fumaric acid

Caco-2 permeability of dimethylfumarate

increases

It also showed the highest permeability in the Caco-2 cell model

PMID:12973823 · one of two readings recorded this

intestinal permeability of monoesters versus lipophilicity

increases

The intestinal permeability of the monoesters methyl hydrogen fumarate, ethyl hydrogen fumarate, n-propylhydrogen fumarate and n-pentyl hydrogen fumarate increased with an increase in their lipophilicity

PMID:12973823 · one of two readings recorded this

presystemic metabolic lability of dimethylfumarate

increases

The uncharged diester dimethylfumarate displayed a high presystemic metabolic lability in all metabolism models

PMID:12973823 · one of two readings recorded this

presystemic metabolism rate of monoesters versus ester chain length

increases

their presystemic metabolism rates likewise increased with increasing ester chain length

PMID:12973823 · one of two readings recorded this

undegraded DMF on receiver side in Ussing-type chamber permeation

no effect

in permeation experiments with intestinal mucosa in Ussing-type chambers, no undegraded DMF was found on the receiver side, indicating complete metabolism in the intestinal tissue

PMID:12973823 · one of two readings recorded this

Cmax of monomethylfumarate, fasted vs fed

no effect, n = 10

The mean Cmax for monomethylfumarate in the blood of fasting subjects was to 0.84 mg l(-1) (range 0.37-1.29 mg l(-1); 95% CI 0.52, 1.07) and did not differ from that in fed subjects (0.48 mg l(-1); range 0-1.22 mg l(-1); 95% CI 0, 5.55)

PMID:15373936 · one of two readings recorded this

tlag of monomethylfumarate, fasted vs fed difference

decreases, n = 10

The tlag was 240 min [range 60-603 min; 95% confidence interval (CI) 139, 471] shorter when the tablet was taken after an overnight fast (90 min; range 60-120 min; 95% CI 66, 107) than when taken with breakfast (300 min; range 180-723 min; 95% CI 0, 1002)

PMID:15373936 · one of two readings recorded this

tmax of monomethylfumarate, fasted vs fed difference

decreases, n = 10

The tmax was 241 min (range 60-1189 min, 95% CI 53, 781) shorter when the tablet was taken after an overnight fast (182 min; range 120-240 min; 95% CI 146, 211) than when taken with breakfast (361 min; range 240-1429 min; 95% CI 0, 1062)

PMID:15373936 · one of two readings recorded this

half-life of DMF across media

half-life 12.72h in buffer (pH 7.4), 0.37h in serum, 0.10h in whole blood

The half-life of DMF in serum (Table 1 and Figure 1D) is dramatically shorter (p < 0.05) than that in a buffer of the same pH.

PMID:15479475 · one of two readings recorded this

hydrolysis of DMF to MMF by blood cell fraction

increases, monocytes/lymphocytes hydrolyzed DMF to MMF; granulocytes and erythrocytes did not

The results revealed that monocytes/lymphocytes, but not granulocytes and erythrocytes, at concentrations present in whole blood effectively hydrolyzed DMF to MMF.

PMID:15479475 · one of two readings recorded this

stability of MEF and MMF in acidic and alkaline buffers

no effect, MMF and MEF remained intact in buffers at pH 1 and pH 8 during the 6 h analysis period

Not recorded as a finding: confirms MEF and MMF do not themselves hydrolyse further; not a separate exposure or mechanism finding beyond the DMF-to-MMF conversion and MEF-does-not-alter-DMF-half-life claims already extracted

MMF remained intact in this buffer during the period of analysis (6 hr) as did MEF.

PMID:15479475 · one of two readings recorded this

enteric methane emissions in steers, respiration chambers with lasers and infrared gas analyzers

no effect, no effect of fumaric acid on methane emissions, p = 0.21

Not recorded as a finding: this platform holds no node for the endpoint

In Exp. 2, Procreatin-7 yeast (P = 0.72), Levucell SC yeast (P = 0.28), and fumaric acid (P = 0.21) had no effect on methane emissions, although emissions as a percentage of GE intake were 3% (non-significant, P = 0.39) less for steers fed Procreatin-7 yeast compared with the control.

PMID:15542482 · one of two readings recorded this

gross energy lost as methane, control diet

n = 16

Approximately 6.5% of the GE consumed was lost in the form of methane emissions from animals fed the control diet

PMID:15542482 · one of two readings recorded this

loss of GE to methane, corrected for energy intake

no effect, p = 0.09, n = 16

the loss of GE to methane was decreased by 21% (P = 0.002) using oil and by 9% (P = 0.09) using monensin

PMID:15542482 · one of two readings recorded this

loss of GE to methane, corrected for energy intake

decreases, p = 0.002, n = 16

the loss of GE to methane was decreased by 21% (P = 0.002) using oil and by 9% (P = 0.09) using monensin

PMID:15542482 · one of two readings recorded this

methane emissions as a percentage of GE intake

no effect, p = 0.39, n = 16

emissions as a percentage of GE intake were 3% (non-significant, P = 0.39) less for steers fed Procreatin-7 yeast compared with the control

PMID:15542482 · one of two readings recorded this

methane emissions

no effect, p = 0.21, n = 16

In Exp. 2, Procreatin-7 yeast (P = 0.72), Levucell SC yeast (P = 0.28), and fumaric acid (P = 0.21) had no effect on methane emissions

PMID:15542482 · one of two readings recorded this

methane emissions

no effect, p = 0.28, n = 16

In Exp. 2, Procreatin-7 yeast (P = 0.72), Levucell SC yeast (P = 0.28), and fumaric acid (P = 0.21) had no effect on methane emissions

PMID:15542482 · one of two readings recorded this

methane emissions

no effect, p = 0.44, n = 16

whereas monensin (P = 0.44) and enzyme had no effect (P = 0.82)

PMID:15542482 · one of two readings recorded this

methane emissions

no effect, p = 0.72, n = 16

In Exp. 2, Procreatin-7 yeast (P = 0.72), Levucell SC yeast (P = 0.28), and fumaric acid (P = 0.21) had no effect on methane emissions

PMID:15542482 · one of two readings recorded this

methane emissions

no effect, p = 0.82, n = 16

whereas monensin (P = 0.44) and enzyme had no effect (P = 0.82)

PMID:15542482 · one of two readings recorded this

methane emissions

decreases, p = 0.001, n = 16

In Exp. 1, sunflower oil decreased methane emissions by 22% (P = 0.001) compared with the control

PMID:15542482 · one of two readings recorded this

total-tract digestibility of NDF

decreases, p = 0.03, n = 16

oil decreased (P = 0.03) the total-tract digestibility of NDF by 20%

PMID:15542482 · one of two readings recorded this

astrocytic VEGF release and HIF-1α/Nrf2 activation in central nervous system cell types

increases

Not recorded as a finding: the trial gave a chemically different species

Here, we show that FAEs elicit HIF-1α accumulation, and VEGF release as its expected consequence, in astrocytes but not in other cell types of the central nervous system.

PMID:24098549 · one of two readings recorded this

HIF-1α protein accumulation in astrocytes

increases, increasing HIF-1α levels with DEF and DMF, transient, undetectable by 24h

Increasing levels of HIF-1α were observed with DEF and DMF.

PMID:24098549 · one of two readings recorded this

HIF-1α target gene GLUT1 mRNA expression in astrocytes and microglia exposed to FAEs

increases, FAEs induced VEGF and GLUT1 expression in astrocytes and microglia but not in neurons

Not recorded as a finding: gene-expression readout of the same HIF-1α pathway already captured at the protein/release level (HIF-1α accumulation and VEGF release extracted as mechanism claims)

In contrast FAEs induced the expression of VEGF and GLUT1, two HIF-1α targets in astrocytes and microglia but not in neurons.

PMID:24098549 · one of two readings recorded this

HIF-1alpha accumulation and VEGF release in astrocytes

increases

Not recorded as a finding: the trial gave a chemically different species

Here, we show that FAEs elicit HIF-1α accumulation, and VEGF release as its expected consequence, in astrocytes but not in other cell types of the central nervous system.

PMID:24098549 · one of two readings recorded this

Nrf2 protein levels in astrocytes

increases, increased upon DEF or DMF treatment

Consistent with previous studies, Nrf2 protein levels were increased upon both DEF or DMF treatments under the same experimental conditions, (Figure S1).

PMID:24098549 · one of two readings recorded this

VEGF and GLUT1 mRNA expression across CNS cell types

increases, induced in astrocytes and microglia but not neurons

In contrast FAEs induced the expression of VEGF and GLUT1, two HIF-1α targets in astrocytes and microglia but not in neurons.

PMID:24098549 · one of two readings recorded this

VEGF release from astrocytes

increases, strongly increased VEGF release into culture medium

Consistently, the application of both FAEs strongly increased the release of VEGF into the culture medium of primary astrocytes.

PMID:24098549 · one of two readings recorded this

Psoriasis Area and Severity Index (PASI) score

decreases, PASI score reduced from mean 21.57 to 10.77 with FAE after 16 weeks, unchanged with placebo

Not recorded as a finding: this platform holds no node for the endpoint

Altmeyer et al. 16 reported a reduction of PASI score from a mean of 21·57 at baseline to 10·77 after 16 weeks of FAE treatment, whereas in the placebo group it remained the same (P < 0·001).

PMID:27087044 · one of two readings recorded this

dropout due to adverse effects vs placebo

no effect, 2/13 FAE vs 0/14 placebo, RR 5.36 (0.28-102.12), n = 27

In this study, two withdrawals occurred in the FAE group (n = 13) compared with no dropouts in the placebo arm (n = 14) (RR 5·36, 95% CI 0·28–102·12; 27 participants; very low‐quality evidence).

PMID:27087044 · one of two readings recorded this

Dropout due to adverse effects

no effect, n = 27

There was no difference in dropout rates due to adverse effects (RR 5·36, 95% CI 0·28-102·12; one study; 27 participants; very low-quality evidence and wide CI)

PMID:27087044 · one of two readings recorded this

Nuisance adverse effects

increases, n = 99

More participants experienced nuisance adverse effects with FAEs (76%) than with placebo (16%) (RR 4·72, 95% CI 2·45-9·08; one study; 99 participants; moderate-quality evidence)

PMID:27087044 · one of two readings recorded this

PASI 50 response

increases, n = 247

PASI 50 response after 12-16 weeks, which was achieved by 64% of participants on FAEs compared with 14% on placebo: risk ratio (RR) 4·55, 95% confidence interval (CI) 2·80-7·40

PMID:27087044 · one of two readings recorded this

PASI score at follow-up vs methotrexate

no effect, significant difference favouring methotrexate at week 12 follow-up, MD 3.80 (0.68-6.92)

However, when we compared the PASI scores at follow‐up (week 12), as recommended by The Cochrane Collaboration, there was a significant difference in favour of methotrexate (MD 3·80, 95% CI 0·68–6·92; very low‐quality evidence).

PMID:27087044 · one of two readings recorded this

PASI score vs placebo

decreases, reduced from mean 21.57 to 10.77 with FAE vs unchanged with placebo

Altmeyer et al. 16 reported a reduction of PASI score from a mean of 21·57 at baseline to 10·77 after 16 weeks of FAE treatment, whereas in the placebo group it remained the same (P < 0·001).

PMID:27087044 · one of two readings recorded this

quality of life, Skindex-29

decreases, score fell from 54.7 to 27.0 with FAE vs 54.0 to 51.1 with placebo, between-group difference -19.3 points

The mean score in the FAE group decreased from 54·7 at baseline to 27·0 at week 16, in comparison with a reduction from 54·0 to 51·1 in the placebo arm, a between‐group difference of −19·3 points (P < 0·001).

PMID:27087044 · one of two readings recorded this

itaconic acid yield

an IA yield of 0.14% was obtained by LSF of corn cob hydrolysates by A. oryzae

PMID:27291673 · one of two readings recorded this

maximum fumaric acid yield

increases

The maximum FA yield was obtained when A. terreus was used for LSF of corn cob hydrolysate (1.9% total glucose)

PMID:27291673 · one of two readings recorded this

CD4+ and CD8+ cell counts, and lymphocyte and leukocyte counts, before versus during fumaric acid ester therapy in psoriasis patients, single cohort with no control arm

decreases, CD4+ reduced about 30.2%, CD8+ about 45.3%

Not recorded as a finding: the result compares a group with itself, not with a control

The CD4+ and CD8+ cell counts were significantly reduced by about 30.2 and 45.3%, respectively.

PMID:28954274 · one of two readings recorded this

CD4+ and CD8+ cell counts and lymphocyte count during fumaric acid ester therapy in psoriasis

decreases, CD4+ and CD8+ counts reduced by about 30.2 and 45.3%

Not recorded as a finding: the result compares a group with itself, not with a control

The CD4+ and CD8+ cell counts were significantly reduced by about 30.2 and 45.3%, respectively.

PMID:28954274 · one of two readings recorded this

CD4+ cell count reduction

decreases, n = 36

The CD4+ and CD8+ cell counts were significantly reduced by about 30.2 and 45.3%, respectively

PMID:28954274 · one of two readings recorded this

CD8+ cell count reduction

decreases, n = 36

The CD4+ and CD8+ cell counts were significantly reduced by about 30.2 and 45.3%, respectively

PMID:28954274 · one of two readings recorded this

median lymphocyte count reduction

decreases, n = 105

The median lymphocyte count was significantly reduced by about 35.8% after the first 6 months of therapy

PMID:28954274 · one of two readings recorded this

patients developing lymphopenia at lymphocyte count nadir

increases, n = 105

When assessing the lymphocyte count nadir over the whole period observed, 46.7% of the patients developed lymphopenia

PMID:28954274 · one of two readings recorded this

patients with severe lymphopenia (<500/µL)

increases, n = 105

Severe lymphopenia (<500/µL) was documented in 11.4% of the patients

PMID:28954274 · one of two readings recorded this

Tenofovir AUC0-t, geometric mean ratio of DA-2802 to TDF

no effect, n = 32

The geometric mean ratio (90% CI) of DA-2802 to TDF was 0.898 (0.815-0.990) for Cmax and 0.904 (0.836-0.978) for AUC0-t

PMID:29158663 · one of two readings recorded this

Tenofovir Cmax, geometric mean ratio of DA-2802 to TDF

no effect, n = 32

The geometric mean ratio (90% CI) of DA-2802 to TDF was 0.898 (0.815-0.990) for Cmax and 0.904 (0.836-0.978) for AUC0-t

PMID:29158663 · one of two readings recorded this

Adverse events leading to treatment discontinuation

n = 859

Adverse events leading to treatment discontinuation were observed in 12.9% of patients

PMID:29705996 · one of two readings recorded this

Median time to cumulative PASI 75 response rate of 50%

achieved in the FAE monotherapy subcohort after a median of 3 years of treatment

PMID:29705996 · one of two readings recorded this

Median time to cumulative PASI 75 response rate of 50%

p = 0.001

in the FAEs + phototherapy subcohort after 6.7 years and in the FAEs + methotrexate subcohort after 8.1 years (P = 0.001)

PMID:29705996 · one of two readings recorded this

Median time to cumulative PASI 75 response rate of 50%

p = 0.001

in the FAEs + phototherapy subcohort after 6.7 years and in the FAEs + methotrexate subcohort after 8.1 years (P = 0.001)

PMID:29705996 · one of two readings recorded this

Median time to cumulative sPGA response rate of 50% (light and at least 2-point reduction)

no effect, p = 0.7

A median duration of 1 year was observed in all three treatment subcohorts (P = 0.70)

PMID:29705996 · one of two readings recorded this

Patients reporting adverse events

n = 859

Approximately half of patients (49.0%) reported adverse events (566 total events)

PMID:29705996 · one of two readings recorded this

Patients with serious adverse events

n = 859

Serious adverse events were reported in 2.3% of patients

PMID:29705996 · one of two readings recorded this

Efficacy after switch compared with previous FAE mixture

no effect

The data show that the efficacy remained unchanged in the majority of patients

PMID:30644638 · one of two readings recorded this

Tolerability (gastrointestinal complaints, flushing) after switch

no effect

Tolerability (e.g. gastrointestinal complaints and flushing) of the DMF drug was rated equal or better in most patients than with the previous treatment

PMID:30644638 · one of two readings recorded this

CD19+ B lymphocyte count, change from baseline

decreases, p = 0.0001

B lymphocytes (CD19+) | 270.3 ± 202.8 | −18.8 (−30.8, −6.8) | 0.002 | −23.5 (−38.1, −9.0) | 0.002 | −27.7 (−36.5, −18.8) | <0.0001 | −24.5 (−30.1, −18.9) | <0.0001 | −11.5 (−21.4, −1.5) | 0.024

PMID:30680823 · one of two readings recorded this

CD19+ B lymphocyte count, change from baseline

decreases, p = 0.0001

B lymphocytes (CD19+) | 270.3 ± 202.8 | −18.8 (−30.8, −6.8) | 0.002 | −23.5 (−38.1, −9.0) | 0.002 | −27.7 (−36.5, −18.8) | <0.0001 | −24.5 (−30.1, −18.9) | <0.0001 | −11.5 (−21.4, −1.5) | 0.024

PMID:30680823 · one of two readings recorded this

CD19+ B lymphocyte count, change from baseline

decreases, p = 0.002

B lymphocytes (CD19+) | 270.3 ± 202.8 | −18.8 (−30.8, −6.8) | 0.002 | −23.5 (−38.1, −9.0) | 0.002 | −27.7 (−36.5, −18.8) | <0.0001 | −24.5 (−30.1, −18.9) | <0.0001 | −11.5 (−21.4, −1.5) | 0.024

PMID:30680823 · one of two readings recorded this

CD19+ B lymphocyte count, change from baseline

decreases, p = 0.024

B lymphocytes (CD19+) | 270.3 ± 202.8 | −18.8 (−30.8, −6.8) | 0.002 | −23.5 (−38.1, −9.0) | 0.002 | −27.7 (−36.5, −18.8) | <0.0001 | −24.5 (−30.1, −18.9) | <0.0001 | −11.5 (−21.4, −1.5) | 0.024

PMID:30680823 · one of two readings recorded this

CD19+ B lymphocyte count, change from baseline

decreases, p = 0.002

B lymphocytes (CD19+) | 270.3 ± 202.8 | −18.8 (−30.8, −6.8) | 0.002 | −23.5 (−38.1, −9.0) | 0.002 | −27.7 (−36.5, −18.8) | <0.0001 | −24.5 (−30.1, −18.9) | <0.0001 | −11.5 (−21.4, −1.5) | 0.024

PMID:30680823 · one of two readings recorded this

CD3+ T lymphocyte count, change from baseline

decreases, p = 0.0001

T lymphocytes (CD3+) | 1272.8 ± 574.6 | −12.1 (−25.4, 1.1) | 0.073 | −43.0 (−48.4, −37.6) | <0.0001 | −47.8 (−53.2, −42.3) | <0.0001 | −54.5 (−58.5, −50.5) | <0.0001 | −48.3 (−54.2, −42.3) | <0.0001

PMID:30680823 · one of two readings recorded this

CD3+ T lymphocyte count, change from baseline

decreases, p = 0.0001

T lymphocytes (CD3+) | 1272.8 ± 574.6 | −12.1 (−25.4, 1.1) | 0.073 | −43.0 (−48.4, −37.6) | <0.0001 | −47.8 (−53.2, −42.3) | <0.0001 | −54.5 (−58.5, −50.5) | <0.0001 | −48.3 (−54.2, −42.3) | <0.0001

PMID:30680823 · one of two readings recorded this

CD3+ T lymphocyte count, change from baseline

no effect, p = 0.073

T lymphocytes (CD3+) | 1272.8 ± 574.6 | −12.1 (−25.4, 1.1) | 0.073 | −43.0 (−48.4, −37.6) | <0.0001 | −47.8 (−53.2, −42.3) | <0.0001 | −54.5 (−58.5, −50.5) | <0.0001 | −48.3 (−54.2, −42.3) | <0.0001

PMID:30680823 · one of two readings recorded this

CD3+ T lymphocyte count, change from baseline

decreases, p = 0.0001

T lymphocytes (CD3+) | 1272.8 ± 574.6 | −12.1 (−25.4, 1.1) | 0.073 | −43.0 (−48.4, −37.6) | <0.0001 | −47.8 (−53.2, −42.3) | <0.0001 | −54.5 (−58.5, −50.5) | <0.0001 | −48.3 (−54.2, −42.3) | <0.0001

PMID:30680823 · one of two readings recorded this

CD3+ T lymphocyte count, change from baseline

decreases, p = 0.0001

T lymphocytes (CD3+) | 1272.8 ± 574.6 | −12.1 (−25.4, 1.1) | 0.073 | −43.0 (−48.4, −37.6) | <0.0001 | −47.8 (−53.2, −42.3) | <0.0001 | −54.5 (−58.5, −50.5) | <0.0001 | −48.3 (−54.2, −42.3) | <0.0001

PMID:30680823 · one of two readings recorded this

CD4/CD8 ratio, change from baseline

increases, p = 0.0001

CD4/CD8 ratio | 2.2 ± 1.7 | 20.7 (7.4, 33.9) | 0.003 | 31.7 (23.1, 40.4) | <0.0001 | 49.5 (35.7, 63.3) | <0.0001 | 45.2 (31.6, 58.8) | <0.0001 | 34.1 (24.3, 44.0) | <0.0001

PMID:30680823 · one of two readings recorded this

CD4/CD8 ratio, change from baseline

increases, p = 0.0001

CD4/CD8 ratio | 2.2 ± 1.7 | 20.7 (7.4, 33.9) | 0.003 | 31.7 (23.1, 40.4) | <0.0001 | 49.5 (35.7, 63.3) | <0.0001 | 45.2 (31.6, 58.8) | <0.0001 | 34.1 (24.3, 44.0) | <0.0001

PMID:30680823 · one of two readings recorded this

CD4/CD8 ratio, change from baseline

increases, p = 0.003

CD4/CD8 ratio | 2.2 ± 1.7 | 20.7 (7.4, 33.9) | 0.003 | 31.7 (23.1, 40.4) | <0.0001 | 49.5 (35.7, 63.3) | <0.0001 | 45.2 (31.6, 58.8) | <0.0001 | 34.1 (24.3, 44.0) | <0.0001

PMID:30680823 · one of two readings recorded this

CD4/CD8 ratio, change from baseline

increases, p = 0.0001

CD4/CD8 ratio | 2.2 ± 1.7 | 20.7 (7.4, 33.9) | 0.003 | 31.7 (23.1, 40.4) | <0.0001 | 49.5 (35.7, 63.3) | <0.0001 | 45.2 (31.6, 58.8) | <0.0001 | 34.1 (24.3, 44.0) | <0.0001

PMID:30680823 · one of two readings recorded this

CD4/CD8 ratio, change from baseline

increases, p = 0.0001

CD4/CD8 ratio | 2.2 ± 1.7 | 20.7 (7.4, 33.9) | 0.003 | 31.7 (23.1, 40.4) | <0.0001 | 49.5 (35.7, 63.3) | <0.0001 | 45.2 (31.6, 58.8) | <0.0001 | 34.1 (24.3, 44.0) | <0.0001

PMID:30680823 · one of two readings recorded this

CD4+ T helper cell count, change from baseline

decreases, p = 0.0001

T helper cells (CD3+CD4+) | 817.1 ± 364.9 | −16.9 (−25.9, −7.9) | 0.0003 | −41.8 (−46.8, −36.8) | <0.0001 | −47.3 (−51.4, −43.3) | <0.0001 | −49.9 (−54.1, −45.6) | <0.0001 | −46.7 (−52.4, −40.9) | <0.0001

PMID:30680823 · one of two readings recorded this

CD4+ T helper cell count, change from baseline

decreases, p = 0.0001

T helper cells (CD3+CD4+) | 817.1 ± 364.9 | −16.9 (−25.9, −7.9) | 0.0003 | −41.8 (−46.8, −36.8) | <0.0001 | −47.3 (−51.4, −43.3) | <0.0001 | −49.9 (−54.1, −45.6) | <0.0001 | −46.7 (−52.4, −40.9) | <0.0001

PMID:30680823 · one of two readings recorded this

CD4+ T helper cell count, change from baseline

decreases, p = 0.0003

T helper cells (CD3+CD4+) | 817.1 ± 364.9 | −16.9 (−25.9, −7.9) | 0.0003 | −41.8 (−46.8, −36.8) | <0.0001 | −47.3 (−51.4, −43.3) | <0.0001 | −49.9 (−54.1, −45.6) | <0.0001 | −46.7 (−52.4, −40.9) | <0.0001

PMID:30680823 · one of two readings recorded this

CD4+ T helper cell count, change from baseline

decreases, p = 0.0001

T helper cells (CD3+CD4+) | 817.1 ± 364.9 | −16.9 (−25.9, −7.9) | 0.0003 | −41.8 (−46.8, −36.8) | <0.0001 | −47.3 (−51.4, −43.3) | <0.0001 | −49.9 (−54.1, −45.6) | <0.0001 | −46.7 (−52.4, −40.9) | <0.0001

PMID:30680823 · one of two readings recorded this

CD4+ T helper cell count, change from baseline

decreases, p = 0.0001

T helper cells (CD3+CD4+) | 817.1 ± 364.9 | −16.9 (−25.9, −7.9) | 0.0003 | −41.8 (−46.8, −36.8) | <0.0001 | −47.3 (−51.4, −43.3) | <0.0001 | −49.9 (−54.1, −45.6) | <0.0001 | −46.7 (−52.4, −40.9) | <0.0001

PMID:30680823 · one of two readings recorded this

CD56+ NK cell count, change from baseline

decreases, p = 0.0001

NK cells (CD3−CD16+CD56+) | 255.4 ± 154.8 | −3.9 (−11.4, 3.6) | 0.31 | −15.3 (−23.2, −7.5) | 0.0002 | −21.9 (−27.9, −15.9) | <0.0001 | −11.3 (−19.0, −3.5) | 0.004 | 4.5 (−5.8, 14.8) | 0.39

PMID:30680823 · one of two readings recorded this

CD56+ NK cell count, change from baseline

decreases, p = 0.004

NK cells (CD3−CD16+CD56+) | 255.4 ± 154.8 | −3.9 (−11.4, 3.6) | 0.31 | −15.3 (−23.2, −7.5) | 0.0002 | −21.9 (−27.9, −15.9) | <0.0001 | −11.3 (−19.0, −3.5) | 0.004 | 4.5 (−5.8, 14.8) | 0.39

PMID:30680823 · one of two readings recorded this

CD56+ NK cell count, change from baseline

no effect, p = 0.31

NK cells (CD3−CD16+CD56+) | 255.4 ± 154.8 | −3.9 (−11.4, 3.6) | 0.31 | −15.3 (−23.2, −7.5) | 0.0002 | −21.9 (−27.9, −15.9) | <0.0001 | −11.3 (−19.0, −3.5) | 0.004 | 4.5 (−5.8, 14.8) | 0.39

PMID:30680823 · one of two readings recorded this

CD56+ NK cell count, change from baseline

no effect, p = 0.39

NK cells (CD3−CD16+CD56+) | 255.4 ± 154.8 | −3.9 (−11.4, 3.6) | 0.31 | −15.3 (−23.2, −7.5) | 0.0002 | −21.9 (−27.9, −15.9) | <0.0001 | −11.3 (−19.0, −3.5) | 0.004 | 4.5 (−5.8, 14.8) | 0.39

PMID:30680823 · one of two readings recorded this

CD56+ NK cell count, change from baseline

decreases, p = 0.0002

NK cells (CD3−CD16+CD56+) | 255.4 ± 154.8 | −3.9 (−11.4, 3.6) | 0.31 | −15.3 (−23.2, −7.5) | 0.0002 | −21.9 (−27.9, −15.9) | <0.0001 | −11.3 (−19.0, −3.5) | 0.004 | 4.5 (−5.8, 14.8) | 0.39

PMID:30680823 · one of two readings recorded this

CD8+ T cytotoxic cell count, change from baseline

decreases, p = 0.0001

T cytotoxic cells (CD3+CD8+) | 444.9 ± 272.9 | −19.7 (−29.1, −10.2) | <0.0001 | −48.7 (−54.1, −43.4) | <0.0001 | −55.2 (−59.7, −50.8) | <0.0001 | −55.7 (−61.3, −50.1) | <0.0001 | −51.6 (−60.1, −43.1) | <0.0001

PMID:30680823 · one of two readings recorded this

CD8+ T cytotoxic cell count, change from baseline

decreases, p = 0.0001

T cytotoxic cells (CD3+CD8+) | 444.9 ± 272.9 | −19.7 (−29.1, −10.2) | <0.0001 | −48.7 (−54.1, −43.4) | <0.0001 | −55.2 (−59.7, −50.8) | <0.0001 | −55.7 (−61.3, −50.1) | <0.0001 | −51.6 (−60.1, −43.1) | <0.0001

PMID:30680823 · one of two readings recorded this

CD8+ T cytotoxic cell count, change from baseline

decreases, p = 0.0001

T cytotoxic cells (CD3+CD8+) | 444.9 ± 272.9 | −19.7 (−29.1, −10.2) | <0.0001 | −48.7 (−54.1, −43.4) | <0.0001 | −55.2 (−59.7, −50.8) | <0.0001 | −55.7 (−61.3, −50.1) | <0.0001 | −51.6 (−60.1, −43.1) | <0.0001

PMID:30680823 · one of two readings recorded this

CD8+ T cytotoxic cell count, change from baseline

decreases, p = 0.0001

T cytotoxic cells (CD3+CD8+) | 444.9 ± 272.9 | −19.7 (−29.1, −10.2) | <0.0001 | −48.7 (−54.1, −43.4) | <0.0001 | −55.2 (−59.7, −50.8) | <0.0001 | −55.7 (−61.3, −50.1) | <0.0001 | −51.6 (−60.1, −43.1) | <0.0001

PMID:30680823 · one of two readings recorded this

CD8+ T cytotoxic cell count, change from baseline

decreases, p = 0.0001

T cytotoxic cells (CD3+CD8+) | 444.9 ± 272.9 | −19.7 (−29.1, −10.2) | <0.0001 | −48.7 (−54.1, −43.4) | <0.0001 | −55.2 (−59.7, −50.8) | <0.0001 | −55.7 (−61.3, −50.1) | <0.0001 | −51.6 (−60.1, −43.1) | <0.0001

PMID:30680823 · one of two readings recorded this

Hazard of T-cell lymphopenia, age at FAE initiation (per year)

increases

Age at the time of initiating FAE therapy | 1.03 * (1.02, 1.04) | 1.03 * (1.02, 1.04)

PMID:30680823 · one of two readings recorded this

Hazard of T-cell lymphopenia, age at FAE initiation (per year)

increases

Age at the time of initiating FAE therapy | 1.03 * (1.02, 1.04) | 1.03 * (1.02, 1.04)

PMID:30680823 · one of two readings recorded this

Hazard of T-cell lymphopenia, age group 40–55 years

increases

Age group 40–55 years † (reference 29, 30) | 1.62 * (1.12, 2.36)

PMID:30680823 · one of two readings recorded this

Hazard of T-cell lymphopenia, age group >55 years

increases

Age group >55 years † (reference 49) | 2.42 * (1.65, 3.55)

PMID:30680823 · one of two readings recorded this

Hazard of T-cell lymphopenia, FAEs + MTX

decreases

FAEs + MTX | 0.63 (0.38, 1.04) | 0.50 * (0.27, 0.92)

PMID:30680823 · one of two readings recorded this

Hazard of T-cell lymphopenia, FAEs + MTX

no effect

FAEs + MTX | 0.63 (0.38, 1.04) | 0.50 * (0.27, 0.92)

PMID:30680823 · one of two readings recorded this

Hazard of T-cell lymphopenia, FAEs + phototherapy

no effect

FAEs + phototherapy | 1.17 (0.76, 1.78) | 0.97 (0.57, 1.63)

PMID:30680823 · one of two readings recorded this

Hazard of T-cell lymphopenia, FAEs + phototherapy

no effect

FAEs + phototherapy | 1.17 (0.76, 1.78) | 0.97 (0.57, 1.63)

PMID:30680823 · one of two readings recorded this

Hazard of T-cell lymphopenia, female sex

no effect

Female | 1.11 (0.80, 1.53) | 0.86 (0.56, 1.31)

PMID:30680823 · one of two readings recorded this

Hazard of T-cell lymphopenia, female sex

no effect

Female | 1.11 (0.80, 1.53) | 0.86 (0.56, 1.31)

PMID:30680823 · one of two readings recorded this

Leucocyte count, change from baseline

decreases, p = 0.0001

Leucocytes | 7433.5 ± 2339.8 | −9.3 (−13.1, −5.5) | <0.0001 | −16.4 (−20.7, −12.1) | <0.0001 | −20.7 (−24.0, −17.5) | <0.0001 | −18.8 (−22.9, −14.7) | <0.0001 | −17.6 (−24.2, −10.9) | <0.0001

PMID:30680823 · one of two readings recorded this

Leucocyte count, change from baseline

decreases, p = 0.0001

Leucocytes | 7433.5 ± 2339.8 | −9.3 (−13.1, −5.5) | <0.0001 | −16.4 (−20.7, −12.1) | <0.0001 | −20.7 (−24.0, −17.5) | <0.0001 | −18.8 (−22.9, −14.7) | <0.0001 | −17.6 (−24.2, −10.9) | <0.0001

PMID:30680823 · one of two readings recorded this

Leucocyte count, change from baseline

decreases, p = 0.0001

Leucocytes | 7433.5 ± 2339.8 | −9.3 (−13.1, −5.5) | <0.0001 | −16.4 (−20.7, −12.1) | <0.0001 | −20.7 (−24.0, −17.5) | <0.0001 | −18.8 (−22.9, −14.7) | <0.0001 | −17.6 (−24.2, −10.9) | <0.0001

PMID:30680823 · one of two readings recorded this

Leucocyte count, change from baseline

decreases, p = 0.0001

Leucocytes | 7433.5 ± 2339.8 | −9.3 (−13.1, −5.5) | <0.0001 | −16.4 (−20.7, −12.1) | <0.0001 | −20.7 (−24.0, −17.5) | <0.0001 | −18.8 (−22.9, −14.7) | <0.0001 | −17.6 (−24.2, −10.9) | <0.0001

PMID:30680823 · one of two readings recorded this

Leucocyte count, change from baseline

decreases, p = 0.0001

Leucocytes | 7433.5 ± 2339.8 | −9.3 (−13.1, −5.5) | <0.0001 | −16.4 (−20.7, −12.1) | <0.0001 | −20.7 (−24.0, −17.5) | <0.0001 | −18.8 (−22.9, −14.7) | <0.0001 | −17.6 (−24.2, −10.9) | <0.0001

PMID:30680823 · one of two readings recorded this

Lymphocyte count, change from baseline

decreases, p = 0.0001

Lymphocytes | 1962.0 ± 679.9 | −23.9 (−28.9, −19.0) | <0.0001 | −39.3 (−45.1, −33.4) | <0.0001 | −44.1 (−48.2, −40.0) | <0.0001 | −39.4 (−46.8, −31.9) | <0.0001 | −45.1 (−51.5, −38.7) | <0.0001

PMID:30680823 · one of two readings recorded this

Lymphocyte count, change from baseline

decreases, p = 0.0001

Lymphocytes | 1962.0 ± 679.9 | −23.9 (−28.9, −19.0) | <0.0001 | −39.3 (−45.1, −33.4) | <0.0001 | −44.1 (−48.2, −40.0) | <0.0001 | −39.4 (−46.8, −31.9) | <0.0001 | −45.1 (−51.5, −38.7) | <0.0001

PMID:30680823 · one of two readings recorded this

Lymphocyte count, change from baseline

decreases, p = 0.0001

Lymphocytes | 1962.0 ± 679.9 | −23.9 (−28.9, −19.0) | <0.0001 | −39.3 (−45.1, −33.4) | <0.0001 | −44.1 (−48.2, −40.0) | <0.0001 | −39.4 (−46.8, −31.9) | <0.0001 | −45.1 (−51.5, −38.7) | <0.0001

PMID:30680823 · one of two readings recorded this

Lymphocyte count, change from baseline

decreases, p = 0.0001

Lymphocytes | 1962.0 ± 679.9 | −23.9 (−28.9, −19.0) | <0.0001 | −39.3 (−45.1, −33.4) | <0.0001 | −44.1 (−48.2, −40.0) | <0.0001 | −39.4 (−46.8, −31.9) | <0.0001 | −45.1 (−51.5, −38.7) | <0.0001

PMID:30680823 · one of two readings recorded this

Lymphocyte count, change from baseline

decreases, p = 0.0001

Lymphocytes | 1962.0 ± 679.9 | −23.9 (−28.9, −19.0) | <0.0001 | −39.3 (−45.1, −33.4) | <0.0001 | −44.1 (−48.2, −40.0) | <0.0001 | −39.4 (−46.8, −31.9) | <0.0001 | −45.1 (−51.5, −38.7) | <0.0001

PMID:30680823 · one of two readings recorded this

PASI 75 response, log-rank comparison among three groups

no effect, p = 0.43

The PASI 75 results were not significantly different among the three groups (P = 0.43)

PMID:30680823 · one of two readings recorded this

Patients developing lymphopenia during FAE therapy

increases

In the subcohort, 60.9% of the psoriasis patients developed lymphopenia

PMID:30680823 · one of two readings recorded this

Patients developing severe lymphopenia (CTCAE grade 3 or 4)

increases

Severe lymphopenia (CTCAE grade 3 or 4) occurred in 14.3% of the patients

PMID:30680823 · one of two readings recorded this

sPGA response, log-rank comparison among three groups

no effect, p = 0.07

The sPGA results were not significantly different among the three groups (P = 0.07)

PMID:30680823 · one of two readings recorded this

Time to cumulative PASI 75 response rate of 50%, group with CD4+ <200/μL and CD8+ <140/μL

was 3 years (95% CI: 2–4 years) compared with 3.8 years (95% CI: 3–6.3 years)

PMID:30680823 · one of two readings recorded this

Time to cumulative PASI 75 response rate of 50%, group with CD4+ >=200/μL and CD8+ >=140/μL

was 3 years (95% CI: 2–4 years) compared with 3.8 years (95% CI: 3–6.3 years)

PMID:30680823 · one of two readings recorded this

Time to cumulative PASI 75 response rate of 50%, group with CD4+ <200/μL or CD8+ <140/μL

and 3.9 years (95% CI: 3–6.7 years)

PMID:30680823 · one of two readings recorded this

Time to cumulative sPGA response rate of 50%, group with CD4+ >=200/μL and CD8+ >=140/μL

no effect

was 0.49 years (95% CI: 0.49–0.99 years) compared with 0.99 years (95% CI: 0.49–0.99 years)

PMID:30680823 · one of two readings recorded this

Time to cumulative sPGA response rate of 50%, group with CD4+ <200/μL and/or CD8+ <140/μL

no effect

was 0.49 years (95% CI: 0.49–0.99 years) compared with 0.99 years (95% CI: 0.49–0.99 years)

PMID:30680823 · one of two readings recorded this

PASI 100 response

increases, p = 0.001

PASI 100 [41% vs. 4% FAEs (P < 0·001) and 13% methotrexate (P = 0·0041)]

PMID:31376153 · one of two readings recorded this

PASI 100 response

increases, p = 0.0041

PASI 100 [41% vs. 4% FAEs (P < 0·001) and 13% methotrexate (P = 0·0041)]

PMID:31376153 · one of two readings recorded this

PASI 75 response

increases, p = 0.001

PASI 75 [91% vs. 22% FAEs (P < 0·001) and 70% methotrexate (P = 0·014)]

PMID:31376153 · one of two readings recorded this

PASI 75 response

increases, p = 0.014

PASI 75 [91% vs. 22% FAEs (P < 0·001) and 70% methotrexate (P = 0·014)]

PMID:31376153 · one of two readings recorded this

PASI 90 response

increases, p = 0.001

PASI 90 [80% vs. 9% FAEs (P < 0·001) and 39% methotrexate (P < 0·001)]

PMID:31376153 · one of two readings recorded this

PASI 90 response

increases, p = 0.001

PASI 90 [80% vs. 9% FAEs (P < 0·001) and 39% methotrexate (P < 0·001)]

PMID:31376153 · one of two readings recorded this

Average drug survival

Ten percent of all patients had FAE-treatment for 10 years or longer with an average drug survival of 4.32 years

PMID:31682772 · one of two readings recorded this

PASI 75 response during long-term treatment

The PASI 75 response was achieved in 44% of the patient during long-term treatment without remarkable differences between moderate or severe plaque psoriasis

PMID:31682772 · one of two readings recorded this

PASI 75 response proportion in psoriasis patients on fumaric acid ester therapy, retrospective single-arm

44% achieved PASI 75

Not recorded as a finding: this platform holds no node for the endpoint

The PASI 75 response was achieved in 44% of the patient during long-term treatment without remarkable differences between moderate or severe plaque psoriasis.

PMID:31682772 · one of two readings recorded this

PASI 75 response proportion in psoriasis patients on fumaric acid esters

44% achieved PASI 75

Not recorded as a finding: a node exists but the paper states a different instrument or population

The PASI 75 response was achieved in 44% of the patient during long-term treatment without remarkable differences between moderate or severe plaque psoriasis.

PMID:31682772 · one of two readings recorded this

Patients who stopped therapy during the first six months

In our population, 14% of the patients stopped therapy during the first six month mainly due to gastro-intestinal side effects

PMID:31682772 · one of two readings recorded this

Responders with improvement of psoriasis to clear

Seventy-eight percent of the patients responded to FAE therapy with improvement of their psoriasis to mild (61%) or clear (17%)

PMID:31682772 · one of two readings recorded this

Responders with improvement of psoriasis to mild

Seventy-eight percent of the patients responded to FAE therapy with improvement of their psoriasis to mild (61%) or clear (17%)

PMID:31682772 · one of two readings recorded this

beta-alanine titer from fumaric acid

2250 mM (200.3 g/L) β-Ala was obtained from fumaric acid with a conversion rate of 90.0%

PMID:32524454 · one of two readings recorded this

beta-alanine titer from L-aspartic acid

3050 mM (271.5 g/L) β-Ala was achieved from L-aspartic acid by using the whole-cell biocatalyst co-expressing BSADC and TCADC, corresponding to a conversion rate of 92.4%

PMID:32524454 · one of two readings recorded this

conversion rate to beta-alanine from fumaric acid

2250 mM (200.3 g/L) β-Ala was obtained from fumaric acid with a conversion rate of 90.0%

PMID:32524454 · one of two readings recorded this

conversion rate to beta-alanine from L-aspartic acid

3050 mM (271.5 g/L) β-Ala was achieved from L-aspartic acid by using the whole-cell biocatalyst co-expressing BSADC and TCADC, corresponding to a conversion rate of 92.4%

PMID:32524454 · one of two readings recorded this

anti-inflammatory effect of topical LOX gel

increases

The topical LOX gel using fumaric acid as penetration enhancer had higher transdermal rate, significant anti-inflammatory effect and no obvious skin irritation

PMID:32805639 · one of two readings recorded this

loxoprofen sodium distribution in stratum corneum

increases

The preliminary mechanism investigation inferred that fumaric acid could increase LOX's distribution in stratum corneum and might change its complexation state, but had little effect on the drug structure and skin's lipids and proteins configuration

PMID:32805639 · one of two readings recorded this

penetration rate of loxoprofen sodium

increases

The results showed that lactic acid and fumaric acid could significantly increase the penetration rate of LOX and reduce time lag even without the help of acidic environment

PMID:32805639 · one of two readings recorded this

penetration time lag of loxoprofen sodium

decreases

The results showed that lactic acid and fumaric acid could significantly increase the penetration rate of LOX and reduce time lag even without the help of acidic environment

PMID:32805639 · one of two readings recorded this

skin irritation of topical LOX gel

no effect

The topical LOX gel using fumaric acid as penetration enhancer had higher transdermal rate, significant anti-inflammatory effect and no obvious skin irritation

PMID:32805639 · one of two readings recorded this

skin lipid and protein configuration

no effect

The preliminary mechanism investigation inferred that fumaric acid could increase LOX's distribution in stratum corneum and might change its complexation state, but had little effect on the drug structure and skin's lipids and proteins configuration

PMID:32805639 · one of two readings recorded this

transdermal penetration rate and lag time of loxoprofen sodium through skin in vitro with fumaric acid as penetration enhancer

increases, significantly increased penetration rate and reduced time lag

Not recorded as a finding: this platform holds no node for the endpoint

The results showed that lactic acid and fumaric acid could significantly increase the penetration rate of LOX and reduce time lag even without the help of acidic environment.

PMID:32805639 · one of two readings recorded this

transdermal rate of topical LOX gel

increases

The topical LOX gel using fumaric acid as penetration enhancer had higher transdermal rate, significant anti-inflammatory effect and no obvious skin irritation

PMID:32805639 · one of two readings recorded this

Dermatology Life Quality Index

decreases, p = 0.001

DLQI scores were significantly lower (reflecting better health-related quality of life) with risankizumab vs. FAEs, with least squares (LS) mean differences of -7.4 and -7.6 at weeks 16 and 24, respectively (both P < 0.001)

PMID:33428281 · one of two readings recorded this

Dermatology Life Quality Index

decreases, p = 0.001

DLQI scores were significantly lower (reflecting better health-related quality of life) with risankizumab vs. FAEs, with least squares (LS) mean differences of -7.4 and -7.6 at weeks 16 and 24, respectively (both P < 0.001)

PMID:33428281 · one of two readings recorded this

Patient Benefit Index

increases, p = 0.001

PBI was significantly higher, indicating greater benefit, with risankizumab vs. FAEs, with an LS mean difference of 1.1 and 1.3 at weeks 16 and 24, respectively (both P < 0.001)

PMID:33428281 · one of two readings recorded this

Patient Benefit Index

increases, p = 0.001

PBI was significantly higher, indicating greater benefit, with risankizumab vs. FAEs, with an LS mean difference of 1.1 and 1.3 at weeks 16 and 24, respectively (both P < 0.001)

PMID:33428281 · one of two readings recorded this

Psoriasis Symptom Scale total and redness, itching, burning scores

decreases, p = 0.001

A significant PSS improvement was observed with risankizumab vs. FAEs at weeks 16 and 24 for total and psoriasis-associated redness, itching and burning scores (P < 0.001)

PMID:33428281 · one of two readings recorded this

Psoriasis Symptom Scale total and redness, itching, burning scores

decreases, p = 0.001

A significant PSS improvement was observed with risankizumab vs. FAEs at weeks 16 and 24 for total and psoriasis-associated redness, itching and burning scores (P < 0.001)

PMID:33428281 · one of two readings recorded this

SF-36 PCS and MCS, HADS anxiety and depression, PtGA, EQ-5D-5L index and VAS

increases, p = 0.002

Patients randomized to risankizumab also had larger improvements in SF-36 Physical and Mental Component Summary scores, HADS anxiety and depression scores, PtGA, and EQ-5D-5L index and visual analogue scale scores (all P ≤ 0.002) at weeks 16 and 24 compared with FAEs

PMID:33428281 · one of two readings recorded this

Key efficacy endpoints overall

increases, p = 0.001, n = 120

Key efficacy endpoints were met at week 24 for risankizumab (n = 60) vs. FAEs (n = 60) (P < 0·001)

PMID:33991341 · one of two readings recorded this

PASI 100 response

increases, n = 120

≥ 100% improvement in PASI (50·0% vs. 5·0%)

PMID:33991341 · one of two readings recorded this

PASI 50 response

increases, n = 120

≥ 50% improvement in PASI (100% vs. 53·3%)

PMID:33991341 · one of two readings recorded this

PASI 75 response

increases, n = 120

≥ 75% improvement in PASI (98·3% vs. 33·3%)

PMID:33991341 · one of two readings recorded this

PASI 90 response

increases, n = 120

achievement of a ≥ 90% improvement in Psoriasis Area and Severity Index (PASI; primary endpoint 83·3% vs. 10·0%)

PMID:33991341 · one of two readings recorded this

Static Physician's Global Assessment clear/almost clear

increases, n = 120

a Static Physician's Global Assessment of clear/almost clear (93·3% vs. 38·3%)

PMID:33991341 · one of two readings recorded this

inflammatory NF-κB transcription factor activity and NLRP3 inflammasome-associated gene expression in murine and human macrophages

decreases

Not recorded as a finding: the trial gave a chemically different species

The DXM-MMF conjugate displayed improved inhibition of inflammation over the unconjugated combination in both murine and human macrophages.

PMID:34165285 · one of two readings recorded this

NF-κB luciferase reporter activity, DXM+FAE combination

decreases, IC50 reduced up to 4000-fold for DXM and 15-fold for DMF when combined

With the use of NF‐κB luciferase reporter murine macrophages, it was observed that the IC50 was reduced up to 4000‐fold for DXM and 15‐fold for DMF when the two agents were combined in various ratios.

PMID:34165285 · one of two readings recorded this

NF-κB transcriptional activity and nitric oxide production inhibition in LPS-activated macrophages (luciferase reporter / Griess-type assay)

decreases, IC50 for NF-κB inhibition reduced up to 4000-fold for DXM and 15-fold for DMF when combined

Not recorded as a finding: the intervention held more than the compound

With the use of NF‐κB luciferase reporter murine macrophages, it was observed that the IC50 was reduced up to 4000‐fold for DXM and 15‐fold for DMF when the two agents were combined in various ratios.

PMID:34165285 · one of two readings recorded this

NF-kB transcription factor activity and NLRP3 inflammasome-associated gene expression in murine and human macrophages

decreases

Not recorded as a finding: the trial gave a chemically different species

Furthermore, this combination was found to synergistically inhibit inflammatory nuclear factor κB (NF-κB) transcription factor activity.

PMID:34165285 · one of two readings recorded this

Effect of food intake on Cmax, Tmax and AUC

no effect

Food intake reduced Cmax and delayed Tmax of ensitrelvir but did not impact the area under the curve (AUC)

PMID:36094202 · one of two readings recorded this

Midazolam AUC with coadministered ensitrelvir 750/250 mg on day 6

increases

Ensitrelvir affected the pharmacokinetics of CYP3A substrates because of increase in AUC of midazolam coadministered with ensitrelvir 750/250 mg on day 6

PMID:36094202 · one of two readings recorded this

Plasma exposure, white versus Japanese participants

decreases

Compared with Japanese participants, plasma exposures were slightly lower for white participants

PMID:36094202 · one of two readings recorded this

extracellular fumaric acid production from malic acid by engineered Saccharomyces cerevisiae strains, HPLC quantification

increases, ΔFUM1(ss) Ckr_fum + mae1 produced 2.01 g/L fumaric acid at 48 h versus 1.49 g/L without the transporter

Not recorded as a finding: the compound is what was measured, not what was given

In the 3:1 medium, strain ΔFUM1(ss) Ckr_fum + mae1 produced 2.01 g/L fumaric acid after 48 h, which was significantly higher than its counterpart without Spmae1 (1.49 g/L), although the two strains achieved similar levels at T72.

PMID:36646426 · one of two readings recorded this

fumaric acid production from extracellular malic acid (g/L)

increases, up to 2.01 g/L at 48h in the best-performing ΔFUM1(ss) Ckr_fum + mae1 strain

In the 3:1 medium, strain ΔFUM1(ss) Ckr_fum + mae1 produced 2.01 g/L fumaric acid after 48 h, which was significantly higher than its counterpart without Spmae1 (1.49 g/L), although the two strains achieved similar levels at T72.

PMID:36646426 · one of two readings recorded this

malic acid utilization (%)

increases, up to 26.6% malic acid utilized at 72h in ΔFUM1Ckr_fum + mae1 under aerobic conditions

Under aerobic conditions, strain ΔFUM1Ckr_fum + mae1 was the best performer, with 26.6% of the extracellular malic acid utilized at T72.

PMID:36646426 · one of two readings recorded this

Effect of food on Cmax and AUC

no effect

although time to Cmax in the fed state was delayed, there was no clinically meaningful difference in the exposure levels (Cmax and AUC) of ensitrelvir between the fasted and fed states

PMID:37798608 · one of two readings recorded this

Plasma concentration at 24 h (C24) after initial 375/125 mg dose versus target plasma concentration

unclear

The plasma concentration at 24 h (C24) after an initial dose of 375/125 mg exceeded the target plasma concentration (6.09 µg/mL) in all populations

PMID:37798608 · one of two readings recorded this

DLQI score of 0/1

72%, 29% and 45%, respectively, achieved a Dermatology Life Quality Index score of 0/1

PMID:38133615 · one of two readings recorded this

maintained PASI score <= 5 after withdrawal

At week 100, 44 weeks postwithdrawal, 47% (n = 17/36) and 25% (n = 3/12) of GUS-GUSw and FAE-GUSw patients, respectively, maintained a PASI score ≤ 5

PMID:38133615 · one of two readings recorded this

maintained PASI score <= 5 after withdrawal

At week 100, 44 weeks postwithdrawal, 47% (n = 17/36) and 25% (n = 3/12) of GUS-GUSw and FAE-GUSw patients, respectively, maintained a PASI score ≤ 5

PMID:38133615 · one of two readings recorded this

PASI 75 responders

At week 32, 98% (n = 54/55) of GUS- and 41% (n = 14/34) of FAE-treated patients were PASI 75 responders

PMID:38133615 · one of two readings recorded this

PASI 75 responders

At week 32, 98% (n = 54/55) of GUS- and 41% (n = 14/34) of FAE-treated patients were PASI 75 responders

PMID:38133615 · one of two readings recorded this

PASI 90 response

At week 56, 91%, 50% and 80% of GUSr-GUS, FAEr-FAE and FAEnr-GUS patients, respectively, achieved a PASI 90 response

PMID:38133615 · one of two readings recorded this

discontinuation due to inadequate treatment response, by depression status

no effect, no significant effect of depression or sex

There was neither a significant effect of “depression” (z = 0.13, n.s,) or sex (z = –1.32, n.s.), nor a significant interaction effect of the two factors (z = 0.25, n.s.).

PMID:38483082 · one of two readings recorded this

overall treatment discontinuation within 52 weeks

60/95 (63.16%) discontinued within 52 weeks; most common reason was adverse events (70.00%), n = 95

N = 60 (63.16%) patients discontinued treatment within the first 52 weeks after initiation.

PMID:38483082 · one of two readings recorded this

therapy discontinuation due to adverse events or inadequate response among psoriasis patients on FAE therapy, stratified by depressive symptomatology

increases, n = 95

Not recorded as a finding: the trial gave a chemically different species

Psoriasis patients (N = 95, 47.37% female) with depressive symptomatology (42.11%) were more likely to discontinue therapy due to patient-reported AEs, while the total number of reported AEs was not associated with depression.

PMID:38483082 · one of two readings recorded this

fumaric acid production titre (g/L)

increases, 5.65 g/L (R. circicans 1475) and 5.25 g/L (Rhizopus sp. 3271) at 30°C, 120 rpm, 96 h

Rhizopus circicans 1475 and Rhizopus 3271 achieved productions of 5.65 g.L-1 and 5.25 g.L-1 of fumaric acid at 30 °C, 120 rpm for 96 h, respectively.

PMID:38671219 · one of two readings recorded this

fumaric acid production yield from Rhizopus fermentation of oil palm empty fruit bunch hydrolysate (g/L)

increases, 5.65 g/L and 5.25 g/L fumaric acid produced by R. circicans 1475 and Rhizopus sp. 3271 respectively

Not recorded as a finding: the compound is what was measured, not what was given

Rhizopus circicans 1475 and Rhizopus 3271 achieved productions of 5.65 g.L-1 and 5.25 g.L-1 of fumaric acid at 30 °C, 120 rpm for 96 h, respectively.

PMID:38671219 · one of two readings recorded this

glutathione depletion

decreases, only DMF and DEF caused significant depletion

Only DMF and DEF caused statistically significant glutathione depletion in exposed cells.

PMID:38794848 · one of two readings recorded this

NRF2 stabilization and FOXO-dependent target gene activation in cultured human hepatoma cells

increases

Not recorded as a finding: the trial gave a chemically different species

Whereas only the diesters caused acute glutathione depletion and activation of the stress kinase p38MAPK, all four FAEs stimulated NRF2 stabilization and upregulation of NRF2 target genes.

PMID:38794848 · one of two readings recorded this

NRF2 stabilization and upregulation of NRF2 target genes in cultured human hepatoma cells

increases

Not recorded as a finding: the trial gave a chemically different species

all four FAEs stimulated NRF2 stabilization and upregulation of NRF2 target genes.

PMID:38794848 · one of two readings recorded this

NRF2 target gene expression (HMOX1, GCLC, NQO1, G6PD)

increases, HMOX1 most sensitive, induced by DEF and DMF by 4h

Of the tested target genes, HMOX1 appeared to be the most sensitive toward exposure to FAEs, with highly significant induction observed upon exposure to DEF (like DEM) and DMF already after 4 h.

PMID:38794848 · one of two readings recorded this

NRF2 target gene mRNA induction (HMOX1, GCLC, NQO1, G6PD) in HepG2 cells exposed to FAEs

increases, HMOX1 mRNA was the most sensitive target, significantly induced by DEF and DMF by 4 h

Not recorded as a finding: gene-expression readout of the same Nrf2 pathway already captured at the protein level (glutathione depletion, p38MAPK activation extracted as mechanism claims); recorded here rather than as a separate mechanism claim to avoid duplicating the pathway finding

Of the tested target genes, HMOX1 appeared to be the most sensitive toward exposure to FAEs, with highly significant induction observed upon exposure to DEF (like DEM) and DMF already after 4 h.

PMID:38794848 · one of two readings recorded this

p38MAPK phosphorylation

increases, only DMF and DEF elicited significant phosphorylation

This FAE reactivity pattern is also reflected at a cellular signaling level: only DMF and DEF elicited statistically significant phosphorylation (activation) of the kinase p38MAPK, which is known to respond to a variety of stress‐inducing stimuli.

PMID:38794848 · one of two readings recorded this

depressive-like behavior in ciprofloxacin-treated rats, assessed by unnamed 'behavior tests'

decreases

Not recorded as a finding: this platform holds no node for the endpoint

Fumaric acid has beneficial effects as an anti-depressant in Wistar albino male rats that received ciprofloxacin.

PMID:39563658 · one of two readings recorded this

cascade rate-limiting step

decarboxylation of aspartic acid was rate-limiting; EcMAL activity ~8x that of CgPanD

The enzyme kinetic parameters and enzyme activity of EcMAL and CgPanD showed that the rate-limiting step in the cascade was the decarboxylation of aspartic acid.

PMID:39766260 · one of two readings recorded this

cascade reaction rate-limiting step, comparing EcMAL and CgPanD enzyme activities

the rate-limiting step in the cascade was the decarboxylation of aspartic acid; EcMAL activity was about eight times that of CgPanD

Not recorded as a finding: characterises downstream cascade kinetics between two enzymes rather than a fumarate-directed mechanism finding beyond the substrate/conversion claims already extracted

The enzyme kinetic parameters and enzyme activity of EcMAL and CgPanD showed that the rate-limiting step in the cascade was the decarboxylation of aspartic acid.

PMID:39766260 · one of two readings recorded this

H2O2-, cisplatin- and erastin-induced renal tubular epithelial cell (HK2) injury — apoptosis and ferroptosis pathway activation

decreases, GAA and FA together alleviated H2O2-, cisplatin- and erastin-induced injury by inhibiting apoptosis and ferroptosis

Not recorded as a finding: the intervention held more than the compound

Cellular experiments confirmed that GAA and FA alleviated H2O2-, CDDP- and erastin-induced renal tubular epithelial cell injury by inhibiting apoptosis and ferroptosis.

PMID:40090045 · one of two readings recorded this

H2O2-, cisplatin- and erastin-induced renal tubular epithelial (HK2) cell injury via apoptosis and ferroptosis pathways

decreases

Not recorded as a finding: the intervention held more than the compound

Cellular experiments confirmed that GAA and FA alleviated H2O2-, CDDP- and erastin-induced renal tubular epithelial cell injury by inhibiting apoptosis and ferroptosis.

PMID:40090045 · one of two readings recorded this

renal tubular epithelial cell (HK2) injury induced by H2O2, cisplatin or erastin — apoptosis and ferroptosis

decreases, GAA and FA together alleviated H2O2-, CDDP- and erastin-induced injury by inhibiting apoptosis and ferroptosis

Cellular experiments confirmed that GAA and FA alleviated H2O2-, CDDP- and erastin-induced renal tubular epithelial cell injury by inhibiting apoptosis and ferroptosis.

PMID:40090045 · one of two readings recorded this

renal tubular epithelial (HK2) cell injury -- apoptosis and ferroptosis induced by H2O2, cisplatin (CDDP) and erastin

decreases

Not recorded as a finding: this platform holds no node for the endpoint

Cellular experiments confirmed that GAA and FA alleviated H2O2-, CDDP- and erastin-induced renal tubular epithelial cell injury by inhibiting apoptosis and ferroptosis.

PMID:40090045 · one of two readings recorded this