I recently read that regular use of both paracetamol and ibuprofen can raise your blood pressure.

I had no idea of this before now and it’s not something the doc told me, different sources vary as to the extent - some say a slight rise and others that it can be significant - so it’s something to bear in mind.

I am on a bio but although my skin is doing well it’s hard to tell how well it’s working for my psa. I use painkillers on the advice of my rheumy for when I get stiff neck and shoulders and I can feel it bringing on a headache, or for my Achilles when it’s playing up.

I was wondering if anyone else knew more?

JNJ-2113 is an oral IL-23R antagonist peptide that binds to the IL-23 receptor with single-digit picomolar affinity and demonstrated potent, selective inhibition of IL-23 signaling in human T cell.

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Johnson & Johnson today announced positive topline results from its Phase 2b FRONTIER 1 clinical trial evaluating the novel, first and only oral interleukin-23 receptor (IL-23R) antagonist peptide JNJ-2113 in adult patients with moderate-to-severe plaque psoriasis (PsO). The trial achieved all primary and secondary efficacy endpoints. A greater proportion of patients who received JNJ-2113 achieved PASI 75 (primary endpoint) as well as PASI 90 and PASI 100 (75, 90 and 100 percent improvement in skin lesions as measured by the Psoriasis Area and Severity Index, respectively)a compared to placebo, at week 16. Trial results for JNJ-2113 demonstrated a profile that supports its advancement into Phase 3 clinical development for moderate-to-severe plaque PsO in adult patients.

JNJ-2113 is a novel oral IL-23R antagonist peptide that binds with high affinity to the IL-23R and has properties that allow it to be absorbed with oral dosing. The IL-23/IL-23R signaling pathway plays a critical role in the pathogenesis of immune-mediated inflammatory diseases, including PsO. JNJ-2113 selectively and potently blocks IL-23 signaling and downstream inflammatory cytokine production.

PASI 75 Results – Primary Endpoint

The proportions of adult patients receiving JNJ-2113 (n=212)1 who achieved PASI 75 demonstrated the following dose responses at week 16 compared to 9.3 percent of patients receiving placebo (n=43) (nominal p ≤0.002 for all comparisons):

    37.2 percent at 25 mg daily (n=43)
    51.2 percent at 25 mg twice daily (n=41)
    58.1 percent at 50 mg daily (n=43)
    65.1 percent at 100 mg daily (n=43)
    78.6 percent at 100 mg twice daily (n=42)

PASI 90 Results – Secondary Endpoint

The proportions of adult patients receiving JNJ-2113 who achieved PASI 90 demonstrated the following dose responses at week 16 compared to 2.3 percent of patients receiving placebo (n=43) (nominal p ≤0.002 for all comparisons):

    25.6 percent at 25 mg daily (n=43)
    26.8 percent at 25 mg twice daily (n=41)
    51.2 percent at 50 mg daily (n=43)
    46.5 percent at 100 mg daily (n=43)
    59.5 percent at 100 mg twice daily (n=42)

PASI 100 Results – Secondary Endpoint

The proportions of adult patients receiving JNJ-2113 who achieved PASI 100 also demonstrated the following dose responses at week 16 compared to 0 percent of patients receiving placebo (n=43) (nominal p ≤0.05 for all comparisons):

    11.6 percent at 25 mg daily (n=43)
    9.8 percent at 25 mg twice daily (n=41)
    25.6 percent at 50 mg daily (n=43)
    23.3 percent at 100 mg daily (n=43)
    40.5 percent at 100 mg twice daily (n=42)

Treatment was generally well tolerated, and the proportions of patients with adverse events were comparable between patient groups. The proportion of participants experiencing one or more adverse events (AEs) was 52.4 percent (n=111) in the combined JNJ-2113 group and 51.2 percent (n=22) in the placebo group. Although there was variability across the treatment groups, there was no evidence of a dose-dependent increase in the occurrence of specific AEs across the JNJ-2113 treatment groups. The most frequent system organ class involved in AEs in all groups was infections and infestations, which were 30.2 percent (n=64) vs. 27.9 percent (n=12) in the combined JNJ-2113 group vs. placebo group, respectively; of these, the most common were comparable between groups: COVID-19 (10.8 percent [n=23] vs. 11.6 percent [n=5]), nasopharyngitis (7.1 percent [n=15] vs. 4.7 percent [n=2]) and upper respiratory tract infection (2.4 percent [n=5] vs. 2.3 percent [n=1]).

“The development of a novel oral therapy that specifically targets IL-23R could potentially change the treatment paradigm for patients living with moderate-to-severe plaque psoriasis,” said Lloyd Miller, M.D., Ph.D., Vice President, Immunodermatology Disease Area Stronghold Leader, Janssen Research & Development, LLC. “Until now, advanced psoriasis treatments have been largely limited to injectable biologics. An oral therapy that can uniquely inhibit the IL-23 pathway by directly targeting the IL-23 receptor could help address the needs and preferences of patients, and may offer greater freedom, with the aim of driving greater adoption of advanced treatment.”

Sotyktu (deucravacitinib) is an oral prescription medicine approved by some countries to treat moderate to severe plaque psoriasis in adults.

Dosage: The recommended dose is one 6 mg once daily with or without food. Do not split, break, crush, or chew the tablet.

Tell your doctor if you have or ever had:

• liver or kidney disease;
  
• hepatitis B or C;
  
• high blood levels of fat (triglycerides);
  
• any type of cancer;
  
• tuberculosis or have been exposed to tuberculosis;
  
• if you have an infection that keeps returning or does not go away;
  
• if you are being treated for an infection;
  
• if you have recently received or are scheduled to receive a vaccine;
  
• if you have high blood pressure, high cholesterol, diabetes, menopause, family history of coronary artery disease, being overweight, or being over 50, or if you smoke;
  
• if you are pregnant or breastfeeding.
  

• Prescription medicines
  
• Over-the-counter medicines
  
• Vitamins
  
• Herbal supplements
  

• Feeling faint
  
• Swelling of your face, eyelids, lips, mouth, tongue, or throat
  
• Trouble breathing or throat tightness
  
• Chest tightness
  
• Skin rash, hives
  

• Fever, sweats, or chills
  
• Muscle aches
  
• Weight loss
  
• Cough
  
• Shortness of breath
  
• Blood in your phlegm (mucus you cough up)
  
• Warm, red, or painful skin or sores on your body different from your psoriasis
  
• Diarrhoea or stomach pain
  
• Burning when you urinate or urinating more often than normal
  
• Feeling very tired
  

The National Institute for Health and Care Excellence (NICE) has recommended Sotyktu (deucravacitinib), for use on the NHS in England for treating moderate to severe plaque psoriasis.

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1 Recommendations:

1.1 Deucravacitinib is recommended as an option for treating moderate to severe plaque psoriasis in adults, only if:

• the Psoriasis Area and Severity Index (PASI) score is 10 or more and the Dermatology Life Quality Index (DLQI) score is more than 10
  
• the condition has not responded to other systemic treatments, including ciclosporin, methotrexate and phototherapy, or these options are contraindicated or not tolerated
  
• the company provides deucravacitinib according to the commercial arrangement.
  

1.2 Consider stopping deucravacitinib between 16 weeks and 24 weeks if there has not been at least a 50% reduction in the PASI score (PASI 50) from when treatment started.

1.3 Consider stopping deucravacitinib at 24 weeks if the psoriasis has not responded adequately. An adequate response is defined as:

• a 75% reduction in the PASI score (PASI 75) from when treatment started or
  
• a 50% reduction in the PASI score (PASI 50) and a 5-point reduction in DLQI from when treatment started.
  

1.4 If people with the condition and their clinicians consider deucravacitinib to be 1 of a range of suitable treatments fter discussing the advantages and disadvantages of all the options, use the least expensive. Take account of administration costs, dosage, price per dose and commercial arrangements.

1.5 Take into account how skin colour could affect the PASI score and make any adjustments needed.

1.6 Take into account any physical, sensory or learning disabilities, or communication difficulties that could affect the responses to the DLQI and make any adjustments needed.

1.7 These recommendations are not intended to affect treatment with deucravacitinib that was started in the NHS before this guidance was published. People having treatment outside these recommendations may continue without change to the funding arrangements in place for them before this guidance was published, until they and their NHS clinician consider it appropriate to stop.

Why the committee made these recommendations:

Treatment for moderate to severe plaque psoriasis that has not responded to conventional systemic non-biological treatments or phototherapy includes apremilast, dimethyl fumarate and systemic biological treatments. Deucravacitinib is an alternative to apremilast, dimethyl fumarate and systemic biological treatments.

Clinical trial evidence shows that deucravacitinib improves symptoms of plaque psoriasis compared with placebo and apremilast. Deucravacitinib was indirectly compared with apremilast, dimethyl fumarate and several systemic biological treatments. The indirect comparison suggests it improves symptoms better than apremilast and dimethyl fumarate, and works as well as some biological treatments but not as well as others.
The cost-effectiveness estimates for deucravacitinib compared with apremilast, dimethyl fumarate and most biological treatments are within the range that NICE normally considers an acceptable use of NHS resources. So, deucravacitinib is recommended.

Around the late fall of 2022, I came to understand a family relationship differently and was able to set down what had been a long-standing burden in my way of viewing life.  That resolution brought me unexpected peace and also unexpected improvement in my patches of rashy areas.  My skin began to heal a bit, improve a bit on its own.

And it has stayed pretty good.

During the time of pneumonia recovery in early 2023 when I wasn't skating, my lower ankles and feet were doing better.  Friction from the skate boot and sweat was halted.  Now that I'm skating again, that area of skin is more activated for patches.  

When a little stress comes along, skin still flares up a bit.  But overall, the change has been for the better since late 2022.  

I saw my dermatologist, yesterday.  She thought my skin was looking better than the last time she'd seen me.  She said she hears about stress and skin from her patients often.  

I don't know how to overcome stressful situations in life.  But it's interesting that the skin is so sensitive to stressors.  

How do you deal with stress?  Have you ever had improvement in your skin when you've resolved a stressful matter?

This study analysed the association of CRH-POMC polymorphisms with psoriasis and evaluated transcript expression of lesional psoriatic and normal skin in RNA-seq data.

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Background:
Skin is a target organ and source of the corticotropin-releasing hormone–proopiomelanocortin (CRH-POMC) system, operating as a coordinator and executor of responses to stress. Environmental stress exacerbates and triggers inflammatory skin diseases through modifying the cellular components of the immune system supporting the importance of CRH-POMC system in the pathogenesis of psoriasis. The aim of this study was to analyze the association of CRH-POMC polymorphisms with psoriasis and evaluate transcript expression of lesional psoriatic and normal skin in RNA-seq data.

Methods:
Samples of 104 patients with psoriasis and 174 healthy controls were genotyped for 42 single nucleotide polymorphisms (SNPs) of CRH-POMC using Applied Biosystems SNPlex™method. The transcript quantification was performed using Salmon software v1.3.0.

Results:
The current study demonstrated the associations between melanocortin 1 receptor (MC1R) polymorphisms rs2228479, rs3212369, dopachrome tautomerase (DCT) polymorphisms rs7987802, rs2031526, rs9524501 and psoriasis in the Tatar population. Very strong association was evident for the SNP rs7987802 in the DCT gene (Pc = 5.95е-006) in psoriasis patients. Additionally, the haplotype analysis provided AT DCT (rs7992630 and rs7987802) and AGA MC1R (rs3212358, 2228479, and 885479) haplotypes significantly associated (Pc ˂0.05) with psoriasis in the Tatar population, supporting the involvement of DCT and MC1R to the psoriasis susceptibility. Moreover, MC1R-203 and DCT-201 expression levels were decreased in psoriasis lesional skin compared with healthy control skin.

Conclusions:
This study is the first to identify genetic variants of the MC1R and DCT genes significantly associated with psoriasis in Tatar population. Our results support potential roles of CRH-POMC system genes and DCT in the pathogenesis of psoriasis.

Hello all, I am interested to know if anyone else has had this experience. The second time I got COVID, I was prescribed Paxlovid. Two days into the medication, every trace of my psoriasis disappeared, but all came back as soon as I finished the medication. If others have had the same experience, we should find a way to make the medical research community aware that they should look into it, but if it was just me, I guess I shouldn't make much of it.

This study evaluated the impact of early disease intervention on clinical responses with Tremfya (guselkumab) treatment in patients with moderate-to-severe plaque psoriasis.

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Background:
Guselkumab is an interleukin (IL)-23 inhibitor with demonstrated efficacy in patients with psoriasis.

Objectives:
Evaluate the impact of early disease intervention on clinical responses following 28 weeks of guselkumab treatment in patients with moderate-to-severe plaque psoriasis. Correlate clinical response and disease duration data with serum biomarker data.

Methods:
GUIDE is a phase IIIb randomized, double-blind, parallel-group, multicentre study of adults with moderate-to-severe plaque psoriasis. In study part 1, patients with a short disease duration (SDD [≤2 years]) or a long disease duration (LDD [>2 years]) received guselkumab 100 mg at Week (W) 0, 4, 12, 20 and 28. Those achieving complete skin clearance from W20–28 were defined as a super responder (SRe). A multivariable logistic regression analysed the association between baseline factors and the likelihood of being an SRe. The relationship between clinical response, disease duration and serum biomarker data was assessed at W0 and 4.

Results:
In total, 880 patients were enrolled (SDD/LDD=40.6%/59.4% patients). More SDD than LDD patients achieved absolute Psoriasis Area and Severity Index (PASI)=0[/b] at W28 (51.8% vs. 39.4%) and were SRes (43.7% vs. 28.1% [overall 34.4%]). SDD patients also achieved PASI=0 quicker than LDD patients (median 141 vs. 200 days). Disease duration and prior biologic use had the greatest impact on becoming an SRe, with no strong association among these independent variables. At baseline, there were no significant differences in the serum biomarker levels of IL-17A, IL-17F, IL-22 and β-defensin 2 between SDD and LDD patients, or between SRe and non-SRe patients. Guselkumab rapidly decreased these markers of systemic inflammation across all patient groups analysed at W4. Guselkumab was well tolerated.

Conclusions:
Guselkumab efficacy was consistent across subpopulations, on the skin and systemically. The proportion of SRes was higher in SDD than LDD patients, indicating early treatment intervention may improve clinical outcomes.

Tremfya (guselkumab) provides sustained improvements across all minimal disease activity domains for adults living with active psoriatic arthritis in phase 3b trial.

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The Janssen Pharmaceutical Companies of Johnson & Johnson today announced new data from the Phase 3b COSMOS clinical trial showing that treatment with TREMFYA® (guselkumab) provided sustainable improvements in all minimal disease activity (MDA)a domains through week 48 in adults living with active psoriatic arthritis (PsA) who previously had an inadequate response to one to two tumor necrosis factor inhibitors (TNFi-IR). In a separate post-hoc analysis of the Phase 3 DISCOVER-1 and DISCOVER-2b clinical trial findings, TREMFYA was shown to be associated with prompt and sustained improvements in all identified determinants. This analysis also identified factors that influenced disagreement between patient and physician global assessments (GA), such as patient-reported pain, physical aspects of health-related quality of life and fatigue. TREMFYA is the first and only fully human selective interleukin (IL)-23 inhibitor therapy approved for the treatment of adult patients living with active PsA. These study results are among 41 company-sponsored abstracts being presented by Janssen at the 2023 Annual European Congress of Rheumatology (EULAR) meeting taking place in Milan, Italy, May 31 - June 3, 2023.

A previous study has shown that sustained MDA is typically only achieved by a minority of patients receiving biologic therapy for active PsA. However, in a post-hoc analysis of the Phase 3b COSMOS clinical trial, TREMFYA provided sustained improvement in all MDA domains from baseline through week 48 in adult patients living with active PsA and who were inadequate responders to one to two TNFis (n=189).

• Overall response rates at week 24 and week 48 were Psoriasis Area and Severity Index (PASI)c (66.8/81.5 percent), Leeds Enthesitis Index (LEI)d (74.5/79.8 percent), swollen joint count (SJC)e (46.2/63.0 percent), patient GA (24.5/39.9 percent), Health Assessment Questionnaire – Disability Index (HAQ-DI)f (26.1/37.0 percent), patient pain (14.7/30.6 percent) and tender joint count (TJC)e (14.7/28.3 percent), respectively.
  
• Physician-reported domains (LEI, PASI and SJC) were achieved faster than patient-driven domains (patient GA, HAQ-DI, patient pain and TJC).
  

“Assessing patient-reported symptoms is a vital part of our research that helps us to address unmet needs and provide treatments that can improve outcomes,” said Laura Coates, M.D., Ph.D., Senior Clinical Research Fellow at the University of Oxford.g “These results advance our understanding of the psoriatic arthritis patient experience and will help healthcare professionals develop individualized treatment plans that can target debilitating symptoms and, ultimately, aim to improve quality of life for people living with psoriatic arthritis.”
The importance of a personalized approach to PsA treatment that prioritizes shared decision-making and open dialogue is reinforced in a separate post-hoc analysis of the Phase 3 DISCOVER-1 and DISCOVER-2 studies, which identified differences between patient GA and physician GA. The results showed that while scores were aligned across most factors, patients weighed pain, fatigue and physical health higher than physicians. TREMFYA was associated with prompt and sustained improvements in all identified determinants, including those driving higher patient versus physician scores, such as patient-reported pain, physical aspects of health-related quality of life, and fatigue.

• At baseline, patient GA and physician GA scores were similar in most instances (61.2 percent) with 23.2 percent of cases characterized by a patient GA score higher than a physician GA score. Higher patient scores meant the patient considered this aspect of their disease to be worse than the physician. 15.7 percent of cases had a physician GA score higher than patient GA.
  
• The proportion of patients with higher patient GA score than physician GA score increased to 39.1 percent at week 24, while the proportion with higher physician GA scores decreased to 11.2 percent.
  
• The main determinant of higher patient scores was patient pain, with additional factors including worse physical health-related quality of life at baseline and worse fatigue at week 24.2 Conversely, physicians emphasized objective disease measures, including SJCs, TJCs and elevated C-reactive protein when assessing patient disease status.
  

“Our continued research underscores Janssen’s commitment to not only provide therapeutic options for psoriatic disease, but also to better understand and support the pressing needs of the patients we serve,” said Terence Rooney, M.D., Ph.D., Vice President, Rheumatology and Maternal-Fetal Immunology Disease Area Leader, Janssen Research & Development, LLC. “Active psoriatic arthritis is a challenging, chronic disease, so these findings have important implications for patients and their providers as they work together to address the full spectrum of disease symptoms, including patient-reported outcomes, with the goal of achieving long-term relief.”

In patients with psoriatic arthritis with prior inadequate response to tumour necrosis factor inhibitors, Bimzelx (bimekizumab) demonstrated sustained joint and skin clearance responses to week 52.

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UCB today announced new long-term 52-week data from three Phase 3 studies – BE COMPLETE with its long-term extension study, BE MOBILE 1 and BE MOBILE 2 – evaluating the efficacy and safety profile of bimekizumab, an inhibitor of IL-17F in addition to IL-17A, in adults with active psoriatic arthritis (PsA), active non-radiographic axial spondyloarthritis (nr-axSpA) and active ankylosing spondylitis (AS), also known as radiographic axSpA (r-axSpA), respectively. These results from the bimekizumab phase 3 program in PsA and axSpA are being presented at the European Congress of Rheumatology, EULAR 2023, in Milan, Italy, May 31–June 3. The safety and efficacy of bimekizumab in PsA, nr-axSpA and r-axSpA have not been established, and it is not approved for use in PsA, nr-axSpA or AS by any regulatory authority worldwide.

“Psoriatic arthritis and axial spondyloarthritis are chronic and progressive inflammatory diseases requiring long-term management. The new long-term bimekizumab data presented at EULAR 2023 showed sustained clinical responses across multiple disease manifestations and patient populations up to one year. These results reinforce our belief in bimekizumab as a potential new future treatment for patients living with psoriatic arthritis and axial spondyloarthritis,” said Emmanuel Caeymaex, Executive Vice President, Immunology and U.S. Solutions, UCB.

Bimekizumab 52-week PsA data: patients with prior inadequate response to tumour necrosis factor inhibitors (TNFi-IR)
Key 52-week results from the BE COMPLETE open-label extension study (BE VITAL) build on the previously announced 16-week results from the BE COMPLETE study and 52-week results from the BE OPTIMAL study.

“The long-term data from BE COMPLETE showed that over six out of 10 patients continuously treated with bimekizumab achieved complete skin clearance and almost one in two had minimal disease activity at week 52. These results complement the previously reported 52-week results from the BE OPTIMAL study and highlight the consistent and sustained response seen with bimekizumab in both biologic-naïve and TNF inhibitor-experienced patients with psoriatic arthritis,” said Professor Iain McInnes, University of Glasgow, College of Medicinal Veterinary and Life Sciences, Glasgow, Scotland. 

• American College of Rheumatology (ACR) 50: At week 52, 51.7 percent of psoriatic arthritis patients (TNFi-IR) continuously treated with bimekizumab (160 mg every four weeks [Q4W]; n=267), and 40.6 percent of patients who switched from placebo to bimekizumab at week 16 (n=133) achieved ACR50.
  
• Complete Skin Clearance (PASI100): At week 52, in patients with baseline psoriasis ≥3 percent body surface area, 65.9 percent of patients continuously treated with bimekizumab (n=176) and 60.2 percent of patients who switched from placebo to bimekizumab at week 16 (n=88) achieved complete skin clearance (PASI100).
  
• Minimal Disease Activity (MDA): At week 52, 47.2 percent (n=126/267) of patients continuously treated with bimekizumab and 33.1 percent (n=44/133) of patients who switched from placebo to bimekizumab achieved MDA.
  

Over 52 weeks, 62.6 percent (n=243/388) of patients treated with bimekizumab had ≥1 treatment emergent adverse event (TEAE) and 5.9 percent (n=23/388) reported a serious TEAE.1 Candida infections were reported by 6.4 percent (n=25/388) of patients receiving bimekizumab with all cases reported as mild or moderate and none reported as systemic.

Amgen today announced new research examining the use of Otezla (apremilast) in psoriatic arthritis.

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MOSAIC Phase 4 Study
Unlike X-ray imaging – commonly used to assess joint damage caused by psoriatic arthritis – MOSAIC used magnetic resonance imaging (MRI), a more sensitive tool for imaging inflammation, which begins early and continues throughout the disease course in joints and entheses (sites where tendons or ligaments attach to bones). MOSAIC evaluated Otezla's effect on joint inflammation and structural progression of psoriatic arthritis measured by MRI.

"MOSAIC is the first study to use MRI to assess inflammation in peripheral joints and entheses in a clinical trial, and shows MRI offers a promising way to measure inflammatory disease activity in patients with this condition," said Professor Mikkel Østergaard, M.D., Ph.D., DMSc, Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, University of Copenhagen in Copenhagen, Denmark. "The results of this study are encouraging, as they provide important insights about Otezla treatment and its efficacy on both clinical and inflammatory manifestations of psoriatic arthritis."

In MOSAIC, a multicenter, single-arm, open-label study, patients with active psoriatic arthritis who were treated with Otezla for 48 weeks had MRI of the hand (contrast-enhanced) performed at baseline, week 24 and week 48. The study evaluated change from baseline in the composite score of hand bone marrow edema (BME), synovitis and tenosynovitis in fingers 2-5, assessed by the psoriatic arthritis MRI score (PsAMRIS) at week 24 (the primary endpoint). Total inflammation score, comprised of BME, synovitis, tenosynovitis and periarticular inflammation in fingers, as well as structural progression, were also assessed.
Patients treated with Otezla had improvements in both clinical and MRI measures of inflammation up to week 48. Detailed findings include:

• Inflammation improved, reflected in the mean change from baseline in the composite inflammation score of BME, synovitis, and tenosynovitis as assessed by PsAMRIS for the full analysis set (n=98), which was -2.32 (-4.73, 0.09) at week 24 and -2.91 (-5.45, -0.37) at week 48. Significant improvements at week 24 and 48 in the per protocol population (n=94) were also observed.
  
• No significant structural progression was observed with Otezla. Total damage score – a measure of disease progression – including bone erosion, showed no significant change at weeks 24 and 48.
  
• In addition, patients with moderate disease activity as measured by Clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) experienced greater reductions in inflammation with Otezla as compared to those with high disease activity.
  
• Common treatment-emergent adverse events were diarrhea (33.6%), nausea (12.3%), headache (10.7%), nasopharyngitis (7.4%) and dyspepsia (6.6%).
  

Findings will be presented Friday, June 2 at 12:10 p.m. CEST: POS0226, Poster Tour Session: Apremilast Reduces Inflammation as Measured by MRI of the Hand in Patients with Psoriatic Arthritis: Primary Results from the Phase 4 MOSAIC Study.

Otezla's Effect on Cardiometabolic Parameters in Psoriatic Arthritis
A second EULAR presentation includes data evaluating the effects of Otezla on cardiometabolic parameters (low- and high-density lipoprotein [LDL, HDL], body mass index [BMI] and HbA1c levels) in 781 patients with psoriatic arthritis at 52 weeks. The post-hoc exploratory analysis of data from five pooled Phase 3 trials (PALACE 1-4, ACTIVE) showed Otezla treatment was associated with improvement in cardiometabolic parameters across psoriatic disease activity groups. Among the findings reported:

• Mean LDL in the overall population at baseline decreased by 2.0 mg/dL on average at week 52; 52.3% of patients moved from the high LDL category (≥160 mg/dL) at baseline to borderline (>129 – <160 mg/dL) or normal (≤129 mg/dL) at week 52; and 38.3% changed from borderline high to normal LDL levels.
  
• Mean BMI was 30.3 kg/m2 in the overall population at baseline and decreased by 0.5 kg/m2 at week 52; 9.0% of patients changed from the obese category (≥30 kg/m2) to the overweight category (25 – <30 kg/m2) and 12.3% of patients changed from the overweight category to the normal category (<25 kg/m2).
  
• 50.4% of patients who had prediabetes changed to normal HbA1c levels and 40.0% moved from diabetes to prediabetes at week 52.
  

Findings will be presented Saturday, June 3 at 10:30 a.m. CEST: POS1527, Poster Session: Effects of Apremilast on Changes in Cardiometabolic Parameters by Diabetes and Obesity Status in Patients with Psoriatic Arthritis.

Bimzelx received positive opinion by the Committee for Medicinal Products for Human Use (CHMP) for use in patients with psoriatic arthritis.

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UCB, a global biopharmaceutical company, today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued positive opinions recommending granting marketing authorization for bimekizumab in the European Union (EU) for the treatment of adults with active axial spondyloarthritis (axSpA) and for adults with active psoriatic arthritis (PsA). AxSpA is an indication that spans both non-radiographic axSpA (nr-axSpA) and ankylosing spondylitis (AS), also known as radiographic axSpA (r-axSpA). If approved by the European Commission (EC), these would represent the second and third indications for bimekizumab in the EU, following its initial approval for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy in August 2021.
 
“The positive CHMP opinion for two new indications for bimekizumab in Europe is a significant step towards our goal of delivering differentiated treatment options to patients. If approved, bimekizumab would be the first treatment for psoriatic arthritis and axial spondyloarthritis that inhibits IL-17F in addition to IL-17A. Positive results from the four Phase 3 clinical studies in PsA and axSpA showed that treatment with bimekizumab consistently resulted in deep levels of response that were rapid and sustained,” said Emmanuel Caeymaex, Executive Vice President, Immunology Solutions and Head of U.S., UCB. 

In active PsA, the CHMP recommended approval of bimekizumab alone or in combination with methotrexate, for the treatment of adults who have had an inadequate response or who have been intolerant to one or more disease-modifying antirheumatic drugs. The CHMP opinion is based on data from the Phase 3 BE COMPLETE and BE OPTIMAL studies recently published in The Lancet.  The two studies met their primary and all ranked secondary endpoints with statistical significance at week 16. Long-term data from BE OPTIMAL showed that bimekizumab demonstrated sustained responses to week 52.

The CHMP positive opinions on bimekizumab in active PsA and active axSpA will be referred to the EC, which will deliver a final decision within approximately two months. The marketing authorization will be valid in all member states of the European Union as well as Iceland, Norway, Northern Ireland and Liechtenstein.
Bimekizumab is currently approved in the European Union for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy.

Affibody’s partner Acelyrin today announced 46 weeks Phase 2 data where izokibep demonstrated high levels of response across psoriatic arthritis disease manifestations.

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The randomized double-blind, placebo-controlled, Phase 2 clinical trial evaluated the safety and efficacy of izokibep dosed 80 mg every two weeks (Q2W) or 40 mg Q2W, versus placebo Q2W, in adult patients with active PsA. The global study assessed various endpoints including the American College of Rheumatology (ACR) response, the Psoriasis Area and Severity Index (PASI) score and the Leeds Enthesitis Index (LEI). At Week 16, the placebo cohort transitioned to 80 mg izokibep Q2W. The trial treatment period continued for up to 46 weeks.
 
"The 46-week data announced by our partner ACELYRIN today demonstrate continued and marked improvements in key areas of psoriatic arthritis including joint pain, skin psoriasis, and enthesitis,” said Nikolai Brun, CMO of Affibody.
 
Through week 46 of this Phase 2 trial, izokibep was generally well-tolerated – in line with previous trials of izokibep. The most common adverse event (AE) was injection site reactions. Injection site reactions were localized reactions, with the majority graded mild-to-moderate in severity, generally 25-30 mm in diameter, and typically presented within the first few injections, after which they declined in incidence. In the trial, one serious adverse event (vulvar cancer) which was determined to be potentially drug-related was observed.
 
The full 46-week data from this trial will be presented at a future scientific meeting. Izokibep is currently being evaluated in an ongoing Phase 2b/3 trial in PsA evaluating a range of doses, including higher doses than in the reported Phase 2 trial.
 
ACR50 response is defined as a 50% improvement in tender and swollen joints, along with improvement in three of these five parameters: patient global assessment of disease activity; physician global assessment of disease activity; patient pain scale; disability/functional questionnaire and decreased concentration of C-reactive protein correlated to inflammation. ACR70 response is defined as a 70% improvement in features noted above for ACR50 response, and is considered by some clinicians to be an indicator of significant control of disease activity. PASI100 response is defined as 100% improvement in skin response, or complete resolution of psoriasis skin lesions. Enthesitis resolution is defined as no active entheseal sites on the Leeds Enthesitis Index (LEI).

Izokibep is a small protein therapeutic designed to inhibit interleukin-17A (IL-17A) with high potency and the potential for robust tissue penetration due to its small molecular size, about one-tenth the size of a monoclonal antibody.

Two year results from a Phase III double-blind, randomized controlled trial of Cosentyx (secukinumab) in children and adolescents with severe chronic plaque psoriasis.

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Background:
Secukinumab has previously demonstrated sustained efficacy and favourable safety for up to 52 weeks in paediatric patients (children and adolescents aged 6 to <18 years) with severe chronic plaque psoriasis (NCT02471144).

Objective:
To investigate the long-term (104 weeks) efficacy and safety of secukinumab.

Methods:
After 52 weeks, patients continued to receive secukinumab low dose (LD [75/150 mg]) or high dose (HD [75/150/300 mg]). Patients on etanercept (0.8 mg/kg) until Week 52 entered follow-up. Data for patients receiving secukinumab LD from the beginning and those switching to secukinumab LD from placebo (‘Any secukinumab’ LD) and patients receiving secukinumab HD from the beginning and those switching to secukinumab HD from placebo (‘Any secukinumab’ HD) are presented. Assessments: Psoriasis Area and Severity Index (PASI) score, PASI (75/90/100) responses, Investigator's Global Assessment modified 2011 (IGA mod 2011) 0/1 response, Children's Dermatology Life Quality Index (CDLQI) score and CDLQI 0/1 response up to Week 104, and, safety up to Week 104 for all patients and up to 4 years for some patients (~320 patient-years [PY] of treatment).

Results:
Secukinumab-treated patients showed sustained PASI 75/90/100 and IGA mod 2011 0/1 responses up to Week 104. Throughout the second year of treatment, efficacy was similar for the ‘Any secukinumab’ LD and HD groups for PASI 75 and IGA mod 2011 0/1 responses. PASI 90/100 responses were mostly comparable between the dose groups up to Week 88, but higher in the ‘Any secukinumab’ HD than the ‘Any secukinumab’ LD group at Week 104. Patients achieved a sustained CDLQI 0/1 response that was similar between the ‘Any secukinumab’ LD (61.1%) and HD (65.0%) groups. Safety data were consistent with the established safety profile of secukinumab.

Conclusion:
Secukinumab demonstrated sustained long-term efficacy (up to 2 years) and a favourable safety profile (~320 PY of treatment) in paediatric patients with severe chronic plaque psoriasis.

Three year data on Humira and Methotrexate vs Humira alone.

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Background:
Anti-drug antibodies (ADA) are formed in patients treated with adalimumab (ADL). This might increase clearance of ADL, potentially causing a (secondary) non-response. Combination therapy of ADL and methotrexate (MTX) reduces ADA levels and has a clinical benefit in rheumatologic diseases. In psoriasis however, the long-term effectiveness and safety have not been studied.

Objectives:
To investigate the three-year follow up data of ADL combined with MTX compared to ADL monotherapy in ADL-naive patients with moderate to severe plaque type psoriasis.

Methods:
We conducted a multicentre RCT in the Netherlands and Belgium. Randomisation was performed by a centralised online randomisation service. Patients were seen every 12 weeks until week 145. Outcome assessors were blinded. We collected data on drug survival, effectiveness, safety, pharmacokinetics and immunogenicity of patients that started ADL combined with MTX compared to ADL monotherapy. We present descriptive analysis and patients were analysed according to the group initially randomised to. Patients becoming non-adherent to the biologic were excluded from analyses.

Results:
Sixty-one patients were included and 37 patients (ADL group n=17, ADL+MTX group n=20) continued in the follow-up study after one year. After 109 weeks and 145 weeks, there was a trend towards longer drug survival in the ADL+MTX group compared to the ADL group (week 109: 54.8% vs. 41.4%; p=0.326, week 145: 51.6% vs. 41.4%; p=0.464). At week 145, 7/13 patients were treated with MTX. In the ADL group, 4/12 patients that completed the study developed ADA, and 3/13 in the ADL+MTX group.

Conclusions:
In this small study, there was no significant difference in ADL overall drug survival when it was initially combined with MTX, compared to ADL alone. Discontinuation due to adverse events was common in the combination group. To secure accessible healthcare, combination treatment of ADL and MTX can be considered in individual patients.

Exploring the role and mechanism of lysophosphatidylcholine (LPC) on the pathogenesis of psoriasis.

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Background:
Although abnormal metabolism plays a critical role in the pathogenesis of psoriasis, the details are unclear.

Objectives:
Here, we identified to explore the role and mechanism of lysophosphatidylcholine (LPC) on the pathogenesis of psoriasis.

Methods:
The level of LPC in plasma and skin lesions and the expression of G2A on skin lesions of psoriasis patients were detected by enzyme-linked immunosorbent assay, liquid chromatography-tandem mass spectrometry, or immunohistochemistry, respectively. The glycolysis in the skin lesions of imiquimod (IMQ)-induced psoriasis-like mouse model was detected by extracellular acidification rate. LPC was subcutaneously injected into IMQ-treated mouse ears, and the phenotype as well as the glycolysis were evaluated. Exploring the effects and mechanism of LPC on keratinocytes and CD4+ T cells by culturing primary keratinocytes and CD4+ T in vitro.

Results:
We found that LPC was significantly increased both in the plasma and skin lesions of psoriatic patients, while G2A, exerting an essential role in LPC inducing biological functions, was increased in psoriatic lesions. The abundance of LPC was positively correlated with glycolytic activity in the psoriasis-like mouse model. LPC treatment facilitated psoriasis-like inflammation and glycolytic activity in skin lesions. Mechanistically, the LPC/G2A axis significantly triggered glycolytic activity and produced inflammatory factors in keratinocytes, and blockade of glycolysis abrogated LPC-induced expression of inflammatory mediators in keratinocytes. LPC activated STAT1, resulting in recognition and binding to the promoters of GCK and PKLR, which are glycolytic rate-limiting enzymes. Furthermore, the LPC/G2A axis directly benefited Th1 differentiation, which was dependent on LPC-induced glycolytic activity. Notably, LPC indirectly facilitated Th17 differentiation by inducing the secretion of IL-1β in keratinocytes-T cells coculture system.

Conclusions:
Taken together, our findings revealed the role of the LPC/G2A axis in the pathogenesis of psoriasis; targeting LPC/G2A is a potential strategy for psoriasis therapy.

Does anyone getting jabs delivered in the uk know what the deal is with these firms?

As far as I can see they are two separate firms (sciensus used to be healthcare at home)
But they both contact me to try and arrange my delivery - one you can do online, the other wants you to use an app.

I’ve arranged this delivery with one of the firms, but was curious so I asked my derm nurse whether two different firms were both trying to deliver my jabs.

They answered by telling me the firm I was set up to get my jabs from - without answering my question about who the other guys are - anyone know anything more cos I think it’s weird.

This study evaluated the risk of first occurrence and recurrence of uveitis in patients with psoriasis in the Korean population.

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Background:
Evidence for the association between psoriasis and uveitis according to the severity of psoriasis including psoriatic arthritis (PsA) and type of uveitis is lacking, and there are no data on the frequency or timing of recurrence of uveitis in patients with psoriasis.

Objectives:
We aimed to evaluate the risk of first-occurrence and recurrence of uveitis in patients with psoriasis in the Korean population. We further evaluated the risk of uveitis according to the severity of psoriasis, comorbidity of PsA, and location of uveitis.

Methods:
In a nationwide retrospective cohort study, we compared 317,940 adult patients who had psoriasis with 635,880 matched controls. Incidence rates (IRs) and estimated IR ratios of the first occurrence and recurrence of uveitis were calculated using survival analysis and Poisson regression, respectively.

Results:
The rate of uveitis incidence and uveitis recurrence in patients with psoriasis were 1.18 and 2.31 per 1,000 person-years, respectively. Compared with the controls, the IR ratios of development and recurrence of uveitis in patients with psoriasis were 1.14 (95% CI 1.08, 1.2) and 1.16 (95% CI 1.12, 1.21), respectively. The recurrence rate of uveitis was highest within 3 years after the onset of psoriasis. The corresponding IR ratios for uveitis recurrence in patients with mild psoriasis, severe psoriasis, and PsA were 1.11 (1.06, 1.16), 1.24 (1.16, 1.33), and 1.49 (1.31, 1.7), respectively. Patients with psoriasis had an increased risk of recurrence of anterior uveitis, and patients with both psoriasis and PsA had an increased risk of recurrence of both anterior and pan-uveitis.

Conclusions:
Patients with psoriasis had a higher risk of both development and recurrence of uveitis, especially with severe psoriasis and PsA. The timing of uveitis recurrence was related to the onset of psoriasis, and patients who had psoriasis with PsA had an increased risk of vision-threatening pan-uveitis.

Understand the connection between psoriasis and cardiovascular disease.

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Background:
Psoriasis is an inflammatory skin disease associated with increased cardiovascular (CV) risk, whose pathogenesis is not fully known.

Objective:
We identified a transcriptomic signature in psoriasis and investigated its association with prevalent and future risk of a CV event to understand the connection between psoriasis and CV disease (CVD).

Methods:
Psoriasis patients (n=37) with a history of moderate-severe skin disease without CVD and 11 matched controls underwent whole blood RNA sequencing. This transcriptomic signature in psoriasis vs controls was evaluated in two CVD cohorts: Women referred for cardiac catheterization with (n=76) vs without (n=97) myocardial infarction (MI), and patients with peripheral artery disease (n=106) followed over 2.5 years for major adverse CV or limb events (MACLE). The association between genes differentially expressed in psoriasis and prevalent and incident CV events was assed.

Results:
In psoriasis, median age was 44 (IQR; 34 – 51) years, 49% male, and ACC/AHA ASCVD Risk Score of 1.0% (0.6 – 3.4) with no significant difference vs controls. The median psoriasis area and severity index score (PASI) was 4.0 (IQR 2.9 – 8.2) with 36% on biologic therapy. Overall, 247 whole blood genes were upregulated and 228 downregulated in psoriasis vs controls (p<0.05), and 1,302 genes positively and 1,244 genes negatively correlated with PASI (p<0.05). Seventy-three genes overlapped between psoriasis prevalence and PASI with key regulators identified as IL-6, IL-1β, and interferon gamma. In the CVD cohorts, 50 of 73 genes (68%) identified in psoriasis associated with prevalent MI, and 29 (40%) with incident MACLE. Key regulator transcripts identified in psoriasis and CVD cohorts included SOCS3, BCL3, OSM, PIM2, PIM3, and STAT5A.

Conclusions:
A whole blood transcriptomic signature of psoriasis diagnosis and severity associated with prevalent MI and incident MACLE. These data have implications for better understanding the link between psoriasis, systemic inflammation, and CVD.

This study looked at the effect of biologic therapy in HIV patients with psoriasis.

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Background:
Psoriasis is a chronic immune mediated inflammatory disorder which also occurs in the setting of HIV. Biologic therapy has transformed the treatment landscape for psoriasis however individuals with HIV are excluded from clinical trials. The impact of biologic therapy upon blood parameters in HIV is unclear and only observed in small case series.

Objective:
To assess the effect of biologic therapy in psoriasis vulgaris in individuals with well controlled HIV, upon CD4+ cell counts, CD4+ proportion and HIV Viral load over 12 months.

Methods:
This retrospective cohort study was conducted at a tertiary referral centre in Sydney, Australia and included 36 HIV-positive individuals with psoriasis treated with biologic therapy, compared to 144 age, gender and HAART-matched individuals without psoriasis seen between 2010-2022. Outcomes of interest included HIV Viral Load, CD4+ cell count and incidence of infections.

Results:
No statistically significant difference was seen in baseline HIV Viral load and CD4+ count between individuals with psoriasis and without psoriasis. No significant change in CD4+ count or HIV Viral load was seen over the 12-month period of analysis in the HIV cohort without psoriasis. The HIV cohort treated with biologic therapy for psoriasis also did not demonstrate any significant change in HIV Viral load and CD4+ counts over the 12-month period examined. Stratification by type of biologic therapy used did not identify any significant changes in these parameters. Rates of infections and adverse events were also not significantly different between cohorts. It is possible that minor blips seen in the biologics cohort may be a risk factor for future virological failure, and future prospective longitudinal studies are required.

Conclusions:
In individuals with well controlled HIV, the use of biologic therapy for psoriasis does not significantly impact HIV Viral load, CD4+ cell count, CD4+ proportion and rates of infection over the first 12 months of therapy.