MDedge Rheumatology

Key clinical point: Combination of methotrexate (MTX) and leflunomide (LEF) had a good overall safety profile compared with MTX or LEF alone and other regimens involved in advanced therapy for rheumatoid arthritis (RA).

Major finding: The risk for serious adverse events (SAEs; adjusted hazard ratio, [aHR], 1.00; P = .984) was not higher; however, the risk for any adverse events (aHR, 1.22; P = .013) was higher with MTX+LEF vs. MTX or LEF alone. The risk for SAEs (aHR, 0.56; P = .011) and infectious SAEs (aHR, 0.48; P = .031) was lower with MTX+LEF combo vs. biologic disease-modifying antirheumatic drugs (bDMARD)/JAK inhibitor (JAKi) with MTX or LEF.

Study details: Findings are from an analysis of 1,671 patients with RA from BiobadaBrasil, a multicentric, observational study. Included patients initiated the first treatment course with a conventional synthetic-DMARD or first bDMARD/JAKi.

Disclosures: This study was funded by the Brazilian Society of Rheumatology with funds from various pharmaceutical companies marketing biological compounds. The authors declared no conflicts of interest.

Source: Bredemeier M et al. J Rheumatol. 2021 May 1. doi: 10.3899/jrheum.201248.

Key clinical point: Combination of methotrexate (MTX) and leflunomide (LEF) had a good overall safety profile compared with MTX or LEF alone and other regimens involved in advanced therapy for rheumatoid arthritis (RA).

Major finding: The risk for serious adverse events (SAEs; adjusted hazard ratio, [aHR], 1.00; P = .984) was not higher; however, the risk for any adverse events (aHR, 1.22; P = .013) was higher with MTX+LEF vs. MTX or LEF alone. The risk for SAEs (aHR, 0.56; P = .011) and infectious SAEs (aHR, 0.48; P = .031) was lower with MTX+LEF combo vs. biologic disease-modifying antirheumatic drugs (bDMARD)/JAK inhibitor (JAKi) with MTX or LEF.

Study details: Findings are from an analysis of 1,671 patients with RA from BiobadaBrasil, a multicentric, observational study. Included patients initiated the first treatment course with a conventional synthetic-DMARD or first bDMARD/JAKi.

Disclosures: This study was funded by the Brazilian Society of Rheumatology with funds from various pharmaceutical companies marketing biological compounds. The authors declared no conflicts of interest.

Source: Bredemeier M et al. J Rheumatol. 2021 May 1. doi: 10.3899/jrheum.201248.

Key clinical point: Combination of methotrexate (MTX) and leflunomide (LEF) had a good overall safety profile compared with MTX or LEF alone and other regimens involved in advanced therapy for rheumatoid arthritis (RA).

Major finding: The risk for serious adverse events (SAEs; adjusted hazard ratio, [aHR], 1.00; P = .984) was not higher; however, the risk for any adverse events (aHR, 1.22; P = .013) was higher with MTX+LEF vs. MTX or LEF alone. The risk for SAEs (aHR, 0.56; P = .011) and infectious SAEs (aHR, 0.48; P = .031) was lower with MTX+LEF combo vs. biologic disease-modifying antirheumatic drugs (bDMARD)/JAK inhibitor (JAKi) with MTX or LEF.

Study details: Findings are from an analysis of 1,671 patients with RA from BiobadaBrasil, a multicentric, observational study. Included patients initiated the first treatment course with a conventional synthetic-DMARD or first bDMARD/JAKi.

Disclosures: This study was funded by the Brazilian Society of Rheumatology with funds from various pharmaceutical companies marketing biological compounds. The authors declared no conflicts of interest.

Source: Bredemeier M et al. J Rheumatol. 2021 May 1. doi: 10.3899/jrheum.201248.

Key clinical point: Rheumatoid meningitis should be considered in adult patients with or without a diagnosis of rheumatoid arthritis (RA). This would help in timely diagnosis and treatment, thus improving its outcomes.

Major finding: Common clinical manifestations of rheumatoid meningitis were transient focal neurologic signs (64.28%), systemic symptoms (51.78%), episodic headaches (50.00%), and neuropsychiatric changes (47.32%). Brain imaging indicated frontal (82.69%) and parietal (77.88%) lobes as the most common lesion location. Laboratory findings included high levels of rheumatoid factor (89.71%), anticyclic citrulline peptide (89.47%), C-reactive protein (82.54%), and erythrocyte deposition rate (81.81%).

Study details: Findings are from a meta-analysis of 103 studies involving 130 cases of rheumatoid meningitis. RA was diagnosed previously in 83% of cases, whereas the remaining 17% of patients were diagnosed with RA during or after the first diagnosis of rheumatoid meningitis.

Disclosures: No outside funding was provided for this study. The authors did not report any conflicts of interest.

Source: Villa E et al. Eur J Neurol. 2021 May 9. doi: 10.1111/ene.14904.

Key clinical point: Rheumatoid meningitis should be considered in adult patients with or without a diagnosis of rheumatoid arthritis (RA). This would help in timely diagnosis and treatment, thus improving its outcomes.

Major finding: Common clinical manifestations of rheumatoid meningitis were transient focal neurologic signs (64.28%), systemic symptoms (51.78%), episodic headaches (50.00%), and neuropsychiatric changes (47.32%). Brain imaging indicated frontal (82.69%) and parietal (77.88%) lobes as the most common lesion location. Laboratory findings included high levels of rheumatoid factor (89.71%), anticyclic citrulline peptide (89.47%), C-reactive protein (82.54%), and erythrocyte deposition rate (81.81%).

Study details: Findings are from a meta-analysis of 103 studies involving 130 cases of rheumatoid meningitis. RA was diagnosed previously in 83% of cases, whereas the remaining 17% of patients were diagnosed with RA during or after the first diagnosis of rheumatoid meningitis.

Disclosures: No outside funding was provided for this study. The authors did not report any conflicts of interest.

Source: Villa E et al. Eur J Neurol. 2021 May 9. doi: 10.1111/ene.14904.

Key clinical point: Rheumatoid meningitis should be considered in adult patients with or without a diagnosis of rheumatoid arthritis (RA). This would help in timely diagnosis and treatment, thus improving its outcomes.

Major finding: Common clinical manifestations of rheumatoid meningitis were transient focal neurologic signs (64.28%), systemic symptoms (51.78%), episodic headaches (50.00%), and neuropsychiatric changes (47.32%). Brain imaging indicated frontal (82.69%) and parietal (77.88%) lobes as the most common lesion location. Laboratory findings included high levels of rheumatoid factor (89.71%), anticyclic citrulline peptide (89.47%), C-reactive protein (82.54%), and erythrocyte deposition rate (81.81%).

Study details: Findings are from a meta-analysis of 103 studies involving 130 cases of rheumatoid meningitis. RA was diagnosed previously in 83% of cases, whereas the remaining 17% of patients were diagnosed with RA during or after the first diagnosis of rheumatoid meningitis.

Disclosures: No outside funding was provided for this study. The authors did not report any conflicts of interest.

Source: Villa E et al. Eur J Neurol. 2021 May 9. doi: 10.1111/ene.14904.

Key clinical point: A recent large cohort of patients with early rheumatoid arthritis (RA) revealed favorable 10-year outcomes, significantly better than the outcomes observed in a previous cohort of patients studied in 1993.

Major finding: At 10 years, disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate remission, DAS28 sustained remission, and drug-free remission were achieved by 52.4%, 40.1%, and 14.1% of patients, respectively. Half of the patients did not have a serious functional disability. Mortality rates were lower than that in the 1993 cohort (4.5% vs. 11.0%) and similar to that in the general population.

Study details: The data come from an analysis of 521 patients from the ESPOIR cohort who were diagnosed with early arthritis between 2003 and 2005 with a probable or certain diagnosis of RA and had never been prescribed disease-modifying antirheumatic drugs or glucocorticoids.

Disclosures: This work was supported by the Merck Sharp and Dohme, INSERM, French Society of Rheumatology, AbbVie, Pfizer, Lilly, Fresenius, and Galapagos. The authors including the lead author reported receiving grants, consulting fees, speaker fees, and/or honoraria from various sources.

Source: Combe B et al. Rheumatology (Oxford). 2021 May 7. doi: 10.1093/rheumatology/keab398.

Key clinical point: A recent large cohort of patients with early rheumatoid arthritis (RA) revealed favorable 10-year outcomes, significantly better than the outcomes observed in a previous cohort of patients studied in 1993.

Major finding: At 10 years, disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate remission, DAS28 sustained remission, and drug-free remission were achieved by 52.4%, 40.1%, and 14.1% of patients, respectively. Half of the patients did not have a serious functional disability. Mortality rates were lower than that in the 1993 cohort (4.5% vs. 11.0%) and similar to that in the general population.

Study details: The data come from an analysis of 521 patients from the ESPOIR cohort who were diagnosed with early arthritis between 2003 and 2005 with a probable or certain diagnosis of RA and had never been prescribed disease-modifying antirheumatic drugs or glucocorticoids.

Disclosures: This work was supported by the Merck Sharp and Dohme, INSERM, French Society of Rheumatology, AbbVie, Pfizer, Lilly, Fresenius, and Galapagos. The authors including the lead author reported receiving grants, consulting fees, speaker fees, and/or honoraria from various sources.

Source: Combe B et al. Rheumatology (Oxford). 2021 May 7. doi: 10.1093/rheumatology/keab398.

Key clinical point: A recent large cohort of patients with early rheumatoid arthritis (RA) revealed favorable 10-year outcomes, significantly better than the outcomes observed in a previous cohort of patients studied in 1993.

Major finding: At 10 years, disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate remission, DAS28 sustained remission, and drug-free remission were achieved by 52.4%, 40.1%, and 14.1% of patients, respectively. Half of the patients did not have a serious functional disability. Mortality rates were lower than that in the 1993 cohort (4.5% vs. 11.0%) and similar to that in the general population.

Study details: The data come from an analysis of 521 patients from the ESPOIR cohort who were diagnosed with early arthritis between 2003 and 2005 with a probable or certain diagnosis of RA and had never been prescribed disease-modifying antirheumatic drugs or glucocorticoids.

Disclosures: This work was supported by the Merck Sharp and Dohme, INSERM, French Society of Rheumatology, AbbVie, Pfizer, Lilly, Fresenius, and Galapagos. The authors including the lead author reported receiving grants, consulting fees, speaker fees, and/or honoraria from various sources.

Source: Combe B et al. Rheumatology (Oxford). 2021 May 7. doi: 10.1093/rheumatology/keab398.

Key clinical point: Tofacitinib vs. tocilizumab was more likely to induce and maintain improvement in clinical disease activity index (CDAI) and remission during the first 12 months of therapy in biological disease-modifying antirheumatic drugs (bDMARD)-naïve patients with methotrexate-refractory rheumatoid arthritis (RA).

Major finding: Likelihood of achieving and maintaining 85% or more (adjusted odds ratio [aOR], 3.88; P less than .001), 70% or more (aOR, 2.89; P = .003) improvement in CDAI, and remission (aOR, 3.31; P less than .001) in the first 12 months was higher with tofacitinib vs. tocilizumab in bDMARD-naïve patients but not in patients with previous bDMARD failure.

Study details: This was a multicenter cohort study of 464 patients with methotrexate-refractory RA who had high to moderate CDAI and initiated treatment with tofacitinib (n=247) or tocilizumab (n=217).

Disclosures: This study was supported by research funds from the National Hospital Organization, Japan. The authors including the leading author reported receiving lecture fees from various sources.

Source: Mori S et al. RMD Open. 2021 May 6. doi: 10.1136/rmdopen-2021-001601.

Key clinical point: Tofacitinib vs. tocilizumab was more likely to induce and maintain improvement in clinical disease activity index (CDAI) and remission during the first 12 months of therapy in biological disease-modifying antirheumatic drugs (bDMARD)-naïve patients with methotrexate-refractory rheumatoid arthritis (RA).

Major finding: Likelihood of achieving and maintaining 85% or more (adjusted odds ratio [aOR], 3.88; P less than .001), 70% or more (aOR, 2.89; P = .003) improvement in CDAI, and remission (aOR, 3.31; P less than .001) in the first 12 months was higher with tofacitinib vs. tocilizumab in bDMARD-naïve patients but not in patients with previous bDMARD failure.

Study details: This was a multicenter cohort study of 464 patients with methotrexate-refractory RA who had high to moderate CDAI and initiated treatment with tofacitinib (n=247) or tocilizumab (n=217).

Disclosures: This study was supported by research funds from the National Hospital Organization, Japan. The authors including the leading author reported receiving lecture fees from various sources.

Source: Mori S et al. RMD Open. 2021 May 6. doi: 10.1136/rmdopen-2021-001601.

Key clinical point: Tofacitinib vs. tocilizumab was more likely to induce and maintain improvement in clinical disease activity index (CDAI) and remission during the first 12 months of therapy in biological disease-modifying antirheumatic drugs (bDMARD)-naïve patients with methotrexate-refractory rheumatoid arthritis (RA).

Major finding: Likelihood of achieving and maintaining 85% or more (adjusted odds ratio [aOR], 3.88; P less than .001), 70% or more (aOR, 2.89; P = .003) improvement in CDAI, and remission (aOR, 3.31; P less than .001) in the first 12 months was higher with tofacitinib vs. tocilizumab in bDMARD-naïve patients but not in patients with previous bDMARD failure.

Study details: This was a multicenter cohort study of 464 patients with methotrexate-refractory RA who had high to moderate CDAI and initiated treatment with tofacitinib (n=247) or tocilizumab (n=217).

Disclosures: This study was supported by research funds from the National Hospital Organization, Japan. The authors including the leading author reported receiving lecture fees from various sources.

Source: Mori S et al. RMD Open. 2021 May 6. doi: 10.1136/rmdopen-2021-001601.

Key clinical point: A 3-dose regimen of intravenous tranexamic acid (IV-TXA) was more effective than a single dose in reducing postoperative blood loss in patients with rheumatoid arthritis (RA) who underwent primary unilateral total knee arthroplasty (TKA).

Major finding: Decrease in total blood loss (P = .038), hidden blood loss (P = .036), and maximum hemoglobin drop (P less than .001) was significantly lower with 3 vs. a single dose of postoperative IV-TXA. Additionally, levels of D-dimer on postoperative day 1 were significantly lower with 3 vs. a single dose of IV-TXA (P less than .001). Incidences of thromboembolic events were similar between groups.

Study details: This was a single-center, randomized controlled trial of 104 patients who underwent primary unilateral TKA for RA and were randomly allocated to receive either a single dose of IV-TXA (1 g; n=52) 3 hours postoperatively or 3 doses of IV-TXA (1 g; n=52) 3, 6, and 12 hours postoperatively.

Disclosures: This study was supported by the Foundation of Health and Family planning Commission of Shanghai, China. The authors declared no conflicts of interest.

Source: Kang BX et al. BMC Musculoskelet Disord. 2021 May 7. doi: 10.1186/s12891-021-04307-4.

Key clinical point: A 3-dose regimen of intravenous tranexamic acid (IV-TXA) was more effective than a single dose in reducing postoperative blood loss in patients with rheumatoid arthritis (RA) who underwent primary unilateral total knee arthroplasty (TKA).

Major finding: Decrease in total blood loss (P = .038), hidden blood loss (P = .036), and maximum hemoglobin drop (P less than .001) was significantly lower with 3 vs. a single dose of postoperative IV-TXA. Additionally, levels of D-dimer on postoperative day 1 were significantly lower with 3 vs. a single dose of IV-TXA (P less than .001). Incidences of thromboembolic events were similar between groups.

Study details: This was a single-center, randomized controlled trial of 104 patients who underwent primary unilateral TKA for RA and were randomly allocated to receive either a single dose of IV-TXA (1 g; n=52) 3 hours postoperatively or 3 doses of IV-TXA (1 g; n=52) 3, 6, and 12 hours postoperatively.

Disclosures: This study was supported by the Foundation of Health and Family planning Commission of Shanghai, China. The authors declared no conflicts of interest.

Source: Kang BX et al. BMC Musculoskelet Disord. 2021 May 7. doi: 10.1186/s12891-021-04307-4.

Key clinical point: A 3-dose regimen of intravenous tranexamic acid (IV-TXA) was more effective than a single dose in reducing postoperative blood loss in patients with rheumatoid arthritis (RA) who underwent primary unilateral total knee arthroplasty (TKA).

Major finding: Decrease in total blood loss (P = .038), hidden blood loss (P = .036), and maximum hemoglobin drop (P less than .001) was significantly lower with 3 vs. a single dose of postoperative IV-TXA. Additionally, levels of D-dimer on postoperative day 1 were significantly lower with 3 vs. a single dose of IV-TXA (P less than .001). Incidences of thromboembolic events were similar between groups.

Study details: This was a single-center, randomized controlled trial of 104 patients who underwent primary unilateral TKA for RA and were randomly allocated to receive either a single dose of IV-TXA (1 g; n=52) 3 hours postoperatively or 3 doses of IV-TXA (1 g; n=52) 3, 6, and 12 hours postoperatively.

Disclosures: This study was supported by the Foundation of Health and Family planning Commission of Shanghai, China. The authors declared no conflicts of interest.

Source: Kang BX et al. BMC Musculoskelet Disord. 2021 May 7. doi: 10.1186/s12891-021-04307-4.

Key clinical point: Treatment with the half dose vs. stable dose of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was associated with increased rates of flares over 12 months in patients with rheumatoid arthritis (RA) in remission.

Major finding: At 12 months, the proportion of patients with at least 1 flare was significantly higher with half-dose vs. stable-dose csDMARDs (25% vs. 6%; risk difference, 18%; P = .003), thereby not meeting the noninferiority criterion of a 20% difference. There were 54 vs. 75 adverse events in the half-dose vs. stable-dose group.

Study details: Findings are from ARCTIC REWIND, a 36-month noninferiority trial of 160 patients with RA in remission for 12 months who were receiving stable csDMARDs. Patients were randomly allocated to either half-dose (n=80) or stable-dose (n=80) csDMARDs.

Disclosures: ARCTIC REWIND study was funded by the Research Council of Norway and South-Eastern Norway Regional Health Authority. The authors including the lead author reported receiving grants, personal fees, and nonfinancial support from various sources.

Source: Lillegraven S et al. JAMA. 2021 May 4. doi: 10.1001/jama.2021.4542.

Key clinical point: Treatment with the half dose vs. stable dose of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was associated with increased rates of flares over 12 months in patients with rheumatoid arthritis (RA) in remission.

Major finding: At 12 months, the proportion of patients with at least 1 flare was significantly higher with half-dose vs. stable-dose csDMARDs (25% vs. 6%; risk difference, 18%; P = .003), thereby not meeting the noninferiority criterion of a 20% difference. There were 54 vs. 75 adverse events in the half-dose vs. stable-dose group.

Study details: Findings are from ARCTIC REWIND, a 36-month noninferiority trial of 160 patients with RA in remission for 12 months who were receiving stable csDMARDs. Patients were randomly allocated to either half-dose (n=80) or stable-dose (n=80) csDMARDs.

Disclosures: ARCTIC REWIND study was funded by the Research Council of Norway and South-Eastern Norway Regional Health Authority. The authors including the lead author reported receiving grants, personal fees, and nonfinancial support from various sources.

Source: Lillegraven S et al. JAMA. 2021 May 4. doi: 10.1001/jama.2021.4542.

Key clinical point: Treatment with the half dose vs. stable dose of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was associated with increased rates of flares over 12 months in patients with rheumatoid arthritis (RA) in remission.

Major finding: At 12 months, the proportion of patients with at least 1 flare was significantly higher with half-dose vs. stable-dose csDMARDs (25% vs. 6%; risk difference, 18%; P = .003), thereby not meeting the noninferiority criterion of a 20% difference. There were 54 vs. 75 adverse events in the half-dose vs. stable-dose group.

Study details: Findings are from ARCTIC REWIND, a 36-month noninferiority trial of 160 patients with RA in remission for 12 months who were receiving stable csDMARDs. Patients were randomly allocated to either half-dose (n=80) or stable-dose (n=80) csDMARDs.

Disclosures: ARCTIC REWIND study was funded by the Research Council of Norway and South-Eastern Norway Regional Health Authority. The authors including the lead author reported receiving grants, personal fees, and nonfinancial support from various sources.

Source: Lillegraven S et al. JAMA. 2021 May 4. doi: 10.1001/jama.2021.4542.

Inhibiting granulocyte/macrophage–colony stimulating factor (GM-CSF) with mavrilimumab prevented some patients with severe COVID-19 pneumonia and hyperinflammation from needing mechanical ventilation and reduced their risk of dying versus placebo in a phase 2 study.

There was no difference in outcomes between the two doses of mavrilimumab used in the trial (6 mg/kg or 10 mg/kg) and combined data showed a higher percentage of patients achieving the primary endpoint of being alive and free of mechanical ventilation at 29 days, at 87%, versus placebo, at 74%.

The P value was 0.12, “which achieved the prespecified evidentiary standard of 0.2,” according to Lara Pupim, MD, vice president of clinical research and development at Kiniksa Pharmaceuticals in Lexington, Mass.

Importantly, there was a 61% reduction in the risk of dying if patients had received mavrilimumab rather than placebo, she reported at the annual European Congress of Rheumatology. Mortality at day 29 was 21% in the placebo arm but just 8% in the combined mavrilimumab arms (P = .07).

Hendrik Schulze-Koops, MD, called it a “surprising study” and that “the outcome is very spectacular” in his short appraisal of the study during the Clinical Highlights session on the final day of the congress.

Mavrilimumab was “a compound that we would not have thought that would have such an impact on the outcome of COVID-19 infected patients,” Dr. Schulze-Koops of Ludwig Maximilian University of Munich added.

In this small study, “there was a consistent suggestion of a biological effect across key endpoints,” Richard Conway, MBChB, PhD, a consultant rheumatologist at St. James’s Hospital in Dublin, pointed out in an interview.

“Similar to tocilizumab, the benefits with mavrilimumab appear to be in addition to those seen with glucocorticoids, as 96% of patients received dexamethasone,” Dr. Conway observed. Furthermore, nearly one-third received antiviral or remdesivir treatment.

“This study was likely underpowered to assess a clinically meaningful benefit,” he said, adding that “there is insufficient evidence at present to begin using mavrilimumab as an alternative to currently available agents.” That said, “these results are promising for future studies.”

Rationale for GM-CSF inhibition with mavrilimumab in COVID-19 pneumonia

“The cytokine GM-CSF is vital to both lung homeostasis and regulation of inflammation in autoimmunity,” Dr. Pupim explained.

She added that “GM-CSF is implicated in the mechanism of aberrant immune cell infiltration and activation in the lungs, and it may contribute to respiratory failure and death in patients with severe COVID-19 pneumonia and systemic hyperinflammation.”

The efficacy and safety of blocking GM-CSF with mavrilimumab have been shown previously in phase 2 studies in other diseases, Dr. Pupim noted. This includes patients with rheumatoid arthritis and those with giant cell arteritis.

“It was hypothesized that GM-CSF receptor–alpha blockade may reduce infiltration of pathogenic cells into the lung and may suppress inflammation in COVID-19 pneumonia in hyperinflammation,” she explained.

Study details and other outcome results

The study presented by Dr. Pupim was a phase 2/3 double-blind, placebo-controlled trial predominantly conducted in Brazil, the United States, and South Africa, with some participation in Peru and Chile.

Patients were eligible for inclusion if they had had a positive COVID-19 test within 14 days of randomization and had been hospitalized but not ventilated. Evidence of bilateral pneumonia on chest x-ray or CT scan and clinical laboratory evidence indicative of hyperinflammation were also prerequisites for study enrollment.

The ongoing study comprised two cohorts, Dr. Pupim explained: patients who have not been ventilated and those who have recently been ventilated. Dr. Pupim presented the data on the nonventilated cohort, noting that there was a total of 116 patients aged a mean of 57 years.

Patients were randomized to one of three treatment arms: two groups received a single intravenous infusion of mavrilimumab, either 6 mg/kg or 10 mg/kg, and the third group got a placebo.

“Using a time-to-event approach, looking at mechanical ventilation-free survival, mavrilimumab recipients experienced a 65% reduction in the risk of mechanical ventilation or death,” Dr. Pupim said (P = .0175).

“Separation in the Kaplan-Meier curves was evident very early after study drug administration,” she added.

There were trends toward a faster benefit with mavrilimumab than placebo in two other key secondary endpoints: the median time to achieving a two-point clinical improvement (7 vs. 11 days) and the median time to room air (7 vs. 9 days).

Timing of mavrilimumab administration and safety

Study coauthor and chief clinical development officer at Kiniksa, Arian Pano, MD, answered questions on the presentation. When asked about the timing of giving mavrilimumab, he said: “Based on these data it is before they go to ventilation, as soon as you have symptoms of hyperinflammation and a need for oxygen.”

Mavrilimumab is given as a single infusion “and has been well tolerated; virtually no interruptions occurred in this study.”

No serious adverse events related to mavrilimumab were seen, and adverse events, including secondary infections, which are known complications of COVID-19, occurred less frequently in mavrilimumab recipients, compared with placebo.

Dr. Pupim reported that there was a case of tuberculosis in one patient treated with mavrilimumab (10 mg/kg). That case had occurred in an “endemic area for tuberculosis,” and the patient had been screened before entry but only via a sputum sample.

“Prior to these events, the patient received high-dose corticosteroids, a known risk factor for reactivation of TB, and thus the potential additive contribution of mavrilimumab, if any, is uncertain.” Dr. Pupim said.

“Thrombotic events, another known complication of COVID-19, occurred in the placebo arm only,” she added.

Dr. Pano commented that the study has now “seamlessly continued to phase 3. So, basically, we did not stop the study. At the end of phase 2, we just locked the database and collected the data.” Both the 6 mg/kg and 10 mg/kg are being studied, but it’s “very likely [that] 6 mg/kg could be the dose that we may bring forward to the clinic in terms of registration, but that’s at this point in time. We will need to wait for the phase 3 data,” he observed. Those findings will hopefully be available later this year.

Kiniksa funded the study. Dr. Pupim, Dr. Pano, and multiple study coinvestigators are employees of the company.

Dr. Schulze-Koops was not involved in the study and had no specific disclosures. Dr. Conway had no financial disclosures to make in relation to his comments.

Inhibiting granulocyte/macrophage–colony stimulating factor (GM-CSF) with mavrilimumab prevented some patients with severe COVID-19 pneumonia and hyperinflammation from needing mechanical ventilation and reduced their risk of dying versus placebo in a phase 2 study.

There was no difference in outcomes between the two doses of mavrilimumab used in the trial (6 mg/kg or 10 mg/kg) and combined data showed a higher percentage of patients achieving the primary endpoint of being alive and free of mechanical ventilation at 29 days, at 87%, versus placebo, at 74%.

The P value was 0.12, “which achieved the prespecified evidentiary standard of 0.2,” according to Lara Pupim, MD, vice president of clinical research and development at Kiniksa Pharmaceuticals in Lexington, Mass.

Importantly, there was a 61% reduction in the risk of dying if patients had received mavrilimumab rather than placebo, she reported at the annual European Congress of Rheumatology. Mortality at day 29 was 21% in the placebo arm but just 8% in the combined mavrilimumab arms (P = .07).

Hendrik Schulze-Koops, MD, called it a “surprising study” and that “the outcome is very spectacular” in his short appraisal of the study during the Clinical Highlights session on the final day of the congress.

Mavrilimumab was “a compound that we would not have thought that would have such an impact on the outcome of COVID-19 infected patients,” Dr. Schulze-Koops of Ludwig Maximilian University of Munich added.

In this small study, “there was a consistent suggestion of a biological effect across key endpoints,” Richard Conway, MBChB, PhD, a consultant rheumatologist at St. James’s Hospital in Dublin, pointed out in an interview.

“Similar to tocilizumab, the benefits with mavrilimumab appear to be in addition to those seen with glucocorticoids, as 96% of patients received dexamethasone,” Dr. Conway observed. Furthermore, nearly one-third received antiviral or remdesivir treatment.

“This study was likely underpowered to assess a clinically meaningful benefit,” he said, adding that “there is insufficient evidence at present to begin using mavrilimumab as an alternative to currently available agents.” That said, “these results are promising for future studies.”

Rationale for GM-CSF inhibition with mavrilimumab in COVID-19 pneumonia

“The cytokine GM-CSF is vital to both lung homeostasis and regulation of inflammation in autoimmunity,” Dr. Pupim explained.

She added that “GM-CSF is implicated in the mechanism of aberrant immune cell infiltration and activation in the lungs, and it may contribute to respiratory failure and death in patients with severe COVID-19 pneumonia and systemic hyperinflammation.”

The efficacy and safety of blocking GM-CSF with mavrilimumab have been shown previously in phase 2 studies in other diseases, Dr. Pupim noted. This includes patients with rheumatoid arthritis and those with giant cell arteritis.

“It was hypothesized that GM-CSF receptor–alpha blockade may reduce infiltration of pathogenic cells into the lung and may suppress inflammation in COVID-19 pneumonia in hyperinflammation,” she explained.

Study details and other outcome results

The study presented by Dr. Pupim was a phase 2/3 double-blind, placebo-controlled trial predominantly conducted in Brazil, the United States, and South Africa, with some participation in Peru and Chile.

Patients were eligible for inclusion if they had had a positive COVID-19 test within 14 days of randomization and had been hospitalized but not ventilated. Evidence of bilateral pneumonia on chest x-ray or CT scan and clinical laboratory evidence indicative of hyperinflammation were also prerequisites for study enrollment.

The ongoing study comprised two cohorts, Dr. Pupim explained: patients who have not been ventilated and those who have recently been ventilated. Dr. Pupim presented the data on the nonventilated cohort, noting that there was a total of 116 patients aged a mean of 57 years.

Patients were randomized to one of three treatment arms: two groups received a single intravenous infusion of mavrilimumab, either 6 mg/kg or 10 mg/kg, and the third group got a placebo.

“Using a time-to-event approach, looking at mechanical ventilation-free survival, mavrilimumab recipients experienced a 65% reduction in the risk of mechanical ventilation or death,” Dr. Pupim said (P = .0175).

“Separation in the Kaplan-Meier curves was evident very early after study drug administration,” she added.

There were trends toward a faster benefit with mavrilimumab than placebo in two other key secondary endpoints: the median time to achieving a two-point clinical improvement (7 vs. 11 days) and the median time to room air (7 vs. 9 days).

Timing of mavrilimumab administration and safety

Study coauthor and chief clinical development officer at Kiniksa, Arian Pano, MD, answered questions on the presentation. When asked about the timing of giving mavrilimumab, he said: “Based on these data it is before they go to ventilation, as soon as you have symptoms of hyperinflammation and a need for oxygen.”

Mavrilimumab is given as a single infusion “and has been well tolerated; virtually no interruptions occurred in this study.”

No serious adverse events related to mavrilimumab were seen, and adverse events, including secondary infections, which are known complications of COVID-19, occurred less frequently in mavrilimumab recipients, compared with placebo.

Dr. Pupim reported that there was a case of tuberculosis in one patient treated with mavrilimumab (10 mg/kg). That case had occurred in an “endemic area for tuberculosis,” and the patient had been screened before entry but only via a sputum sample.

“Prior to these events, the patient received high-dose corticosteroids, a known risk factor for reactivation of TB, and thus the potential additive contribution of mavrilimumab, if any, is uncertain.” Dr. Pupim said.

“Thrombotic events, another known complication of COVID-19, occurred in the placebo arm only,” she added.

Dr. Pano commented that the study has now “seamlessly continued to phase 3. So, basically, we did not stop the study. At the end of phase 2, we just locked the database and collected the data.” Both the 6 mg/kg and 10 mg/kg are being studied, but it’s “very likely [that] 6 mg/kg could be the dose that we may bring forward to the clinic in terms of registration, but that’s at this point in time. We will need to wait for the phase 3 data,” he observed. Those findings will hopefully be available later this year.

Kiniksa funded the study. Dr. Pupim, Dr. Pano, and multiple study coinvestigators are employees of the company.

Dr. Schulze-Koops was not involved in the study and had no specific disclosures. Dr. Conway had no financial disclosures to make in relation to his comments.

Inhibiting granulocyte/macrophage–colony stimulating factor (GM-CSF) with mavrilimumab prevented some patients with severe COVID-19 pneumonia and hyperinflammation from needing mechanical ventilation and reduced their risk of dying versus placebo in a phase 2 study.

There was no difference in outcomes between the two doses of mavrilimumab used in the trial (6 mg/kg or 10 mg/kg) and combined data showed a higher percentage of patients achieving the primary endpoint of being alive and free of mechanical ventilation at 29 days, at 87%, versus placebo, at 74%.

The P value was 0.12, “which achieved the prespecified evidentiary standard of 0.2,” according to Lara Pupim, MD, vice president of clinical research and development at Kiniksa Pharmaceuticals in Lexington, Mass.

Importantly, there was a 61% reduction in the risk of dying if patients had received mavrilimumab rather than placebo, she reported at the annual European Congress of Rheumatology. Mortality at day 29 was 21% in the placebo arm but just 8% in the combined mavrilimumab arms (P = .07).

Hendrik Schulze-Koops, MD, called it a “surprising study” and that “the outcome is very spectacular” in his short appraisal of the study during the Clinical Highlights session on the final day of the congress.

Mavrilimumab was “a compound that we would not have thought that would have such an impact on the outcome of COVID-19 infected patients,” Dr. Schulze-Koops of Ludwig Maximilian University of Munich added.

In this small study, “there was a consistent suggestion of a biological effect across key endpoints,” Richard Conway, MBChB, PhD, a consultant rheumatologist at St. James’s Hospital in Dublin, pointed out in an interview.

“Similar to tocilizumab, the benefits with mavrilimumab appear to be in addition to those seen with glucocorticoids, as 96% of patients received dexamethasone,” Dr. Conway observed. Furthermore, nearly one-third received antiviral or remdesivir treatment.

“This study was likely underpowered to assess a clinically meaningful benefit,” he said, adding that “there is insufficient evidence at present to begin using mavrilimumab as an alternative to currently available agents.” That said, “these results are promising for future studies.”

Rationale for GM-CSF inhibition with mavrilimumab in COVID-19 pneumonia

“The cytokine GM-CSF is vital to both lung homeostasis and regulation of inflammation in autoimmunity,” Dr. Pupim explained.

She added that “GM-CSF is implicated in the mechanism of aberrant immune cell infiltration and activation in the lungs, and it may contribute to respiratory failure and death in patients with severe COVID-19 pneumonia and systemic hyperinflammation.”

The efficacy and safety of blocking GM-CSF with mavrilimumab have been shown previously in phase 2 studies in other diseases, Dr. Pupim noted. This includes patients with rheumatoid arthritis and those with giant cell arteritis.

“It was hypothesized that GM-CSF receptor–alpha blockade may reduce infiltration of pathogenic cells into the lung and may suppress inflammation in COVID-19 pneumonia in hyperinflammation,” she explained.

Study details and other outcome results

The study presented by Dr. Pupim was a phase 2/3 double-blind, placebo-controlled trial predominantly conducted in Brazil, the United States, and South Africa, with some participation in Peru and Chile.

Patients were eligible for inclusion if they had had a positive COVID-19 test within 14 days of randomization and had been hospitalized but not ventilated. Evidence of bilateral pneumonia on chest x-ray or CT scan and clinical laboratory evidence indicative of hyperinflammation were also prerequisites for study enrollment.

The ongoing study comprised two cohorts, Dr. Pupim explained: patients who have not been ventilated and those who have recently been ventilated. Dr. Pupim presented the data on the nonventilated cohort, noting that there was a total of 116 patients aged a mean of 57 years.

Patients were randomized to one of three treatment arms: two groups received a single intravenous infusion of mavrilimumab, either 6 mg/kg or 10 mg/kg, and the third group got a placebo.

“Using a time-to-event approach, looking at mechanical ventilation-free survival, mavrilimumab recipients experienced a 65% reduction in the risk of mechanical ventilation or death,” Dr. Pupim said (P = .0175).

“Separation in the Kaplan-Meier curves was evident very early after study drug administration,” she added.

There were trends toward a faster benefit with mavrilimumab than placebo in two other key secondary endpoints: the median time to achieving a two-point clinical improvement (7 vs. 11 days) and the median time to room air (7 vs. 9 days).

Timing of mavrilimumab administration and safety

Study coauthor and chief clinical development officer at Kiniksa, Arian Pano, MD, answered questions on the presentation. When asked about the timing of giving mavrilimumab, he said: “Based on these data it is before they go to ventilation, as soon as you have symptoms of hyperinflammation and a need for oxygen.”

Mavrilimumab is given as a single infusion “and has been well tolerated; virtually no interruptions occurred in this study.”

No serious adverse events related to mavrilimumab were seen, and adverse events, including secondary infections, which are known complications of COVID-19, occurred less frequently in mavrilimumab recipients, compared with placebo.

Dr. Pupim reported that there was a case of tuberculosis in one patient treated with mavrilimumab (10 mg/kg). That case had occurred in an “endemic area for tuberculosis,” and the patient had been screened before entry but only via a sputum sample.

“Prior to these events, the patient received high-dose corticosteroids, a known risk factor for reactivation of TB, and thus the potential additive contribution of mavrilimumab, if any, is uncertain.” Dr. Pupim said.

“Thrombotic events, another known complication of COVID-19, occurred in the placebo arm only,” she added.

Dr. Pano commented that the study has now “seamlessly continued to phase 3. So, basically, we did not stop the study. At the end of phase 2, we just locked the database and collected the data.” Both the 6 mg/kg and 10 mg/kg are being studied, but it’s “very likely [that] 6 mg/kg could be the dose that we may bring forward to the clinic in terms of registration, but that’s at this point in time. We will need to wait for the phase 3 data,” he observed. Those findings will hopefully be available later this year.

Kiniksa funded the study. Dr. Pupim, Dr. Pano, and multiple study coinvestigators are employees of the company.

Dr. Schulze-Koops was not involved in the study and had no specific disclosures. Dr. Conway had no financial disclosures to make in relation to his comments.

Pandemic smoking: More or less?

The COVID-19 pandemic has changed a lot of habits in people, for better or worse. Some people may have turned to food and alcohol for comfort, while others started on health kicks to emerge from the ordeal as new people. Well, the same can be said about smokers.

artisteer/Getty Images

New evidence comes from a survey conducted from May to July 2020 of 694 current and former smokers with an average age of 53 years. All had been hospitalized prior to the pandemic and had previously participated in clinical trials to for smoking cessation in Boston, Nashville, and Pittsburgh hospitals.

Researchers found that 32% of participants smoked more, 37% smoked less, and 31% made no change in their smoking habits. By the time of the survey, 28% of former smokers had relapsed. Although 68% of the participants believed smoking increased the risk of getting COVID-19, that still didn’t stop some people from smoking more. Why?

Respondents “might have increased their smoking due to stress and boredom. On the other hand, the fear of catching COVID might have led them to cut down or quit smoking,” said lead author Nancy A. Rigotti, MD. “Even before the pandemic, tobacco smoking was the leading preventable cause of death in the United States. COVID-19 has given smokers yet another good reason to stop smoking.”

This creates an opportunity for physicians to preach the gospel to smokers about their vulnerability to respiratory disease in hopes of getting them to quit for good. We just wish the same could be said for all of our excessive pandemic online shopping.
 

3,000 years and just one pair of genomes to wear

Men and women are different. We’ll give you a moment to pick your jaw off the ground.

It makes sense though, the sexes being different, especially when you look at the broader animal kingdom. The males and females of many species are slightly different when it comes to size and shape, but there’s a big question that literally only anthropologists have asked: Were human males and females more different in the past than they are today?

Leonard Mukooli/Pixabay

To be more specific, some scientists believe that males and females grew more similar when humans shifted from a hunter-gatherer lifestyle to a farming-based lifestyle, as agriculture encouraged a more equitable division of labor. Others believe that the differences come down to random chance.

Researchers from Penn State University analyzed genomic data from over 350,000 males and females stored in the UK Biobank and looked at the recent (within the last ~3,000 years; post-agriculture adoption in Britain) evolutionary histories of these loci. Height, body mass, hip circumference, body fat percentage, and waist circumference were analyzed, and while there were thousands of differences in the genomes, only one trait occurred more frequently during that time period: Females gained a significantly higher body fat content than males.

It’s a sad day then for the millions of people who were big fans of the “farming caused men and women to become more similar” theory. Count the LOTME crew among them. Be honest: Wouldn’t life be so much simpler if men and women were exactly the same? Just think about it, no more arguments about leaving the toilet seat up. It’d be worth it just for that.
 

Proteins don’t lie

Research published in Open Biology shows that the human brain contains 14,315 different proteins. The team conducting that study wanted to find out which organ was the most similar to the old brain box, so they did protein counts for the 32 other major tissue types, including heart, salivary gland, lung, spleen, and endometrium.

Gerd Altmann/Pixabay

The tissue with the most proteins in common with the center of human intelligence? You’re thinking it has to be colon at this point, right? We were sure it was going to be colon, but it’s not.

The winner, with 13,442 shared proteins, is the testes. The testes have 15,687 proteins, of which 85.7% are shared with the brain. The researchers, sadly, did not provide protein counts for the other tissue types, but we bet colon was a close second.
 

Dreaming about COVID?

We thought we were the only ones who have been having crazy dreams lately. Each one seems crazier and more vivid than the one before. Have you been having weird dreams lately?

Unsplash/@spanic

This is likely your brain’s coping mechanism to handle your pandemic stress, according to Dr. Erik Hoel of Tufts University. Dreams that are crazy and scary might make real life seem lighter and simpler. He calls it the “overfitted brain hypothesis.”

“It is their very strangeness that gives them their biological function,” Dr. Hoel said. It literally makes you feel like COVID-19 and lockdowns aren’t as scary as they seem.

We always knew our minds were powerful things. Apparently, your brain gets tired of everyday familiarity just like you do, and it creates crazy dreams to keep things interesting.

Just remember: That recurring dream that you’re back in college and missing 10 assignments is there to help you, not scare you! Even though it is pretty scary. 

Pandemic smoking: More or less?

The COVID-19 pandemic has changed a lot of habits in people, for better or worse. Some people may have turned to food and alcohol for comfort, while others started on health kicks to emerge from the ordeal as new people. Well, the same can be said about smokers.

artisteer/Getty Images

New evidence comes from a survey conducted from May to July 2020 of 694 current and former smokers with an average age of 53 years. All had been hospitalized prior to the pandemic and had previously participated in clinical trials to for smoking cessation in Boston, Nashville, and Pittsburgh hospitals.

Researchers found that 32% of participants smoked more, 37% smoked less, and 31% made no change in their smoking habits. By the time of the survey, 28% of former smokers had relapsed. Although 68% of the participants believed smoking increased the risk of getting COVID-19, that still didn’t stop some people from smoking more. Why?

Respondents “might have increased their smoking due to stress and boredom. On the other hand, the fear of catching COVID might have led them to cut down or quit smoking,” said lead author Nancy A. Rigotti, MD. “Even before the pandemic, tobacco smoking was the leading preventable cause of death in the United States. COVID-19 has given smokers yet another good reason to stop smoking.”

This creates an opportunity for physicians to preach the gospel to smokers about their vulnerability to respiratory disease in hopes of getting them to quit for good. We just wish the same could be said for all of our excessive pandemic online shopping.
 

3,000 years and just one pair of genomes to wear

Men and women are different. We’ll give you a moment to pick your jaw off the ground.

It makes sense though, the sexes being different, especially when you look at the broader animal kingdom. The males and females of many species are slightly different when it comes to size and shape, but there’s a big question that literally only anthropologists have asked: Were human males and females more different in the past than they are today?

Leonard Mukooli/Pixabay

To be more specific, some scientists believe that males and females grew more similar when humans shifted from a hunter-gatherer lifestyle to a farming-based lifestyle, as agriculture encouraged a more equitable division of labor. Others believe that the differences come down to random chance.

Researchers from Penn State University analyzed genomic data from over 350,000 males and females stored in the UK Biobank and looked at the recent (within the last ~3,000 years; post-agriculture adoption in Britain) evolutionary histories of these loci. Height, body mass, hip circumference, body fat percentage, and waist circumference were analyzed, and while there were thousands of differences in the genomes, only one trait occurred more frequently during that time period: Females gained a significantly higher body fat content than males.

It’s a sad day then for the millions of people who were big fans of the “farming caused men and women to become more similar” theory. Count the LOTME crew among them. Be honest: Wouldn’t life be so much simpler if men and women were exactly the same? Just think about it, no more arguments about leaving the toilet seat up. It’d be worth it just for that.
 

Proteins don’t lie

Research published in Open Biology shows that the human brain contains 14,315 different proteins. The team conducting that study wanted to find out which organ was the most similar to the old brain box, so they did protein counts for the 32 other major tissue types, including heart, salivary gland, lung, spleen, and endometrium.

Gerd Altmann/Pixabay

The tissue with the most proteins in common with the center of human intelligence? You’re thinking it has to be colon at this point, right? We were sure it was going to be colon, but it’s not.

The winner, with 13,442 shared proteins, is the testes. The testes have 15,687 proteins, of which 85.7% are shared with the brain. The researchers, sadly, did not provide protein counts for the other tissue types, but we bet colon was a close second.
 

Dreaming about COVID?

We thought we were the only ones who have been having crazy dreams lately. Each one seems crazier and more vivid than the one before. Have you been having weird dreams lately?

Unsplash/@spanic

This is likely your brain’s coping mechanism to handle your pandemic stress, according to Dr. Erik Hoel of Tufts University. Dreams that are crazy and scary might make real life seem lighter and simpler. He calls it the “overfitted brain hypothesis.”

“It is their very strangeness that gives them their biological function,” Dr. Hoel said. It literally makes you feel like COVID-19 and lockdowns aren’t as scary as they seem.

We always knew our minds were powerful things. Apparently, your brain gets tired of everyday familiarity just like you do, and it creates crazy dreams to keep things interesting.

Just remember: That recurring dream that you’re back in college and missing 10 assignments is there to help you, not scare you! Even though it is pretty scary. 

Pandemic smoking: More or less?

The COVID-19 pandemic has changed a lot of habits in people, for better or worse. Some people may have turned to food and alcohol for comfort, while others started on health kicks to emerge from the ordeal as new people. Well, the same can be said about smokers.

artisteer/Getty Images

New evidence comes from a survey conducted from May to July 2020 of 694 current and former smokers with an average age of 53 years. All had been hospitalized prior to the pandemic and had previously participated in clinical trials to for smoking cessation in Boston, Nashville, and Pittsburgh hospitals.

Researchers found that 32% of participants smoked more, 37% smoked less, and 31% made no change in their smoking habits. By the time of the survey, 28% of former smokers had relapsed. Although 68% of the participants believed smoking increased the risk of getting COVID-19, that still didn’t stop some people from smoking more. Why?

Respondents “might have increased their smoking due to stress and boredom. On the other hand, the fear of catching COVID might have led them to cut down or quit smoking,” said lead author Nancy A. Rigotti, MD. “Even before the pandemic, tobacco smoking was the leading preventable cause of death in the United States. COVID-19 has given smokers yet another good reason to stop smoking.”

This creates an opportunity for physicians to preach the gospel to smokers about their vulnerability to respiratory disease in hopes of getting them to quit for good. We just wish the same could be said for all of our excessive pandemic online shopping.
 

3,000 years and just one pair of genomes to wear

Men and women are different. We’ll give you a moment to pick your jaw off the ground.

It makes sense though, the sexes being different, especially when you look at the broader animal kingdom. The males and females of many species are slightly different when it comes to size and shape, but there’s a big question that literally only anthropologists have asked: Were human males and females more different in the past than they are today?

Leonard Mukooli/Pixabay

To be more specific, some scientists believe that males and females grew more similar when humans shifted from a hunter-gatherer lifestyle to a farming-based lifestyle, as agriculture encouraged a more equitable division of labor. Others believe that the differences come down to random chance.

Researchers from Penn State University analyzed genomic data from over 350,000 males and females stored in the UK Biobank and looked at the recent (within the last ~3,000 years; post-agriculture adoption in Britain) evolutionary histories of these loci. Height, body mass, hip circumference, body fat percentage, and waist circumference were analyzed, and while there were thousands of differences in the genomes, only one trait occurred more frequently during that time period: Females gained a significantly higher body fat content than males.

It’s a sad day then for the millions of people who were big fans of the “farming caused men and women to become more similar” theory. Count the LOTME crew among them. Be honest: Wouldn’t life be so much simpler if men and women were exactly the same? Just think about it, no more arguments about leaving the toilet seat up. It’d be worth it just for that.
 

Proteins don’t lie

Research published in Open Biology shows that the human brain contains 14,315 different proteins. The team conducting that study wanted to find out which organ was the most similar to the old brain box, so they did protein counts for the 32 other major tissue types, including heart, salivary gland, lung, spleen, and endometrium.

Gerd Altmann/Pixabay

The tissue with the most proteins in common with the center of human intelligence? You’re thinking it has to be colon at this point, right? We were sure it was going to be colon, but it’s not.

The winner, with 13,442 shared proteins, is the testes. The testes have 15,687 proteins, of which 85.7% are shared with the brain. The researchers, sadly, did not provide protein counts for the other tissue types, but we bet colon was a close second.
 

Dreaming about COVID?

We thought we were the only ones who have been having crazy dreams lately. Each one seems crazier and more vivid than the one before. Have you been having weird dreams lately?

Unsplash/@spanic

This is likely your brain’s coping mechanism to handle your pandemic stress, according to Dr. Erik Hoel of Tufts University. Dreams that are crazy and scary might make real life seem lighter and simpler. He calls it the “overfitted brain hypothesis.”

“It is their very strangeness that gives them their biological function,” Dr. Hoel said. It literally makes you feel like COVID-19 and lockdowns aren’t as scary as they seem.

We always knew our minds were powerful things. Apparently, your brain gets tired of everyday familiarity just like you do, and it creates crazy dreams to keep things interesting.

Just remember: That recurring dream that you’re back in college and missing 10 assignments is there to help you, not scare you! Even though it is pretty scary. 

In patients with rheumatoid arthritis, exposure to air pollution is associated with both elevated levels of C-reactive protein (CRP) and increased risk of arthritis flares, according to a novel longitudinal study presented at the annual European Congress of Rheumatology.

The data revealed “a striking association between air pollution and increased CRP levels and risk of an arthritis flare,” reported first author Giovanni Adami, MD, DSc, of the rheumatology unit at the University of Verona (Italy).

The excess risk of elevated CRP and flares began “at very low levels of exposure, even those below commonly used thresholds for risk to human health,” he added.
 

Study details

Researchers collected data on 888 patients with RA from numerous patient visits in the context of more than 13,000 air pollution records. The CRP levels and RA flares were evaluated in the context of air pollution monitoring that is performed on a daily basis at several sites in the city of Verona where the study was conducted. Verona is an industrial city in northern Italy that has high but variable levels of air pollution based on factory activity and weather conditions.

Patients with RA who provided clinical data for this study were matched by their proximity to specific air pollution monitoring sites. By linking CRP levels and disease activity to air pollution levels over multiple follow-up visits, the design allowed the RA study participants “to serve as their own controls,” Dr. Adami explained.

At each patient visit during the study, CRP levels were measured and disease activity assessed. Patients were considered to have elevated CRP when levels were 5 mg/L or higher. The presence of an RA flare was defined by a 1.2-point increase or more in 28-joint Disease Activity Score using CRP (DAS28-CRP).

Both the CRP level and the presence or absence of a flare were evaluated in relationship to the patient’s specific local air pollution levels in the prior 60 days.

Increased levels of CRP, a surrogate for inflammatory activity, and increased disease activity, were both associated with elevated exposure to air pollutants prior to an office visit. These associations remained statistically significant when evaluated by specific air pollutants such as carbon monoxide (CO), nitrogen oxides (NO₂, NO), small particulate matter (PM10; particles ≤ 10 mcm), and ozone (O₃).

The relationship between increased exposure to air pollution contaminants and elevated CRP was supported by a dose effect. In the case of PM10, for example, the odds ratio of having elevated CRP was increased by only about 25% (OR, 1.25) when mean levels were 30 mcg/m³ or lower in the period prior to the office visit. This rose incrementally for higher mean levels of PM10, reaching 70% (OR, 1.70) for levels > 50 mcg/m³.

The researchers detected statistically significant differences in mean and area-under-the curve (AUC) values of most air pollutants in the 60 days prior to office visits when patients had a flare versus when disease activity was low. For example, the difference in mean and AUC levels in the period prior to a flare relative to a period with low disease activity was significant for CO (P = .001 for both) and NO and NO₂ (P = .003 for both), and O₃ (P = .002 and P = .001, respectively). For PM10, P values were .011 and .005, respectively.

“Remarkably, we found that the cumulative exposure to NO₂ in the 60 days preceding a flare was approximately 500 mcg/m³ higher than the low disease activity visit, an exposure that equates to approximately 200 passively smoked cigarettes,” Dr. Adami reported.
 

Trying to confirm causality of association

Dr. Adami’s study is not the first study to link air pollution to risk of RA. Several have suggested that air pollution is a risk factor for developing joint disease, but a recently published study conducted in Kuwait associated greater disease activity with NO₂ and another air pollutant, sulfur dioxide (SO₂), although not CO, PM10, or O₃.

A coauthor of that study, which evaluated pollution in regard to disease activity on DAS score, Adeeba Al-Herz, MD, a rheumatology consultant at Al-Amiri Hospital, Kuwait City, said in an interview, “We proved the correlation between them but not the causality.”

However, she believes that this is an important area of inquiry.

“We are working now on another paper in which we studied a causal relationship between the two, meaning that we are evaluating whether SO₂ and NO₂ trigger RA activity,” Dr. Al-Herz said. That study is now complete, and the manuscript is being written.

The magnitude of the association in these two studies suggest that there might be a clinical message if causality can be confirmed, according to Dr. Adami. Although there are many reasons to seek to reduce and avoid air pollution, these data suggest risk of a proinflammatory state might be one of them.

Dr. Adami believes that the evidence of an adverse effect on patients with RA is strong.

“In order to reduce the burden of RA, public and environmental health policy makers should aim to diminish gaseous and particulate matter emissions to a larger extent than currently recommended,” he said.

In an interview after his presentation, Dr. Adami suggested that the risk of an inflammatory response and increases in arthritis flares from air pollution is not surprising. Previous studies have linked cigarette smoking to both.

“The mechanisms underlying the development of inflammation are very similar. Indeed, the toxic components contained in cigarette smoking are largely shared with diesel exhaust and fossil fuel combustion,” he said.

Although causality between air pollution and arthritis flares cannot be confirmed in these data, a basis for suspecting a causal relationship is supported by “plenty of in vitro and animal studies,” according to Dr. Adami.

On the basis of these studies, several mechanisms have been postulated.

“As an example, exposure to air pollution can promote the activation of the bronchus-associated lymphoid tissue (BALT), which can trigger the activation of the transcription factor nuclear factor-kappaB,” he said. This, in turn, can “lead to the secretion of proinflammatory cytokines, such as tumor necrosis factor–alpha and interleukin-1.”

Another theory is that posttranslational modification of proteins in the lung, a process called citrullination, “can lead to production of autoantibodies known to have a pathogenic role in RA,” he added.

Proving a causal relationship, however, is difficult.

“We certainly cannot conduct a randomized clinical trial on that and voluntarily expose some patients to pollution. Thus, we need to rely on observational data,” Dr. Adami said.

Of strategies being considered to generate evidence of a causal relationship between pollution and the exacerbation of RA, “we certainly will try to study those patients that move from a highly polluted area to a greener zone and vice versa,” he said. This will allow us “to explore what happens when the exposure to pollution changes dramatically in a short period of time.”

In the meantime, “given what is known to date, I would certainly advise my RA patients to avoid exposure to air pollution,” Dr. Adami said. He acknowledged there is no proof that this will help patients to reduce the risk of flares, but there are already many good reasons to minimize exposure to air pollution.

Dr. Adami and Dr. Al-Herz report no potential conflicts of interest.

In patients with rheumatoid arthritis, exposure to air pollution is associated with both elevated levels of C-reactive protein (CRP) and increased risk of arthritis flares, according to a novel longitudinal study presented at the annual European Congress of Rheumatology.

The data revealed “a striking association between air pollution and increased CRP levels and risk of an arthritis flare,” reported first author Giovanni Adami, MD, DSc, of the rheumatology unit at the University of Verona (Italy).

The excess risk of elevated CRP and flares began “at very low levels of exposure, even those below commonly used thresholds for risk to human health,” he added.
 

Study details

Researchers collected data on 888 patients with RA from numerous patient visits in the context of more than 13,000 air pollution records. The CRP levels and RA flares were evaluated in the context of air pollution monitoring that is performed on a daily basis at several sites in the city of Verona where the study was conducted. Verona is an industrial city in northern Italy that has high but variable levels of air pollution based on factory activity and weather conditions.

Patients with RA who provided clinical data for this study were matched by their proximity to specific air pollution monitoring sites. By linking CRP levels and disease activity to air pollution levels over multiple follow-up visits, the design allowed the RA study participants “to serve as their own controls,” Dr. Adami explained.

At each patient visit during the study, CRP levels were measured and disease activity assessed. Patients were considered to have elevated CRP when levels were 5 mg/L or higher. The presence of an RA flare was defined by a 1.2-point increase or more in 28-joint Disease Activity Score using CRP (DAS28-CRP).

Both the CRP level and the presence or absence of a flare were evaluated in relationship to the patient’s specific local air pollution levels in the prior 60 days.

Increased levels of CRP, a surrogate for inflammatory activity, and increased disease activity, were both associated with elevated exposure to air pollutants prior to an office visit. These associations remained statistically significant when evaluated by specific air pollutants such as carbon monoxide (CO), nitrogen oxides (NO₂, NO), small particulate matter (PM10; particles ≤ 10 mcm), and ozone (O₃).

The relationship between increased exposure to air pollution contaminants and elevated CRP was supported by a dose effect. In the case of PM10, for example, the odds ratio of having elevated CRP was increased by only about 25% (OR, 1.25) when mean levels were 30 mcg/m³ or lower in the period prior to the office visit. This rose incrementally for higher mean levels of PM10, reaching 70% (OR, 1.70) for levels > 50 mcg/m³.

The researchers detected statistically significant differences in mean and area-under-the curve (AUC) values of most air pollutants in the 60 days prior to office visits when patients had a flare versus when disease activity was low. For example, the difference in mean and AUC levels in the period prior to a flare relative to a period with low disease activity was significant for CO (P = .001 for both) and NO and NO₂ (P = .003 for both), and O₃ (P = .002 and P = .001, respectively). For PM10, P values were .011 and .005, respectively.

“Remarkably, we found that the cumulative exposure to NO₂ in the 60 days preceding a flare was approximately 500 mcg/m³ higher than the low disease activity visit, an exposure that equates to approximately 200 passively smoked cigarettes,” Dr. Adami reported.
 

Trying to confirm causality of association

Dr. Adami’s study is not the first study to link air pollution to risk of RA. Several have suggested that air pollution is a risk factor for developing joint disease, but a recently published study conducted in Kuwait associated greater disease activity with NO₂ and another air pollutant, sulfur dioxide (SO₂), although not CO, PM10, or O₃.

A coauthor of that study, which evaluated pollution in regard to disease activity on DAS score, Adeeba Al-Herz, MD, a rheumatology consultant at Al-Amiri Hospital, Kuwait City, said in an interview, “We proved the correlation between them but not the causality.”

However, she believes that this is an important area of inquiry.

“We are working now on another paper in which we studied a causal relationship between the two, meaning that we are evaluating whether SO₂ and NO₂ trigger RA activity,” Dr. Al-Herz said. That study is now complete, and the manuscript is being written.

The magnitude of the association in these two studies suggest that there might be a clinical message if causality can be confirmed, according to Dr. Adami. Although there are many reasons to seek to reduce and avoid air pollution, these data suggest risk of a proinflammatory state might be one of them.

Dr. Adami believes that the evidence of an adverse effect on patients with RA is strong.

“In order to reduce the burden of RA, public and environmental health policy makers should aim to diminish gaseous and particulate matter emissions to a larger extent than currently recommended,” he said.

In an interview after his presentation, Dr. Adami suggested that the risk of an inflammatory response and increases in arthritis flares from air pollution is not surprising. Previous studies have linked cigarette smoking to both.

“The mechanisms underlying the development of inflammation are very similar. Indeed, the toxic components contained in cigarette smoking are largely shared with diesel exhaust and fossil fuel combustion,” he said.

Although causality between air pollution and arthritis flares cannot be confirmed in these data, a basis for suspecting a causal relationship is supported by “plenty of in vitro and animal studies,” according to Dr. Adami.

On the basis of these studies, several mechanisms have been postulated.

“As an example, exposure to air pollution can promote the activation of the bronchus-associated lymphoid tissue (BALT), which can trigger the activation of the transcription factor nuclear factor-kappaB,” he said. This, in turn, can “lead to the secretion of proinflammatory cytokines, such as tumor necrosis factor–alpha and interleukin-1.”

Another theory is that posttranslational modification of proteins in the lung, a process called citrullination, “can lead to production of autoantibodies known to have a pathogenic role in RA,” he added.

Proving a causal relationship, however, is difficult.

“We certainly cannot conduct a randomized clinical trial on that and voluntarily expose some patients to pollution. Thus, we need to rely on observational data,” Dr. Adami said.

Of strategies being considered to generate evidence of a causal relationship between pollution and the exacerbation of RA, “we certainly will try to study those patients that move from a highly polluted area to a greener zone and vice versa,” he said. This will allow us “to explore what happens when the exposure to pollution changes dramatically in a short period of time.”

In the meantime, “given what is known to date, I would certainly advise my RA patients to avoid exposure to air pollution,” Dr. Adami said. He acknowledged there is no proof that this will help patients to reduce the risk of flares, but there are already many good reasons to minimize exposure to air pollution.

Dr. Adami and Dr. Al-Herz report no potential conflicts of interest.

In patients with rheumatoid arthritis, exposure to air pollution is associated with both elevated levels of C-reactive protein (CRP) and increased risk of arthritis flares, according to a novel longitudinal study presented at the annual European Congress of Rheumatology.

The data revealed “a striking association between air pollution and increased CRP levels and risk of an arthritis flare,” reported first author Giovanni Adami, MD, DSc, of the rheumatology unit at the University of Verona (Italy).

The excess risk of elevated CRP and flares began “at very low levels of exposure, even those below commonly used thresholds for risk to human health,” he added.
 

Study details

Researchers collected data on 888 patients with RA from numerous patient visits in the context of more than 13,000 air pollution records. The CRP levels and RA flares were evaluated in the context of air pollution monitoring that is performed on a daily basis at several sites in the city of Verona where the study was conducted. Verona is an industrial city in northern Italy that has high but variable levels of air pollution based on factory activity and weather conditions.

Patients with RA who provided clinical data for this study were matched by their proximity to specific air pollution monitoring sites. By linking CRP levels and disease activity to air pollution levels over multiple follow-up visits, the design allowed the RA study participants “to serve as their own controls,” Dr. Adami explained.

At each patient visit during the study, CRP levels were measured and disease activity assessed. Patients were considered to have elevated CRP when levels were 5 mg/L or higher. The presence of an RA flare was defined by a 1.2-point increase or more in 28-joint Disease Activity Score using CRP (DAS28-CRP).

Both the CRP level and the presence or absence of a flare were evaluated in relationship to the patient’s specific local air pollution levels in the prior 60 days.

Increased levels of CRP, a surrogate for inflammatory activity, and increased disease activity, were both associated with elevated exposure to air pollutants prior to an office visit. These associations remained statistically significant when evaluated by specific air pollutants such as carbon monoxide (CO), nitrogen oxides (NO₂, NO), small particulate matter (PM10; particles ≤ 10 mcm), and ozone (O₃).

The relationship between increased exposure to air pollution contaminants and elevated CRP was supported by a dose effect. In the case of PM10, for example, the odds ratio of having elevated CRP was increased by only about 25% (OR, 1.25) when mean levels were 30 mcg/m³ or lower in the period prior to the office visit. This rose incrementally for higher mean levels of PM10, reaching 70% (OR, 1.70) for levels > 50 mcg/m³.

The researchers detected statistically significant differences in mean and area-under-the curve (AUC) values of most air pollutants in the 60 days prior to office visits when patients had a flare versus when disease activity was low. For example, the difference in mean and AUC levels in the period prior to a flare relative to a period with low disease activity was significant for CO (P = .001 for both) and NO and NO₂ (P = .003 for both), and O₃ (P = .002 and P = .001, respectively). For PM10, P values were .011 and .005, respectively.

“Remarkably, we found that the cumulative exposure to NO₂ in the 60 days preceding a flare was approximately 500 mcg/m³ higher than the low disease activity visit, an exposure that equates to approximately 200 passively smoked cigarettes,” Dr. Adami reported.
 

Trying to confirm causality of association

Dr. Adami’s study is not the first study to link air pollution to risk of RA. Several have suggested that air pollution is a risk factor for developing joint disease, but a recently published study conducted in Kuwait associated greater disease activity with NO₂ and another air pollutant, sulfur dioxide (SO₂), although not CO, PM10, or O₃.

A coauthor of that study, which evaluated pollution in regard to disease activity on DAS score, Adeeba Al-Herz, MD, a rheumatology consultant at Al-Amiri Hospital, Kuwait City, said in an interview, “We proved the correlation between them but not the causality.”

However, she believes that this is an important area of inquiry.

“We are working now on another paper in which we studied a causal relationship between the two, meaning that we are evaluating whether SO₂ and NO₂ trigger RA activity,” Dr. Al-Herz said. That study is now complete, and the manuscript is being written.

The magnitude of the association in these two studies suggest that there might be a clinical message if causality can be confirmed, according to Dr. Adami. Although there are many reasons to seek to reduce and avoid air pollution, these data suggest risk of a proinflammatory state might be one of them.

Dr. Adami believes that the evidence of an adverse effect on patients with RA is strong.

“In order to reduce the burden of RA, public and environmental health policy makers should aim to diminish gaseous and particulate matter emissions to a larger extent than currently recommended,” he said.

In an interview after his presentation, Dr. Adami suggested that the risk of an inflammatory response and increases in arthritis flares from air pollution is not surprising. Previous studies have linked cigarette smoking to both.

“The mechanisms underlying the development of inflammation are very similar. Indeed, the toxic components contained in cigarette smoking are largely shared with diesel exhaust and fossil fuel combustion,” he said.

Although causality between air pollution and arthritis flares cannot be confirmed in these data, a basis for suspecting a causal relationship is supported by “plenty of in vitro and animal studies,” according to Dr. Adami.

On the basis of these studies, several mechanisms have been postulated.

“As an example, exposure to air pollution can promote the activation of the bronchus-associated lymphoid tissue (BALT), which can trigger the activation of the transcription factor nuclear factor-kappaB,” he said. This, in turn, can “lead to the secretion of proinflammatory cytokines, such as tumor necrosis factor–alpha and interleukin-1.”

Another theory is that posttranslational modification of proteins in the lung, a process called citrullination, “can lead to production of autoantibodies known to have a pathogenic role in RA,” he added.

Proving a causal relationship, however, is difficult.

“We certainly cannot conduct a randomized clinical trial on that and voluntarily expose some patients to pollution. Thus, we need to rely on observational data,” Dr. Adami said.

Of strategies being considered to generate evidence of a causal relationship between pollution and the exacerbation of RA, “we certainly will try to study those patients that move from a highly polluted area to a greener zone and vice versa,” he said. This will allow us “to explore what happens when the exposure to pollution changes dramatically in a short period of time.”

In the meantime, “given what is known to date, I would certainly advise my RA patients to avoid exposure to air pollution,” Dr. Adami said. He acknowledged there is no proof that this will help patients to reduce the risk of flares, but there are already many good reasons to minimize exposure to air pollution.

Dr. Adami and Dr. Al-Herz report no potential conflicts of interest.

A West Virginia physician faces up to 20 years in prison in the wake of his conviction by a federal jury for illegally distributing buprenorphine.

The jury convicted Sriramloo Kesari, MD, 78, of Charleston, for distributing buprenorphine outside the scope of medical practice, according to a U.S. Department of Justice statement. 

Investigators from the Drug Enforcement Administration presented evidence at the trial that Dr. Kesari, a general practitioner, operated a cash-only business selling buprenorphine prescriptions.

Federal prosecutors said that the physician signed prescriptions, which were then distributed by an employee in exchange for cash. Dr. Kesari was often absent, at times physically located in California, according to the federal government.

Prosecutors indicted the West Virginia physician in September 2019 as part of an “opioid strikeforce takedown” in Ohio, Virginia, and West Virginia that resulted in charges against 13 individuals, including 11 physicians.

Dr. Kesari’s attorneys filed motions during the course of the lengthy case showing that psychiatric and neurological exams indicated that the physician was cognitively impaired. 

Based on that evidence and the federal indictment, the West Virginia Board of Medicine suspended Dr. Kesari’s license in February 2020, stating that he is not “mentally and/or physically fit to practice medicine and surgery with reasonable skill and safety.”

Dr. Kesari was first licensed in West Virginia in 1979. In 1987, the Board of Medicine placed Dr. Kesari on a 3-year probation because of his failure to keep records for patients for whom he was prescribing controlled substances. 

However, within a few months, the Board changed the probation order to allow Dr. Kesari to write prescriptions for schedule II and III substances in the Boone Hospital emergency room where he continued to work.

The physician had no other disciplinary actions until his license suspension, but the Board lists settlement of four malpractice cases and the dismissal of a fifth between 1986 and 2001.

Dr. Kesari is scheduled to be sentenced on August 25.

A version of this article first appeared on Medscape.com.

A West Virginia physician faces up to 20 years in prison in the wake of his conviction by a federal jury for illegally distributing buprenorphine.

The jury convicted Sriramloo Kesari, MD, 78, of Charleston, for distributing buprenorphine outside the scope of medical practice, according to a U.S. Department of Justice statement. 

Investigators from the Drug Enforcement Administration presented evidence at the trial that Dr. Kesari, a general practitioner, operated a cash-only business selling buprenorphine prescriptions.

Federal prosecutors said that the physician signed prescriptions, which were then distributed by an employee in exchange for cash. Dr. Kesari was often absent, at times physically located in California, according to the federal government.

Prosecutors indicted the West Virginia physician in September 2019 as part of an “opioid strikeforce takedown” in Ohio, Virginia, and West Virginia that resulted in charges against 13 individuals, including 11 physicians.

Dr. Kesari’s attorneys filed motions during the course of the lengthy case showing that psychiatric and neurological exams indicated that the physician was cognitively impaired. 

Based on that evidence and the federal indictment, the West Virginia Board of Medicine suspended Dr. Kesari’s license in February 2020, stating that he is not “mentally and/or physically fit to practice medicine and surgery with reasonable skill and safety.”

Dr. Kesari was first licensed in West Virginia in 1979. In 1987, the Board of Medicine placed Dr. Kesari on a 3-year probation because of his failure to keep records for patients for whom he was prescribing controlled substances. 

However, within a few months, the Board changed the probation order to allow Dr. Kesari to write prescriptions for schedule II and III substances in the Boone Hospital emergency room where he continued to work.

The physician had no other disciplinary actions until his license suspension, but the Board lists settlement of four malpractice cases and the dismissal of a fifth between 1986 and 2001.

Dr. Kesari is scheduled to be sentenced on August 25.

A version of this article first appeared on Medscape.com.

A West Virginia physician faces up to 20 years in prison in the wake of his conviction by a federal jury for illegally distributing buprenorphine.

The jury convicted Sriramloo Kesari, MD, 78, of Charleston, for distributing buprenorphine outside the scope of medical practice, according to a U.S. Department of Justice statement. 

Investigators from the Drug Enforcement Administration presented evidence at the trial that Dr. Kesari, a general practitioner, operated a cash-only business selling buprenorphine prescriptions.

Federal prosecutors said that the physician signed prescriptions, which were then distributed by an employee in exchange for cash. Dr. Kesari was often absent, at times physically located in California, according to the federal government.

Prosecutors indicted the West Virginia physician in September 2019 as part of an “opioid strikeforce takedown” in Ohio, Virginia, and West Virginia that resulted in charges against 13 individuals, including 11 physicians.

Dr. Kesari’s attorneys filed motions during the course of the lengthy case showing that psychiatric and neurological exams indicated that the physician was cognitively impaired. 

Based on that evidence and the federal indictment, the West Virginia Board of Medicine suspended Dr. Kesari’s license in February 2020, stating that he is not “mentally and/or physically fit to practice medicine and surgery with reasonable skill and safety.”

Dr. Kesari was first licensed in West Virginia in 1979. In 1987, the Board of Medicine placed Dr. Kesari on a 3-year probation because of his failure to keep records for patients for whom he was prescribing controlled substances. 

However, within a few months, the Board changed the probation order to allow Dr. Kesari to write prescriptions for schedule II and III substances in the Boone Hospital emergency room where he continued to work.

The physician had no other disciplinary actions until his license suspension, but the Board lists settlement of four malpractice cases and the dismissal of a fifth between 1986 and 2001.

Dr. Kesari is scheduled to be sentenced on August 25.

A version of this article first appeared on Medscape.com.