known comorbidity of PsA. However, little is known about the impact of the COVID-19 pandemic on the prevalence of depressive symptoms in PsA patients. Engelbrecht et al² evaluated 89 patients with PsA participating in the German multicenter RheumaDatenRhePort registry. Symptoms of depression were assessed using the Patient Health Questionnaire-2 (PHQ-2). The majority of patients scored <2 on the PHQ-2 indicating that they did not have depressive symptoms during (85.39%) and prior to (83.15%) the pandemic. The prevalence of depressive symptoms was not significantly different before and during the pandemic, irrespective of disease activity. Thus, contrary to expectations, the COVID-19 pandemic did not increase the occurrence of depressive symptoms among patients with PsA.

With regard to longer-term treatment efficacy and safety of recently approved advanced therapies for PsA, McInnes et al reported 2-year results from the from the Phase-3 DISCOVER-2 trial that included 739 biologic-naive patients with active PsA. At week 100, ACR20 response was achieved by 76%, 74%, and 68% of patients who initially were randomized to receive guselkumab every 4 weeks, every 8 weeks, or placebo, respectively, indicating a durable response. No new safety signals were identified. The 56-week efficacy and safety results from SELECT-PsA 1 trial with upadacitinib reported by McInnes et al^4,5 showed that of 1705 patients randomized, 1419 (83.2%) completed 56 weeks of treatment. A higher proportion of patients achieved ACR20 response with upadacitinib (15 mg, 74.4%; 30 mg, 74.7%) vs. adalimumab (68.5%; P = .046) at week 56. No new safety signals were identified.

Safety, especially risk of infection, remains a significant concern when treating patients with biologics, especially tumor necrosis factor inhibitors (TNFi). Patients with rheumatoid arthritis (RA) are known to have a higher risk of infection, but data are scarce regarding the risk of serious infections in patients with PsA treated with TNFi and the comparative risk of infection in TNFi-treated RA patients versus patients with PsA. Using data from 1,352 and 1,007 patients with RA and PsA, respectively, followed in the prospective multi-center NORwegian-Disease Modifying Anti-Rheumatic Drug (NOR-DMARD) registry, Christensen et al report that patients with PsA vs. RA had a lower risk of contracting serious infections (adjusted hazard ratio 0.65; P = .025).

References

1. Remaeus K et al. Pregnancy outcomes in women with psoriatic arthritis with respect to presence and timing of antirheumatic treatment. Arthritis Rheumatol. 2021(Oct 20).
2. Englbrecht M et al. Prevalence of depressive symptoms in patients with psoriatic arthritis: have numbers changed during the COVID-19 pandemic? Front Med (Lausanne). 2021(Nov 1);8:74826
3. McInnes IB et al. Long-term efficacy and safety of guselkumab, a monoclonal antibody specific to the p19 subunit of interleukin-23, through 2 years: results from a phase 3, randomized, double-blind, placebo-controlled study conducted in biologic-naïve patients with active psoriatic arthritis. Arthritis Rheumatol. 2021(Nov 1).
4. McInnes IB et al. Upadacitinib in patients with psoriatic arthritis and an inadequate response to non-biological therapy: 56-week data from the phase 3 SELECT-PsA 1 study.  RMD Open. 2021;7:e001838 (Oct 18).
5. Christensen IE et al. Serious infections in patients with rheumatoid arthritis and psoriatic arthritis treated with tumour necrosis factor inhibitors: data from register linkage of the NOR-DMARD study. Ann Rheum Dis. 2021(Oct 8). Correction: Upadacitinib in patients with psoriatic arthritis and an inadequate response to non-biological therapy: 56-week data from the phase 3 SELECT-PsA 1 study. RMD Open. 2021 Nov;7(3):e001838corr1.

Research published in November has provided us with insights on the impact of psoriatic arthritis (PsA) as well as treatment outcomes. Although PsA often affects women of child-bearing age, data on pregnancy outcomes in PsA is scarce. To evaluate pregnancy outcomes in patients with severe PsA, Remaeus et al¹ conducted a Swedish nationwide register-based cohort study of births from Jul 1 2007 to Dec 31 2017. A total of 921 PsA- pregnancies and 9210 non-PsA-pregnancies (matched on maternal age, year, and parity) were identified. Pregnancy in PsA vs. non-PsA women were associated with increased risk for preterm birth (adjusted odds ratio [aOR] 1.69; 95% CI 1.27-2.24), elective cesarean delivery (CD; aOR 1.77; 95% CI 1.43-2.20), and emergency CD (aOR 1.42; 95% CI 1.10-1.84) with the risk even more pronounced in pregnancies in women with PsA with exposure to antirheumatic treatment any time before or during pregnancy (surrogate for disease severity- preterm birth: aOR 1.98; 95% CI 1.27-2.86; elective CD: aOR 1.96; 95% CI 1.47-2.63; and emergency CD: aOR 1.67; 95% CI 1.18-2.36). Thus, pregnant women with PsA, particularly those requiring antirheumatic treatment, are at increased risk for adverse pregnancy outcomes and therefore should be counselled appropriately.

Depression is a well-known comorbidity of PsA. However, little is known about the impact of the COVID-19 pandemic on the prevalence of depressive symptoms in PsA patients. Engelbrecht et al² evaluated 89 patients with PsA participating in the German multicenter RheumaDatenRhePort registry. Symptoms of depression were assessed using the Patient Health Questionnaire-2 (PHQ-2). The majority of patients scored <2 on the PHQ-2 indicating that they did not have depressive symptoms during (85.39%) and prior to (83.15%) the pandemic. The prevalence of depressive symptoms was not significantly different before and during the pandemic, irrespective of disease activity. Thus, contrary to expectations, the COVID-19 pandemic did not increase the occurrence of depressive symptoms among patients with PsA.

With regard to longer-term treatment efficacy and safety of recently approved advanced therapies for PsA, McInnes et al reported 2-year results from the from the Phase-3 DISCOVER-2 trial that included 739 biologic-naive patients with active PsA. At week 100, ACR20 response was achieved by 76%, 74%, and 68% of patients who initially were randomized to receive guselkumab every 4 weeks, every 8 weeks, or placebo, respectively, indicating a durable response. No new safety signals were identified. The 56-week efficacy and safety results from SELECT-PsA 1 trial with upadacitinib reported by McInnes et al^4,5 showed that of 1705 patients randomized, 1419 (83.2%) completed 56 weeks of treatment. A higher proportion of patients achieved ACR20 response with upadacitinib (15 mg, 74.4%; 30 mg, 74.7%) vs. adalimumab (68.5%; P = .046) at week 56. No new safety signals were identified.

Safety, especially risk of infection, remains a significant concern when treating patients with biologics, especially tumor necrosis factor inhibitors (TNFi). Patients with rheumatoid arthritis (RA) are known to have a higher risk of infection, but data are scarce regarding the risk of serious infections in patients with PsA treated with TNFi and the comparative risk of infection in TNFi-treated RA patients versus patients with PsA. Using data from 1,352 and 1,007 patients with RA and PsA, respectively, followed in the prospective multi-center NORwegian-Disease Modifying Anti-Rheumatic Drug (NOR-DMARD) registry, Christensen et al report that patients with PsA vs. RA had a lower risk of contracting serious infections (adjusted hazard ratio 0.65; P = .025).

References

1. Remaeus K et al. Pregnancy outcomes in women with psoriatic arthritis with respect to presence and timing of antirheumatic treatment. Arthritis Rheumatol. 2021(Oct 20).
2. Englbrecht M et al. Prevalence of depressive symptoms in patients with psoriatic arthritis: have numbers changed during the COVID-19 pandemic? Front Med (Lausanne). 2021(Nov 1);8:74826
3. McInnes IB et al. Long-term efficacy and safety of guselkumab, a monoclonal antibody specific to the p19 subunit of interleukin-23, through 2 years: results from a phase 3, randomized, double-blind, placebo-controlled study conducted in biologic-naïve patients with active psoriatic arthritis. Arthritis Rheumatol. 2021(Nov 1).
4. McInnes IB et al. Upadacitinib in patients with psoriatic arthritis and an inadequate response to non-biological therapy: 56-week data from the phase 3 SELECT-PsA 1 study.  RMD Open. 2021;7:e001838 (Oct 18).
5. Christensen IE et al. Serious infections in patients with rheumatoid arthritis and psoriatic arthritis treated with tumour necrosis factor inhibitors: data from register linkage of the NOR-DMARD study. Ann Rheum Dis. 2021(Oct 8). Correction: Upadacitinib in patients with psoriatic arthritis and an inadequate response to non-biological therapy: 56-week data from the phase 3 SELECT-PsA 1 study. RMD Open. 2021 Nov;7(3):e001838corr1.

The virtual elimination of Haemophilus influenzae type B as a respiratory pathogen, recognition of Mycoplasma  pneumoniae as a common cause of pneumonia in older children and young adults, and atypical pathogens in elderly adults have recently changed our selection of initial empiric antimicrobial therapy for lower respiratory tract infections in some patients. It is increasingly important to use such information since  narrow-spectrum antibiotics for empiric therapy of moderately severe community acquired pneumonia (CAP) should be standard therapy.¹ On the other hand, the addition of doxycycline to a beta-lactam antibiotic has recently been shown to improve outcomes of CAP in elderly adults.² Along with advanced age, male gender is also a risk factor for treatment failure of moderately severe CAP,³ so should be taken into consideration in management decisions.

If a patient with mild CAP does not respond to initial antibacterial therapy, the most likely explanation is a viral cause.  Other  bacterial causes might also be considered, such as Staphylococcus aureus, multi-resistant pneumococcus, coliforms, ampicillin-resistant H. influenzae, fungi, or anaerobes depending on clinical and laboratory factors.

New, rapid diagnostic tests are also useful in making clinical decisions and are particularly important for children who are unable to produce sputum for examination and whose small airways limit use of bronchoscopy. Recent studies have shown that heparin-binding protein (HBP) predicts disease progression in children with severe CAP, directing the physician to do further testing of microbiologic etiology.⁴

Treatment of pneumonia is usually empiric. If Chlamydia pneumoniae or M. pneumoniae is suspected as the responsible pathogen, azithromycin should be used as primary therapy. Quinolones or tetracycline-based antibiotics can be considered when macrolides are not tolerated. In children with community-acquired pneumonia (CAP) discharged from emergency departments or inpatient wards, findings from a trial including 814 children > 6 months old with CAP found that a lower dose and shorter course of amoxicillin was not inferior compared to higher doses and longer courses. The children were randomly assigned 1:1 after hospital discharge to receive one of the 4 possible combinations of amoxicillin dose (35-50 or 70-90 mg/kg) and duration (3 or 7 days). The results indicated that further outpatient treatment with amoxicillin at the lower dose was not inferior to a higher dose, and a 3-day treatment course was not inferior to a 7-day treatment course.⁵

Pneumococcal urinary antigen testing (PUAT) has recently been shown to direct narrow spectrum antibiotic therapy when positive in children or allow earlier de-escalation from broad spectrum antibiotics.⁶

When Staphylococcus aureus is suspected, methicillin resistance (MRSA) must be considered. Vancomycin has been standard therapy for this pathogen unless clindamycin susceptibility is documented. A recent study showed that the newer cephalosporin, ceftaroline, used as monotherapy or in combination with a macrolide or quinolone resulted in a lower hospital mortality rate than standard therapy with vancomycin or combination antibiotics.⁷

              Other data used to determine probable causes of CAP include associated clinical signs and symptoms, chest x-ray findings, and diagnostic laboratory tests. Sputum is rarely produced by children during episodes of pneumonia, so the usual common step in the management of adult severe pneumonias, Gram stain examination of sputum is eliminated.

              Antibiotics are selected primarily on the basis of age and severity of illness.  Duration of therapy is 7 to 10 days for uncomplicated CAP.  Once the causative agent is identified by culture or with one of the rapid antigen detection assays, specific therapy may be readily selected.

      Treatment of pneumonia is usually empiric but the preference for narrow spectrum antibiotics should be emphasized .¹  Amoxicillin for children and a quinolone for adults is the usual therapy.

      If a patient with mild CAP does not respond to initial antibacterial therapy, the most likely explanation is a viral cause but for severely ill patients, other bacterial etiologies should also be considered, particularly MRSA where the addition of caftaroline would be considered.⁷   

References

1. Schweitzer VA et al. Narrow-spectrum antibiotics for community-acquired pneumonia in Dutch adults (CAP-PACT): a cross-sectional, stepped-wedge, cluster-randomised, non-inferiority, antimicrobial stewardship intervention trial. Lancet Infect Dis. 2021(Oct 7).
2. Uddin M et al. Effectiveness of Beta-Lactam plus Doxycycline for Patients Hospitalized with Community-Acquired Pneumonia Clin Infect Dis. 2021;ciab863 (Nov 9).
3. Dinh A et al. Factors Associated With Treatment Failure in Moderately Severe Community-Acquired Pneumonia: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2021;4(10):e2129566 (Oct 15).
4. Huang C et al. Heparin-Binding Protein in Critically Ill Children With Severe Community-Acquired Pneumonia. Front Pediatr. 2021 (Oct 28).
5. Bielicki JA et al. Effect of Amoxicillin Dose and Treatment Duration on the Need for Antibiotic Re-treatment in Children With Community-Acquired Pneumonia: The CAP-IT Randomized Clinical Trial. JAMA. 2021;326(17):1713-1724 (Nov 2).
6. Greenfield A et al. Impact of Streptococcus pneumoniae Urinary Antigen Testing in Patients with Community-acquired Pneumonia Admitted within a Large Academic Health System. Open Forum Infect Dis. 2021;ofab522 (Oct 22).
7. Cilloniz C et al. Impact on in-hospital mortality of ceftaroline versus standard of care in community-acquired pneumonia: a propensity-matched analysis. Eur J Clin Microbiol Infect Dis. 2021 (Nov 12).

The virtual elimination of Haemophilus influenzae type B as a respiratory pathogen, recognition of Mycoplasma  pneumoniae as a common cause of pneumonia in older children and young adults, and atypical pathogens in elderly adults have recently changed our selection of initial empiric antimicrobial therapy for lower respiratory tract infections in some patients. It is increasingly important to use such information since  narrow-spectrum antibiotics for empiric therapy of moderately severe community acquired pneumonia (CAP) should be standard therapy.¹ On the other hand, the addition of doxycycline to a beta-lactam antibiotic has recently been shown to improve outcomes of CAP in elderly adults.² Along with advanced age, male gender is also a risk factor for treatment failure of moderately severe CAP,³ so should be taken into consideration in management decisions.

If a patient with mild CAP does not respond to initial antibacterial therapy, the most likely explanation is a viral cause.  Other  bacterial causes might also be considered, such as Staphylococcus aureus, multi-resistant pneumococcus, coliforms, ampicillin-resistant H. influenzae, fungi, or anaerobes depending on clinical and laboratory factors.

New, rapid diagnostic tests are also useful in making clinical decisions and are particularly important for children who are unable to produce sputum for examination and whose small airways limit use of bronchoscopy. Recent studies have shown that heparin-binding protein (HBP) predicts disease progression in children with severe CAP, directing the physician to do further testing of microbiologic etiology.⁴

Treatment of pneumonia is usually empiric. If Chlamydia pneumoniae or M. pneumoniae is suspected as the responsible pathogen, azithromycin should be used as primary therapy. Quinolones or tetracycline-based antibiotics can be considered when macrolides are not tolerated. In children with community-acquired pneumonia (CAP) discharged from emergency departments or inpatient wards, findings from a trial including 814 children > 6 months old with CAP found that a lower dose and shorter course of amoxicillin was not inferior compared to higher doses and longer courses. The children were randomly assigned 1:1 after hospital discharge to receive one of the 4 possible combinations of amoxicillin dose (35-50 or 70-90 mg/kg) and duration (3 or 7 days). The results indicated that further outpatient treatment with amoxicillin at the lower dose was not inferior to a higher dose, and a 3-day treatment course was not inferior to a 7-day treatment course.⁵

Pneumococcal urinary antigen testing (PUAT) has recently been shown to direct narrow spectrum antibiotic therapy when positive in children or allow earlier de-escalation from broad spectrum antibiotics.⁶

When Staphylococcus aureus is suspected, methicillin resistance (MRSA) must be considered. Vancomycin has been standard therapy for this pathogen unless clindamycin susceptibility is documented. A recent study showed that the newer cephalosporin, ceftaroline, used as monotherapy or in combination with a macrolide or quinolone resulted in a lower hospital mortality rate than standard therapy with vancomycin or combination antibiotics.⁷

              Other data used to determine probable causes of CAP include associated clinical signs and symptoms, chest x-ray findings, and diagnostic laboratory tests. Sputum is rarely produced by children during episodes of pneumonia, so the usual common step in the management of adult severe pneumonias, Gram stain examination of sputum is eliminated.

              Antibiotics are selected primarily on the basis of age and severity of illness.  Duration of therapy is 7 to 10 days for uncomplicated CAP.  Once the causative agent is identified by culture or with one of the rapid antigen detection assays, specific therapy may be readily selected.

      Treatment of pneumonia is usually empiric but the preference for narrow spectrum antibiotics should be emphasized .¹  Amoxicillin for children and a quinolone for adults is the usual therapy.

      If a patient with mild CAP does not respond to initial antibacterial therapy, the most likely explanation is a viral cause but for severely ill patients, other bacterial etiologies should also be considered, particularly MRSA where the addition of caftaroline would be considered.⁷   

References

1. Schweitzer VA et al. Narrow-spectrum antibiotics for community-acquired pneumonia in Dutch adults (CAP-PACT): a cross-sectional, stepped-wedge, cluster-randomised, non-inferiority, antimicrobial stewardship intervention trial. Lancet Infect Dis. 2021(Oct 7).
2. Uddin M et al. Effectiveness of Beta-Lactam plus Doxycycline for Patients Hospitalized with Community-Acquired Pneumonia Clin Infect Dis. 2021;ciab863 (Nov 9).
3. Dinh A et al. Factors Associated With Treatment Failure in Moderately Severe Community-Acquired Pneumonia: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2021;4(10):e2129566 (Oct 15).
4. Huang C et al. Heparin-Binding Protein in Critically Ill Children With Severe Community-Acquired Pneumonia. Front Pediatr. 2021 (Oct 28).
5. Bielicki JA et al. Effect of Amoxicillin Dose and Treatment Duration on the Need for Antibiotic Re-treatment in Children With Community-Acquired Pneumonia: The CAP-IT Randomized Clinical Trial. JAMA. 2021;326(17):1713-1724 (Nov 2).
6. Greenfield A et al. Impact of Streptococcus pneumoniae Urinary Antigen Testing in Patients with Community-acquired Pneumonia Admitted within a Large Academic Health System. Open Forum Infect Dis. 2021;ofab522 (Oct 22).
7. Cilloniz C et al. Impact on in-hospital mortality of ceftaroline versus standard of care in community-acquired pneumonia: a propensity-matched analysis. Eur J Clin Microbiol Infect Dis. 2021 (Nov 12).

The virtual elimination of Haemophilus influenzae type B as a respiratory pathogen, recognition of Mycoplasma  pneumoniae as a common cause of pneumonia in older children and young adults, and atypical pathogens in elderly adults have recently changed our selection of initial empiric antimicrobial therapy for lower respiratory tract infections in some patients. It is increasingly important to use such information since  narrow-spectrum antibiotics for empiric therapy of moderately severe community acquired pneumonia (CAP) should be standard therapy.¹ On the other hand, the addition of doxycycline to a beta-lactam antibiotic has recently been shown to improve outcomes of CAP in elderly adults.² Along with advanced age, male gender is also a risk factor for treatment failure of moderately severe CAP,³ so should be taken into consideration in management decisions.

If a patient with mild CAP does not respond to initial antibacterial therapy, the most likely explanation is a viral cause.  Other  bacterial causes might also be considered, such as Staphylococcus aureus, multi-resistant pneumococcus, coliforms, ampicillin-resistant H. influenzae, fungi, or anaerobes depending on clinical and laboratory factors.

New, rapid diagnostic tests are also useful in making clinical decisions and are particularly important for children who are unable to produce sputum for examination and whose small airways limit use of bronchoscopy. Recent studies have shown that heparin-binding protein (HBP) predicts disease progression in children with severe CAP, directing the physician to do further testing of microbiologic etiology.⁴

Treatment of pneumonia is usually empiric. If Chlamydia pneumoniae or M. pneumoniae is suspected as the responsible pathogen, azithromycin should be used as primary therapy. Quinolones or tetracycline-based antibiotics can be considered when macrolides are not tolerated. In children with community-acquired pneumonia (CAP) discharged from emergency departments or inpatient wards, findings from a trial including 814 children > 6 months old with CAP found that a lower dose and shorter course of amoxicillin was not inferior compared to higher doses and longer courses. The children were randomly assigned 1:1 after hospital discharge to receive one of the 4 possible combinations of amoxicillin dose (35-50 or 70-90 mg/kg) and duration (3 or 7 days). The results indicated that further outpatient treatment with amoxicillin at the lower dose was not inferior to a higher dose, and a 3-day treatment course was not inferior to a 7-day treatment course.⁵

Pneumococcal urinary antigen testing (PUAT) has recently been shown to direct narrow spectrum antibiotic therapy when positive in children or allow earlier de-escalation from broad spectrum antibiotics.⁶

When Staphylococcus aureus is suspected, methicillin resistance (MRSA) must be considered. Vancomycin has been standard therapy for this pathogen unless clindamycin susceptibility is documented. A recent study showed that the newer cephalosporin, ceftaroline, used as monotherapy or in combination with a macrolide or quinolone resulted in a lower hospital mortality rate than standard therapy with vancomycin or combination antibiotics.⁷

              Other data used to determine probable causes of CAP include associated clinical signs and symptoms, chest x-ray findings, and diagnostic laboratory tests. Sputum is rarely produced by children during episodes of pneumonia, so the usual common step in the management of adult severe pneumonias, Gram stain examination of sputum is eliminated.

              Antibiotics are selected primarily on the basis of age and severity of illness.  Duration of therapy is 7 to 10 days for uncomplicated CAP.  Once the causative agent is identified by culture or with one of the rapid antigen detection assays, specific therapy may be readily selected.

      Treatment of pneumonia is usually empiric but the preference for narrow spectrum antibiotics should be emphasized .¹  Amoxicillin for children and a quinolone for adults is the usual therapy.

      If a patient with mild CAP does not respond to initial antibacterial therapy, the most likely explanation is a viral cause but for severely ill patients, other bacterial etiologies should also be considered, particularly MRSA where the addition of caftaroline would be considered.⁷   

References

1. Schweitzer VA et al. Narrow-spectrum antibiotics for community-acquired pneumonia in Dutch adults (CAP-PACT): a cross-sectional, stepped-wedge, cluster-randomised, non-inferiority, antimicrobial stewardship intervention trial. Lancet Infect Dis. 2021(Oct 7).
2. Uddin M et al. Effectiveness of Beta-Lactam plus Doxycycline for Patients Hospitalized with Community-Acquired Pneumonia Clin Infect Dis. 2021;ciab863 (Nov 9).
3. Dinh A et al. Factors Associated With Treatment Failure in Moderately Severe Community-Acquired Pneumonia: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2021;4(10):e2129566 (Oct 15).
4. Huang C et al. Heparin-Binding Protein in Critically Ill Children With Severe Community-Acquired Pneumonia. Front Pediatr. 2021 (Oct 28).
5. Bielicki JA et al. Effect of Amoxicillin Dose and Treatment Duration on the Need for Antibiotic Re-treatment in Children With Community-Acquired Pneumonia: The CAP-IT Randomized Clinical Trial. JAMA. 2021;326(17):1713-1724 (Nov 2).
6. Greenfield A et al. Impact of Streptococcus pneumoniae Urinary Antigen Testing in Patients with Community-acquired Pneumonia Admitted within a Large Academic Health System. Open Forum Infect Dis. 2021;ofab522 (Oct 22).
7. Cilloniz C et al. Impact on in-hospital mortality of ceftaroline versus standard of care in community-acquired pneumonia: a propensity-matched analysis. Eur J Clin Microbiol Infect Dis. 2021 (Nov 12).

A second study answered a question I am often asked about neurological sequalae such as Guillain Barre syndrome among patients with COVID-19 infection, compared to risk of the same from vaccines. Patone et al linked country wide data from English National Immunisation (NIMS) Database of COVID-19 vaccinations with patient level data to examine incidence of neurological adverse events such acute central nervous system (CNS) demyelinating events, encephalitis meningitis and myelitis, Guillain–Barré syndrome, Bell’s palsy, myasthenic disorders, hemorrhagic stroke and subarachnoid hemorrhage in the 28 days following either having a positive SARS-CoV-2 test, or neither ChAdOx1nCoV-19 or BNT162b2 vaccines. The study reported increased incidence risk ratios (IRR) of hospitalization or death related to all of the aforementioned neurological events in patients with SARS-CoV-2 infection, particularly in the time right after diagnosis. There was a small increase in IRR for Guillain-Barre syndrome (IRR, 2.90; 95% confidence interval (CI): 2.15–3.92 at 15–21 days after vaccination) and Bell’s palsy (IRR, 1.29; 95% CI: 1.08–1.56 at 15–21 days) with ChAdOx1nCoV-19. However, this was lower than what was seen after a positive SARS-CoV-2 test (Guillain–Barré syndrome (IRR, 5.25; 95% CI: 3.00–9.18) and Bell’s Palsy, (IRR, 1.34; 95% CI: 0.91–1.97). There was a slightly increased association seen between hemorrhagic stroke and the first dose of BNT162b2, with IRR at 1–7 days (IRR, 1.27; 95% CI: 1.02–1.59) and 15–21 days (IRR, 1.38; 95% CI: 1.12–1.71). However, this risk was dwarfed compared to risk for hemorrhagic stroke seen up to 7 days after a positive SARS-CoV-2 test (IRR, 12.42; 95% CI: 7.73–19.95 at day 0; IRR, 2.01; 95% CI: 1.29–3.15 at 1–7 days). The results highlight immense increase of neurological events after SARS-CoV-2 infection.

Lastly, the RECOVERY trial reported out results of colchicine treatment arm, where 5,610 patients were assigned to standard of care (SOC) with colchicine compared to 5,730 who just received standard of care. The ongoing RECOVERY trial has been an incredibly power tool in helping identify both some effective treatments as well as shedding light on the limited utility of others. No significant differences were seen between the treatment and SOC only arms in all-cause mortality (rate ratio [RR], 1.01; P = .77),  the probability of being discharged alive within 28 days (RR, 0.98; P = .44), or the risk of progressing to invasive mechanical ventilation or death (RR, 1.02; P = .47). The large sample size as well as the well-controlled design provides good evidence that colchicine will not make the COVID-19 treatment arsenal.

A second study answered a question I am often asked about neurological sequalae such as Guillain Barre syndrome among patients with COVID-19 infection, compared to risk of the same from vaccines. Patone et al linked country wide data from English National Immunisation (NIMS) Database of COVID-19 vaccinations with patient level data to examine incidence of neurological adverse events such acute central nervous system (CNS) demyelinating events, encephalitis meningitis and myelitis, Guillain–Barré syndrome, Bell’s palsy, myasthenic disorders, hemorrhagic stroke and subarachnoid hemorrhage in the 28 days following either having a positive SARS-CoV-2 test, or neither ChAdOx1nCoV-19 or BNT162b2 vaccines. The study reported increased incidence risk ratios (IRR) of hospitalization or death related to all of the aforementioned neurological events in patients with SARS-CoV-2 infection, particularly in the time right after diagnosis. There was a small increase in IRR for Guillain-Barre syndrome (IRR, 2.90; 95% confidence interval (CI): 2.15–3.92 at 15–21 days after vaccination) and Bell’s palsy (IRR, 1.29; 95% CI: 1.08–1.56 at 15–21 days) with ChAdOx1nCoV-19. However, this was lower than what was seen after a positive SARS-CoV-2 test (Guillain–Barré syndrome (IRR, 5.25; 95% CI: 3.00–9.18) and Bell’s Palsy, (IRR, 1.34; 95% CI: 0.91–1.97). There was a slightly increased association seen between hemorrhagic stroke and the first dose of BNT162b2, with IRR at 1–7 days (IRR, 1.27; 95% CI: 1.02–1.59) and 15–21 days (IRR, 1.38; 95% CI: 1.12–1.71). However, this risk was dwarfed compared to risk for hemorrhagic stroke seen up to 7 days after a positive SARS-CoV-2 test (IRR, 12.42; 95% CI: 7.73–19.95 at day 0; IRR, 2.01; 95% CI: 1.29–3.15 at 1–7 days). The results highlight immense increase of neurological events after SARS-CoV-2 infection.

Lastly, the RECOVERY trial reported out results of colchicine treatment arm, where 5,610 patients were assigned to standard of care (SOC) with colchicine compared to 5,730 who just received standard of care. The ongoing RECOVERY trial has been an incredibly power tool in helping identify both some effective treatments as well as shedding light on the limited utility of others. No significant differences were seen between the treatment and SOC only arms in all-cause mortality (rate ratio [RR], 1.01; P = .77),  the probability of being discharged alive within 28 days (RR, 0.98; P = .44), or the risk of progressing to invasive mechanical ventilation or death (RR, 1.02; P = .47). The large sample size as well as the well-controlled design provides good evidence that colchicine will not make the COVID-19 treatment arsenal.

A second study answered a question I am often asked about neurological sequalae such as Guillain Barre syndrome among patients with COVID-19 infection, compared to risk of the same from vaccines. Patone et al linked country wide data from English National Immunisation (NIMS) Database of COVID-19 vaccinations with patient level data to examine incidence of neurological adverse events such acute central nervous system (CNS) demyelinating events, encephalitis meningitis and myelitis, Guillain–Barré syndrome, Bell’s palsy, myasthenic disorders, hemorrhagic stroke and subarachnoid hemorrhage in the 28 days following either having a positive SARS-CoV-2 test, or neither ChAdOx1nCoV-19 or BNT162b2 vaccines. The study reported increased incidence risk ratios (IRR) of hospitalization or death related to all of the aforementioned neurological events in patients with SARS-CoV-2 infection, particularly in the time right after diagnosis. There was a small increase in IRR for Guillain-Barre syndrome (IRR, 2.90; 95% confidence interval (CI): 2.15–3.92 at 15–21 days after vaccination) and Bell’s palsy (IRR, 1.29; 95% CI: 1.08–1.56 at 15–21 days) with ChAdOx1nCoV-19. However, this was lower than what was seen after a positive SARS-CoV-2 test (Guillain–Barré syndrome (IRR, 5.25; 95% CI: 3.00–9.18) and Bell’s Palsy, (IRR, 1.34; 95% CI: 0.91–1.97). There was a slightly increased association seen between hemorrhagic stroke and the first dose of BNT162b2, with IRR at 1–7 days (IRR, 1.27; 95% CI: 1.02–1.59) and 15–21 days (IRR, 1.38; 95% CI: 1.12–1.71). However, this risk was dwarfed compared to risk for hemorrhagic stroke seen up to 7 days after a positive SARS-CoV-2 test (IRR, 12.42; 95% CI: 7.73–19.95 at day 0; IRR, 2.01; 95% CI: 1.29–3.15 at 1–7 days). The results highlight immense increase of neurological events after SARS-CoV-2 infection.

Lastly, the RECOVERY trial reported out results of colchicine treatment arm, where 5,610 patients were assigned to standard of care (SOC) with colchicine compared to 5,730 who just received standard of care. The ongoing RECOVERY trial has been an incredibly power tool in helping identify both some effective treatments as well as shedding light on the limited utility of others. No significant differences were seen between the treatment and SOC only arms in all-cause mortality (rate ratio [RR], 1.01; P = .77),  the probability of being discharged alive within 28 days (RR, 0.98; P = .44), or the risk of progressing to invasive mechanical ventilation or death (RR, 1.02; P = .47). The large sample size as well as the well-controlled design provides good evidence that colchicine will not make the COVID-19 treatment arsenal.

Key clinical point: Development of bacteremia in immunocompetent adult patients managed in the ICU for severe pneumococcal community-acquired pneumonia (CAP) had no effect on mortality.

Main finding: In-hospital mortality (21.5% vs. 16.9%; P = .11) or baseline variables associated with in-hospital death, such as the age ≥65 years (P interaction = .45) and bilateral pulmonary infection (P interaction = .77), were not significantly different between patients with and without bacteremia.

Study details: This was a post hoc analysis of the prospective STREPTOGENE study including 614 immunocompetent adult white patients admitted to an ICU for severe pneumococcal CAP. Of these, 270 patients had a positive blood culture for Streptococcus pneumoniae at admission.

Disclosures: The study was sponsored by 2 public health care and research agencies: the Assistance Publique Hôpitaux de Paris and Délégation à la Recherche Clinique et au Développement. None of the authors declared any conflict of interests.

Source: Bellut H et al. Ann Intensive Care. 2021;11:148 (Oct 24). Doi: 10.1186/s13613-021-00936-z.

Key clinical point: Development of bacteremia in immunocompetent adult patients managed in the ICU for severe pneumococcal community-acquired pneumonia (CAP) had no effect on mortality.

Main finding: In-hospital mortality (21.5% vs. 16.9%; P = .11) or baseline variables associated with in-hospital death, such as the age ≥65 years (P interaction = .45) and bilateral pulmonary infection (P interaction = .77), were not significantly different between patients with and without bacteremia.

Study details: This was a post hoc analysis of the prospective STREPTOGENE study including 614 immunocompetent adult white patients admitted to an ICU for severe pneumococcal CAP. Of these, 270 patients had a positive blood culture for Streptococcus pneumoniae at admission.

Disclosures: The study was sponsored by 2 public health care and research agencies: the Assistance Publique Hôpitaux de Paris and Délégation à la Recherche Clinique et au Développement. None of the authors declared any conflict of interests.

Source: Bellut H et al. Ann Intensive Care. 2021;11:148 (Oct 24). Doi: 10.1186/s13613-021-00936-z.

Key clinical point: Development of bacteremia in immunocompetent adult patients managed in the ICU for severe pneumococcal community-acquired pneumonia (CAP) had no effect on mortality.

Main finding: In-hospital mortality (21.5% vs. 16.9%; P = .11) or baseline variables associated with in-hospital death, such as the age ≥65 years (P interaction = .45) and bilateral pulmonary infection (P interaction = .77), were not significantly different between patients with and without bacteremia.

Study details: This was a post hoc analysis of the prospective STREPTOGENE study including 614 immunocompetent adult white patients admitted to an ICU for severe pneumococcal CAP. Of these, 270 patients had a positive blood culture for Streptococcus pneumoniae at admission.

Disclosures: The study was sponsored by 2 public health care and research agencies: the Assistance Publique Hôpitaux de Paris and Délégation à la Recherche Clinique et au Développement. None of the authors declared any conflict of interests.

Source: Bellut H et al. Ann Intensive Care. 2021;11:148 (Oct 24). Doi: 10.1186/s13613-021-00936-z.

Key clinical point: Pneumococcal urinary antigen testing (PUAT) effectuated early de-escalation of broad-spectrum antibiotics among positive patients with community-acquired pneumonia (CAP) and thus should be widely performed to substantiate antimicrobial stewardship interventions.

Main finding: PUAT-positive patients showed a significantly shorter median (interquartile range) time to de-escalation vs. PUAT-negative patients (1 [0-2] days vs. 1 [1-2] days; P = .01) and a higher atypical (azithromycin or doxycycline) coverage discontinuation rate within 24 hours of PUAT (61.3% vs. 47.2%; P = .026), with no significant difference in methicillin-resistant Staphylococcus aureus agent discontinuation (P = .610) or antipseudomonal de-escalation (P = .895).

Study details: The data come from a retrospective chart review study including 910 adult patients who were hospitalized for CAP and, as part of the diagnostic procedure, underwent PUAT, which returned a positive result in 121 patients.

Disclosures: The authors reported no financial support or conflict of interests.

Source: Greenfield A et al. Open Forum Infect Dis. 2021;ofab522 (Oct 22). Doi: 10.1093/ofid/ofab522.

Key clinical point: Pneumococcal urinary antigen testing (PUAT) effectuated early de-escalation of broad-spectrum antibiotics among positive patients with community-acquired pneumonia (CAP) and thus should be widely performed to substantiate antimicrobial stewardship interventions.

Main finding: PUAT-positive patients showed a significantly shorter median (interquartile range) time to de-escalation vs. PUAT-negative patients (1 [0-2] days vs. 1 [1-2] days; P = .01) and a higher atypical (azithromycin or doxycycline) coverage discontinuation rate within 24 hours of PUAT (61.3% vs. 47.2%; P = .026), with no significant difference in methicillin-resistant Staphylococcus aureus agent discontinuation (P = .610) or antipseudomonal de-escalation (P = .895).

Study details: The data come from a retrospective chart review study including 910 adult patients who were hospitalized for CAP and, as part of the diagnostic procedure, underwent PUAT, which returned a positive result in 121 patients.

Disclosures: The authors reported no financial support or conflict of interests.

Source: Greenfield A et al. Open Forum Infect Dis. 2021;ofab522 (Oct 22). Doi: 10.1093/ofid/ofab522.

Key clinical point: Pneumococcal urinary antigen testing (PUAT) effectuated early de-escalation of broad-spectrum antibiotics among positive patients with community-acquired pneumonia (CAP) and thus should be widely performed to substantiate antimicrobial stewardship interventions.

Main finding: PUAT-positive patients showed a significantly shorter median (interquartile range) time to de-escalation vs. PUAT-negative patients (1 [0-2] days vs. 1 [1-2] days; P = .01) and a higher atypical (azithromycin or doxycycline) coverage discontinuation rate within 24 hours of PUAT (61.3% vs. 47.2%; P = .026), with no significant difference in methicillin-resistant Staphylococcus aureus agent discontinuation (P = .610) or antipseudomonal de-escalation (P = .895).

Study details: The data come from a retrospective chart review study including 910 adult patients who were hospitalized for CAP and, as part of the diagnostic procedure, underwent PUAT, which returned a positive result in 121 patients.

Disclosures: The authors reported no financial support or conflict of interests.

Source: Greenfield A et al. Open Forum Infect Dis. 2021;ofab522 (Oct 22). Doi: 10.1093/ofid/ofab522.