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This article was originally published in NeurologyLive.

A recent study failed to show tumor necrosis factor receptor 1 (TNF-TNFR1) signaling inhibition can prevent or delay the risk or age at onset of Parkinson disease (PD).

Lead author Xioying Kang, MPH, BSc, department of medical epidemiology and biostatistics, Karolinka Institut, and colleagues found that TNF-TNFR1 signaling inhibition was not estimated to affect PD risk (odds ratio [OR] per 10% lower circulating C-reactive protein [CRP], 0.99; 95% CI, 0.91–1.08) or age at onset (0.13 years later onset; 95% CI, –0.66 to 0.92).

To the authors’ knowledge, this was the first Mendelian randomization (MR) study to address whether exposure to TNF inhibitors affect PD.

"Human genetics provides valuable guidance for therapeutic programs because the chances of successful drug development are substantially improved when genetic evidence links a drug’s target to an indication for therapeutic use,” Kang et al wrote. “Hence, our findings should be considered as part of discourse on the repurposing potential of TNF inhibitors for PD prevention and treatment, particularly if/when selective inhibitors of TNF-TNFR1 signaling become available.”

A total of 23 single nucleotide polymorphisms (SNPs) in the vicinity of the gene 

which encodes TNFR1, the principal effector of pro-inflammatory signaling following TNF agonism were present in the CRP data (genome-wide association studies [GWAS], n = 204,402).

The effects of TNF-TNFR1 inhibition were estimated for PD risk (Ncases/controls = 37,688/981,372) and age at PD onset (n = 28,568) using GWAS data from the International Parkinson’s Disease Genomics Consortium and 23andMe, Inc.

Researchers found, however, that genetically-indexed inhibition of TNF-TNFR1 signaling was predicted to reduce the risk of Crohn’s disease (OR, 0.75; 95% CI, 0.65–0.86) and ulcerative colitis (OR, 0.84; 95% CI, 0.74–0.97), and increased the risk of multiple sclerosis (MS; OR, 1.57; 95% CI, 1.36–1.81), as the authors noted was expected.

In secondary analyses, the more liberal linkage disequilibrium (LD) clumping yielded 4 correlated SNPs associated with CRP at false discovery rate-corrected (

<.05), 1 of which was not associated with either white blood cell count (WBC; 

The other 3 variants were associated with all 3 inflammatory markers for secondary MR models.

Using adapted inverse variance weighting (IVW) methodology to account for correlations between the variants, MR estimates based on the 3 SNPs remained consistent with the main results that neither PD risk nor age at onset were predicted to be affected by TNF-TNFR1 blockade.

Kang and colleagues also found that there were no associations of the genotypes of implicated functional variant (rs1800693) with PD risk (OR, 1.00 per TNF-inhibiting allele; 95% CI, 0.98–1.02) or age at onset (0.05 years of increase per TNF-inhibiting allele; 95% CI, –0.13 to 0.24), despite strong associations of this SNP with other inflammatory traits.

Tumor Necrosis Factor Inhibition and Parkinson Disease: A Mendelian Randomization Study

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Genetically-indexed inhibition of TNF-TNFR1 signaling was predicted to reduce the risk of Crohn’s disease and ulcerative colitis, and increased the risk of multiple sclerosis.

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TNF Treatment Fails to Prevent or Delay Parkinson Disease in Clinical Trial

While previous studies show albumin provides anti-inflammatory properties of 

 patients, there is a scarcity of larger clinical trials.

Whether targeting a serum albumin level of 30 g per liter or greater in this patient population with repeated daily infusions of 20% human albumin solution, compared to standard care, could reduce the incidences of infection, kidney dysfunction, and death is largely unknown.

A team, led by Louise China, PhD, Institute for Liver and Digestive Health, examined whether albumin is beneficial for hospitalized patients with decompensated cirrhosis who had a serum albumin level of less than 30 g per liter at enrollment.

In the randomized, multicenter, open-label, parallel-group trial, the investigators randomly assigned 777 patients to receive either targeted 20% human albumin solution for up to 14 days or until discharge or standard care.

Treatment commended within 3 days following admission.

Infection and increased systemic inflammation can cause organ dysfunction and death for patients with decompensated cirrhosis.

The investigators sought a composite primary endpoint of new infections, kidney dysfunction, or deaths between days 3-15 following treatment initiation.

The majority of patients in the study reported alcohol as the cause for cirrhosis.

A median total infusion of albumin of 200 g (interquartile range, 140-280) per patient was administered to the targeted albumin group (increasing the albumin level to ≥30 g per liter), as compared to a median of 20 g (interquartile range, 0-120) per patient administered to the standard-care group (adjusted mean difference, 143 g; 95% CI, 127-158.2).

Overall, the proportion of patients who met the primary endpoint did not significantly differ between the 2 groups.

In the targeted albumin group, 113 patients (29.7%) met the primary endpoint, while 120 individuals (30.2%) in the standard care group met the primary endpoint (aOR, 0.98; 95% CI, 0.71-1.33; 

In a time-to-event analysis where the researchers censored data at the time of discharge or at day 15, they found now significant between-group differences (HR, 1.04; 95% CI, 0.81-1.35).

In addition, more severe or life-threatening serious adverse events occurred in the albumin group than in the standard-care group.

“In patients hospitalized with decompensated cirrhosis, albumin infusions to increase the albumin level to a target of 30 g per liter or more was not more beneficial than the current standard care in the United Kingdom,” the authors wrote.

 might be especially beneficial for cirrhosis patients, reducing the risk of death.

The study, which was presented at Digestive Disease Week 2019 in San Diego, CA, found that physical activity was associated with a 73% lower risk of dying from liver disease after studying more than 117,000 people over a 26-year period.

While past studies and research have been limited, usually only assessing physical activity at one point or have had short follow-up periods. This study represented the first prospective study in a large US population to included updated measurements of physical activity over such a prolonged period. The longer study period allowed investigators to more accurately estimate the relationship between physical activity.

A Randomized Trial of Albumin Infusions in Hospitalized Patients with Cirrhosis

Albumin infusions did not result in statistically significant differences in predefined study endpoints.

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Albumin Treatment Not Necessarily Better for Cirrhosis Patients

 found that discordance in physician and patient disease severity assessments was associated with poorer mental health status.

“Although data are limited in psoriasis, studies have identified discordance between physician and patient measures of disease severity in chronic inflammatory diseases, for example, among one-third of patients with rheumatoid arthritis,” noted the study investigators.

Previous research has linked such discordance with patient dissatisfaction, lower treatment adherence, and worse disease outcomes. Therefore, the investigators indicated, it becomes necessary to evaluate potential underlying factors for these discrepancies so as to optimize care and shared decision-making.

A team led by Ewan Carr, PhD, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, evaluated psoriasis patients using self-assessment and clinical screening measures.

All patients had attended a large specialist service In London and Southeast England between May 12, 2016 — November 1, 2018. Data was analyzed between July 22 — October 22, 2019.

Carr and colleages evaluated 502 individuals, thus amounting to 1985 total observations.

Of the population, a majority were male (68%) and white individuals (79%). The mean age was 47 years.

On each visit, psoriasis severity was assessed using identifical patient and physician global assessment scales. Patients were asked to rate their disease severity on a 5-point scale, with 1 indicating clear/nearly clear and 5 indicating very clear.

Physicians rated patients on the same scale, and discordance was measured by substracting the patient assessment from the physician assessment. 

Psoriasis severity was also evaluated using the Psoriasis Area and Severity Index (PASI).

Furthermore, probable major depressive disorder was screened using the Patient Health Questionnaire-2 (PHQ-2) and PHQ-9. Probable generalized anxiety disorder was screened using the Generalized Anxiety Disorder scale (GAD-7).

Thus, 9% of patients screened positive for depression, and 10% screened positive for anxiety.

The investigators also noted physician-patient discordance in 39% of the 1985 office visits.

More specifically, patients rated their psoriasis as less severe on 26% of visits. Patients overestimated severity on 13% of visits.

Those who were considered positive for depression or anxiety were more likely to overestimate their psoriasis severity compared with their physician (relative risk ratio: depression, 2.7; 95% CI, 1.6-4.5; anxiety, 2.1; 95% CI, 1.3-3.4).

“These findings remained statistically significant after adjustment for age, ethnicity, sex, body mass index, smoking, number of comorbidities, treatment modality, and presence of psoriatic arthritis,” the investigators reported.

However, they qualified their findings by noting that patients with anxiety and depression and more severe psoriasis (PASI score > 10) were more likely more to underestimate their disease severity. 

Overestimation was more common if patients had PASI score ≤5.

“Thus, psoriasis severity may moderate the association of mental health status with patient-physician discordance,” Carr and team suggested.

The team acknowledged that their study did not account for stage of and experience with treatment regimens, which may have had an impact on mental health status. Furthermore, they believed that more work is needed to better understand what truly constitutes a meaningful level of discordance between patient and physician.

Nonetheless, they emphasized the implications of their findings, especially as they relate to addressing and screening for mental health in clinical practice. They encouraged the interpretation of patient-reported disease severity score in the context of comorbid anxiety and depression.

“The recognition, monitoring, and management of depression and anxiety in psoriasis by multidisciplinary health care teams (preferably encompassing clinical psychology expertise) has the potential to alleviate the substantial mental health burden in psoriasis while aligning clinician and patient perceptions of disease and treatment goals,” the investigators concluded.

Association of Patient Mental Health Status With the Level of Agreement Between Patient and Physician Ratings of Psoriasis Severity

The study underscores the importance of interpreting patient-reported disease severity scores in the context of mental health factors.


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Anxiety, Depression Linked to Patient Overestimation of Psoriasis Severity 

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 will achieve clinical remission and improvements treated with ABX464 when compared to placebo.

A team, led by Severine Vermeire, MD, PhD, Department of Gastroenterology, University Hospitals Leuven, recently presented data from an induction phase and open-label extension study showing the treatment results in primary endpoints and should be a candidate for later phase trials.

ABX464 is a novel, orally administrated small molecule that could treat ulcerative colitis by interacting with CBC, allowing specific splicing of anti-inflammatory miR-124, leading to a cascade of modulating pro-inflammatory cytokines. ABX464 has also demonstrated a dual mechanisms of action in HIV by generating miR-124 and splicing viral RNA that shows promise in its ability to treat inflammatory bowel disease (IBD).

The randomized study included both an 8-week placebo-controlled, double-blind induction period, as well as an open-label long-term extension phase involving adults as old as 75 years old with moderate to severe active ulcerative colitis.

The mean age of the induction phase was 43.3 years old, with 62.5% of the patient population being male.

The patients were randomized at a 2-1 ratio to receive either oral 50 mg ABX464 (n = 23) or placebo (n = 9) for 8 weeks in the induction phase.

The researchers sought primary endpoints of safety, assessed as the rate of
TEAEs and efficacy, which included the proportion of patients achieving clinical remission at week 8 compared to placebo, changes from baseline to week, Mayo Clinic Scores (MCS) and Partial Mayo Clinic Scores (pMCS), rates of endoscopic remission and improvement, changes from baseline to week 8 in (histopathological) Geboes score, change in fecal calprotectin, and miR-124 expression.

In the long-term extension phase, the researchers sought primary endpoints of the long-term safety of the treatment, and additional efficacy endpoints that included clinical and endoscopic rates of response and remission.

Of the 29 patients who completed the induction phase, 20 were in the treatment group. In addition, 22 of the 29 patients in the induction phase continued into the long-term extension trial.

Overall, 78.3% of the patients in the treatment group experienced adverse events, higher than the 55.6% of the placebo group that experienced an adverse event. The most common adverse events in the ABX464 arm of the study were abdominal pain and headache, both experienced by 17.4% of the patients.

In addition, 1 patient in the induction phase prematurely withdrew because of transaminase elevation 3x ULN. In addition, the most common adverse events through 24 months were nasopharyngitis and abdominal pain, each found in 31.3% of the treatment group.

Clinical remission was achieved by 35% of the treatment group patients at week 8, compared to just 11.1% of the placebo group.

For clinical response, 70% of the ABX464 group achieved this endpoint, which was also higher than the 33.3% of placebo patients that achieved a clinical response.

The researchers also found 50% and 10% of the treatment group achieved an endoscopic improvement and remission, respectively, compared to 11.1% each for the placebo group. For the 11 patients who achieved endoscopic improvement, all also showed histologic improvement.

“In conclusion, induction therapy with ABX464 50 mg QD appeared safe and well tolerated,” the authors wrote. “After 8 weeks of treatment, ABX464 appeared more effective than placebo in achieving endoscopic improvement and reduction of MCS and pMCS. Maintenance therapy with ABX464 sustained remission and brought additional patients into remission.”

Induction and long-term follow-up with ABX464

More patients also achieved endoscopic and histologic remission in the treatment group compared to the placebo group.

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ABX464 Results in Clinical Remission for Ulcerative Colitis Patients

Patients ≥65 years using glargine or detemir, rather than NPH insulin, had lower risk of hospitalizations or emergency department visits due to hypoglycemia. 

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Researchers see differences in how SARS-CoV-2 attacks the brain in comparison to the influenza virus that caused the 1918 pandemic. 

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Investigators noted a higher prevalence of nuclear sclerotic cataracts in infected patients versus uninfected patients.


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The immediate release d-MPH treatment is indicated for ADHD patients at least 6 years old. 

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Although overall decrease in mortality was similar to the control group, sickle cell populations were still less likely to receive a kidney transplant.  

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The FDA recently issued the third EUA for a COVID-19 vaccine in the US.

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A pooled analysis of sleep disturbance-related outcomes showed the IgE inhibitor significantly benefits a burdensome symptom of CRSwNP.

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Omalizumab Improves Sleep Outcomes with Nasal Polyposis Over 76 Weeks

From interpreting currently-understood risks to managing isolation-induced indoor allergen exposure, asthmatics may have concerns they address with clinicians.

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TNF Treatment Fails to Prevent or Delay Parkinson Disease in Clinical Trial

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Anxiety, Depression Linked to Patient Overestimation of Psoriasis Severity

Evaluation of Spinal Muscular Atrophy in the Era of Telehealth

ABX464 Results in Clinical Remission for Ulcerative Colitis Patients