Physician Global Assessment Research Articles

Efficacy and safety of subcutaneous spesolimab for the prevention of generalised pustular psoriasis flares (Effisayil 2): an international, multicentre, randomised, placebo-controlled trial

Spesolimab is an anti-interleukin-36 receptor monoclonal antibody approved to treat generalised pustular psoriasis (GPP) flares. We aimed to assess the efficacy and safety of spesolimab for GPP flare prevention. This multicentre, randomised, placebo-controlled, phase 2b trial was done at 60 hospitals and clinics in 20 countries. Eligible study participants were aged between 12 and 75 years with a documented history of GPP as per the European Rare and Severe Psoriasis Expert Network criteria, with a history of at least two past GPP flares, and a GPP Physician Global Assessment (GPPGA) score of 0 or 1 at screening and random assignment. Patients were randomly assigned (1:1:1:1) to receive subcutaneous placebo, subcutaneous low-dose spesolimab (300 mg loading dose followed by 150 mg every 12 weeks), subcutaneous medium-dose spesolimab (600 mg loading dose followed by 300 mg every 12 weeks), or subcutaneous high-dose spesolimab (600 mg loading dose followed by 300 mg every 4 weeks) over 48 weeks. The primary objective was to demonstrate a non-flat dose-response curve on the primary endpoint, time to first GPP flare. From June 8, 2020, to Nov 23, 2022, 157 patients were screened, of whom 123 were randomly assigned. 92 were assigned to receive spesolimab (30 high dose, 31 medium dose, and 31 low dose) and 31 to placebo. All patients were either Asian (79 [64%] of 123) or White (44 [36%]). Patient groups were similar in sex distribution (76 [62%] female and 47 [38%] male), age (mean 40·4 years, SD 15·8), and GPP Physician Global Assessment score. A non-flat dose-response relationship was established on the primary endpoint. By week 48, 35 patients had GPP flares; seven (23%) of 31 patients in the low-dose spesolimab group, nine (29%) of 31 patients in the medium-dose spesolimab group, three (10%) of 30 patients in the high-dose spesolimab group, and 16 (52%) of 31 patients in the placebo group. High-dose spesolimab was significantly superior versus placebo on the primary outcome of time to GPP flare (hazard ratio [HR]=0·16, 95% CI 0·05-0·54; p=0·0005) endpoint. HRs were 0·35 (95% CI 0·14-0·86, nominal p=0·0057) in the low-dose spesolimab group and 0·47 (0·21-1·06, p=0·027) in the medium-dose spesolimab group. We established a non-flat dose-response relationship for spesolimab compared with placebo, with statistically significant p values for each predefined model (linear p=0·0022, emax1 p=0·0024, emax2 p=0·0023, and exponential p=0·0034). Infection rates were similar across treatment arms; there were no deaths and no hypersensitivity reactions leading to discontinuation. High-dose spesolimab was superior to placebo in GPP flare prevention, significantly reducing the risk of a GPP flare and flare occurrence over 48 weeks. Given the chronic nature of GPP, a treatment for flare prevention is a significant shift in the clinical approach, and could ultimately lead to improvements in patient morbidity and quality of life. Boehringer Ingelheim.

Efficacy of Guselkumab in Treating Nails, Scalp, Hands, and Feet in Patients with Psoriasis and Self-reported Psoriatic Arthritis.

The aim of this study was to evaluate guselkumab efficacy on regional psoriasis in a subset of psoriasis patients with a self-reported psoriatic arthritis (PsA) diagnosis. In the phase 3 VOYAGE-1 and -2 studies, at week (W)0, patients with moderate-to-severe psoriasis were randomized to guselkumab 100mg, placebo → guselkumab 100mg at W16 through W44, or adalimumab 80mg then 40mg at W1 through W48 (VOYAGE-1) or W24 (VOYAGE-2). Pooled efficacy outcomes, including scalp-specific Investigator's Global Assessment (ss-IGA), hands and/or feet Physician's Global Assessment (hf-PGA), fingernail PGA (f-PGA), Nail Psoriasis Area and Severity Index (NAPSI), and Dermatology Life Quality Index (DLQI), were compared (nominal p-values) through W24 in patients with self-reported PsA diagnosis. Response rates/percentage improvement from baseline were determined, employing treatment failure rules and non-response/no improvement data imputation. A total of 76, 153, and 106 psoriasis patients with self-reported PsA were randomized to the placebo, guselkumab, or adalimumab groups, respectively; the baseline characteristics of patients in all three arms were comparable. At W16, a greater proportion of guselkumab- versus placebo-treated patients achieved ss-IGA 0/1 (80.6% vs. 22.7%, p < 0.001), hf-PGA 0/1 (68.9% vs. 14.8%, p < 0.001), f-PGA 0/1 (47.6% vs. 17.0%, p < 0.001), and DLQI 0/1 (45.6% vs. 2.7%, p < 0.001) responses; mean percentage NAPSI improvement was also greater with guselkumab (39.5% vs. 6.5%, p < 0.001). At W24, patients receiving guselkumab had higher ss-IGA 0/1 (77.5% vs. 58.5%, p = 0.003) and DLQI 0/1 (47.7% vs. 34.3%, p = 0.024) response rates versus those receiving adalimumab. Response rates/mean percentageimprovements at W48 (VOYAGE-1) were numerically greater with guselkumab than adalimumab (e.g., NAPSI improvement: 75.6% vs. 60.9%). Guselkumab-treated patients with psoriasis and self-reported PsA showed meaningful improvements in nail, scalp, and palmoplantar psoriasis. VOYAGE-1 (ClinicalTrials.gov Identifier: NCT02207231) and VOYAGE-2 (ClinicalTrials.gov Identifier: NCT02207244).

Tapinarof Cream 1% Once Daily for the Treatment of Plaque Psoriasis: Case Photography of Clinical Outcomes from Three Phase3 Trials.

Tapinarof cream 1% (VTAMA®; Dermavant Sciences, Inc.) is a non-steroidal, topical, aryl hydrocarbon receptor agonist approved by the US Food and Drug Administration (FDA) to treat plaque psoriasis in adults and under investigation for the treatment of psoriasis in children down to 2years of age, and for atopic dermatitis in adults and children down to 2years of age. The PSOARING phase3 clinical trial program evaluated tapinarof cream 1% once daily (QD) in adults with mild to severe plaque psoriasis for up to 52weeks (NCT03956355, NCT03983980, NCT04053387). Here we present case photography documenting outcomes in the PSOARING trials. Cases illustrate various outcomes across different body areas, including responses meeting the formal FDA-mandated regulatory endpoint of a Physician Global Assessment (PGA) score of 0 (clear) or 1 (almost clear) and a decrease of at least 2points from baseline at week12, meaningful clinical improvement not meeting this formal endpoint, patient-reported outcomes, and pre-specified adverse events of special interest (AESIs). Tapinarof cream 1% QD demonstrated rapid and highly statistically significant efficacy, with improvements in disease activity and quality of life. In addition, a high rate (40.9%; n = 312/763) of complete disease clearance (PGA = 0) was achieved, and improvements exceeding National Psoriasis Foundation treatment goals were demonstrated. After first achieving complete disease clearance (PGA = 0), patients treated with tapinarof experienced an approximately 4-month remittive effect off therapy. Incidence and severity of folliculitis and contact dermatitis AESIs were generally mild or moderate, localized to the site of application, and associated with low discontinuation rates. Medical images are of importance in trials of dermatologic therapies to inform clinical decision-making and enhance patient assessment. Tapinarof cream 1% QD is efficacious and well tolerated in patients with mild to severe plaque psoriasis, with clinically relevant improvements seen early in the course of treatment.Clinicaltrials.gov numbers: NCT03956355, NCT03983980, NCT04053387.

Defining the physician global assessment threshold equivalent to remission in patients with systemic lupus erythematosus.

The optimal threshold of the physician global assessment (PGA) for remission in SLE has never been evaluated systematically. The aim of this study was to assess the ideal PGA threshold associated with physician remission and to investigate its impact on remission rates in our lupus cohort. In this monocentric cross-sectional study, patients with SLE were evaluated for physician remission by asking the treating physicians whether they considered their patient to be in remission, regardless of objective remission criteria. Furthermore, two objective remission definitions were applied: (i) DORIS (Definition Of Remission In Systemic Lupus Erythematosus) remission using a PGA of <2 (0-10) (corresponding to <0.5 on a visual analogue scale 0-3 used in DORIS); and (ii) DORIS remission with omission of PGA (modDORIS). A receiver operating characteristic analysis and regression analyses were performed to assess the ideal PGA threshold and factors influencing PGA. Of the 233 patients included, 126 patients (54.0%) were in physician remission, 42.5% in DORIS remission and 67.0% in modDORIS remission. A PGA of <2 [numeric rating scale (NRS) 0-10] had the highest sensitivity (79%) and specificity (81%) for physician remission and modDORIS (area under the curve 0.85 and 0.69). PGA of patients fulfilling any of the remission definitions was associated with pain and hypocomplementemia. Damage was numerically higher in patients in modDORIS only; no association between PGA and damage was found in regression analysis. Using a PGA threshold of <2 (0-10), corresponding to <0.6 (0-3), resulted in best prediction of physician remission. PGA levels seem to be influenced by pain and complement levels but not disease damage.

Patient and physician assessment in difficult-to-treat rheumatoid arthritis: patterns of subjective perception at early stages of b/tsDMARD treatment

ObjectivesTo analyse the trajectories of Disease Activity Score 28 (DAS28), patient global assessment (PGA) and physician global assessment (PhGA) and to assess their predictive capabilities on difficult-to-treat rheumatoid arthritis (D2TRA)...

Baseline Peripheral Blood Mononuclear Cell Transcriptomics Before Ustekinumab Treatment Is Linked With Crohn's Disease Clinical Response at 1 Year.

Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin (IL)-12 and IL-23, is used for Crohn's disease (CD), and the documented clinical remission rate after 1 year was observed in approximately 50% of patients. We aimed to identify predictors for a clinical response using peripheral blood obtained from patients with CD just before ustekinumab treatment initiation. RNA extraction from peripheral blood mononuclear cells was followed by mRNA paired-end sequencing. Differential gene expression was performed using DESeq2. We processed samples from 36 adults with CD (13 men, 36%) obtained at baseline before starting ustekinumab treatment. Twenty-two of 36 (61%) were defined as responders and 14/36 (39%) as nonresponders after 1 year based on Physician Global Assessment. Differential gene expression between responders (n = 22) and nonresponders (n = 14) did not show a gene expression signature that passed false discovery rate (FDR) correction. However, the analyses identified 68 genes, including CXCL1/2/3, which were induced in nonresponders vs responders with P < 0.05 and fold change above 1.5. Functional annotation enrichments of these 68 genes using ToppGene indicated enrichment for cytokine activity (FDR = 1.98E-05), CXCR chemokine receptor binding (FDR = 2.11E-05), IL-10 signaling (FDR = 5.03E-07), genes encoding secreted soluble factors (FDR = 1.73E-05), and myeloid dendritic cells (FDR = 1.80E-08). No substantial differences were found in peripheral blood mononuclear cell transcriptomics between responders and nonresponders. However, among the nonresponders, we noted an increased inflammatory response enriched for pathways linked with cytokine activity and chemokine receptor binding and innate myeloid signature. A larger cohort is required to validate and further explore these findings.

41625 Tapinarof Cream 1% Once Daily (QD) for Plaque Psoriasis: Post Hoc Analysis of Physician Global Assessment x Body Surface Area (PGAxBSA) Composite for the PSOARING 1 and 2 Trials

41625 Tapinarof Cream 1% Once Daily (QD) for Plaque Psoriasis: Post Hoc Analysis of Physician Global Assessment x Body Surface Area (PGAxBSA) Composite for the PSOARING 1 and 2 Trials

Real-World Safety and Effectiveness of Fluticasone Furoate/Vilanterol in Patients with Asthma and/or Chronic Obstructive Pulmonary Disease: A Post-Marketing Study in Korea.

Fluticasone furoate/vilanterol (FF/VI; RELVAR ELLIPTA) is approved in Korea for patients with asthma or chronic obstructive pulmonary disease (COPD). This study evaluated the effectiveness and safety of FF/VI in Korean patients with asthma and/or COPD over a 6-year period. This was an open-label, multicentre, observational, post-marketing surveillance study in patients newly treated with FF/VI (100 or 200 μg/25 μg once daily). Safety endpoints were the incidence of adverse events (AEs), including unexpected AEs/adverse drug reactions (ADRs) and serious AEs/ADRs. Effectiveness was assessed after 24 weeks by Global Physician Assessment (logistic regression) and forced expiratory volume in 1 s (FEV1; paired t-tests). Of the 3426 patients enrolled across 45 hospitals between July 2014 and June 2020, 3216 were included in the safety analysis (50.5% female; mean age ± standard deviation [SD]: 58.6 ± 16.3 years). Overall incidence of AEs was 30.9% (n = 992); 4.1% (n = 132) were ADRs. Serious AEs were reported in 4.1% (n = 132) of patients; 0.1% (n = 4) were ADRs. Of 1543 patients analysed for symptomatic improvement, 89.2% (n = 1377) improved, 9.4% (n = 145) were unchanged, and 1.4% (n = 21) worsened. Mean FEV1 (difference ± SD) increased significantly in patients with asthma (0.09 ± 0.29 L; p < 0.0001), COPD (0.11 ± 0.24 L; p = 0.0011), or both (0.05 ± 0.18 L; p = 0.0399), indicating improved lung function. In this real-world study, FF/VI administered to Korean patients was well tolerated and effective for the treatment of asthma and COPD. These results were consistent with other studies in Asian and global populations.

Anxiety and depression in rheumatoid arthritis patients: prevalence, risk factors and consistency between the Hospital Anxiety and Depression Scale and Zung's Self-rating Anxiety Scale/Depression Scale.

The aim was to explore the prevalence and independent risk factors for anxiety and depression in RA patients and to assess the consistency between the hospital anxiety and depression scale (HADS) and Zung's self-rating anxiety scale/depression scale (SAS/SDS). In total, 160 RA patients and 60 healthy controls (HCs) were enrolled consecutively, and HADS and SAS/SDS were completed. The HADS-defined anxiety rate, HADS-defined depression rate, SAS-defined anxiety rate and SDS-defined depression rate were 36.9, 36.3, 29.4 and 29.4%, respectively, in RA patients, all of which were much higher in RA patients than in HCs (all P < 0.001). A relatively high consistency was observed between HADS-defined anxiety and SAS-defined anxiety (κ = 0.551, P < 0.001) and between HADS-defined depression and SDS-defined depression (κ = 0.563, P < 0.001) in RA patients. Interestingly, screened by multivariate logistic regression analyses, single/divorced/widowed marital status, swollen joint count, disease duration, ESR, physician's global assessment (PhGA) and DAS28 were independently correlated with HADS-defined or SAS-defined anxiety risk in RA patients; meanwhile, female biological sex, single/divorced/widowed marital status, rural location, disease duration, PhGA and DAS28 were independently associated with HADS-defined or SDS-defined depression risk in RA patients. Anxiety and depression are highly prevalent in RA patients and are independently correlated with single/divorced/widowed marital status and higher disease activity. In addition, the HADS presents a high consistency with the SAS/SDS with many fewer questions, which might be more suitable for long-term assessment of RA.

Different Biomarkers of Response to Treatment with Selective Jak-1 Inhibitors in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease that causes progressive joint damage. The Janus kinase (JAK) inhibitors (JAK-I) represent a new therapeutic option for RA patients, blocking the intracellular JAK-STAT pathway. Today, no studies have been conducted to determine whether new biomarkers could better reflect disease activity in patients treated with JAK-I than traditional disease activity indicators. Thus, the aim of our study was to determine additional disease activity biomarkers in RA patients receiving selective JAK-1 inhibitors. we enrolled 57 patients with RA: 34 patients were treated with Upadacitinib (UPA) and 23 patients with Filgotinib (FIL). All patients were evaluated for clinimetry with DAS28 and Crohn's Disease Activity Index (CDAI), number of tender and swollen joints, Visual Analogic Scale (VAS), Physician Global Assessment (PhGA), and Health Assessment Questionnaire (HAQ), at baseline and at the 12th week of treatment. Lymphocyte subpopulations, complete blood count, erythrocyte sedimentation rate (ESR), C-Reactive Protein (CRP), anti-cyclic citrullinated peptide antibodies (APCA), rheumatoid factor (RF) IgM, interleukin 6 (IL-6), circulating calprotectin (cCLP), tumor necrosis factor α (TNFα), soluble urokinase Plasminogen Activator Receptor (suPAR), complement functional activity were measured at baseline and after the 12th week of treatment. in both groups of patients, we documented a significant reduction in the clinimetric parameters DAS28, CDAI, number of tender joints, number of swollen joints, VAS, PhGA, and HAQ. Moreover, significant differences were reported for laboratory parameters of ESR, CRP, IL-6, suPAR, cCLP, and PLT/L ratio in both groups. However, no difference was demonstrated between the two groups for changes in renal, hepatic, and lipid parameters. the suPAR and cCLP levels may lead towards a different therapeutic choice between UPA and FIL, with the expression of two different RA pathophenotypes directing FIL towards a lymphocyte-poor form and UPA towards a myeloid form of RA.

Six-Month Persistence and Multi-domain Effectiveness of Guselkumab in Adults with Psoriatic Arthritis: Real-World Data from the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.

The aim of this work is to evaluate treatment persistence and clinical outcomes after 6months of on-label guselkumab use in patients with rheumatologist-diagnosed active psoriatic arthritis (PsA) enrolled in the CorEvitas PsA/Spondyloarthritis Registry. Participants with PsA who initiated and persisted with on-label guselkumab use post-Food and Drug Administration (FDA) approval for active PsA (7/13/2020; subcutaneous 100mg at weeks 0, 4, and every 8weeks) at their 6-month follow-up visit (occurring through 3/31/2023) comprised the primary analysis population (On-Label Persisters). Hierarchical, multiplicity-controlled primary and secondary outcomes were mean (95% confidence interval) changes from baseline at 6months in clinical Disease Activity Index for PsA (cDAPSA; primary), Physician Global Assessment (PGA) of arthritis and psoriasis (visual analog scale [VAS] 0-100), patient-reported pain (VAS 0-100), and percent body surface area with psoriasis (%BSA). Paired ttests determined changes that were statistically significantly different from 0 (α = 0.05). Among 114 patients who initiated on-label guselkumab and had eligible baseline and 6-month visits, 90 (78.9%) had persistent use. Among these On-Label Persisters at baseline, mean duration of PsA symptoms = 13.6years; mean cDAPSA, PGA, and patient-reported pain = 22.0, 42.3, and 57.0, respectively; 94.4% had a history of psoriasis (mean BSA 7.6%); and 18.9% and 73.3%, respectively, previously received 1 or ≥ 2 biologic/targeted synthetic disease-modifying antirheumatic drugs. The mean change (improvement) in cDAPSA was -5.4 (-8.5, -2.3; p < 0.001) at 6months. Significant mean improvements in PGA (-19.0 [-24.2, -13.8]), patient-reported pain (-9.1 [-14.4, -3.8]), and %BSA (-5.1 [-7.6, -2.7]) were also observed (all p < 0.001). In this real-world PsA population, generally characterized by longstanding, treatment-resistant, active disease at baseline, persistent guselkumab use in nearly 80% of patients with on-label use was accompanied by significant improvements in joint and skin symptoms and patient-reported pain at 6months. These registry data support results from randomized clinical trials demonstrating the efficacy of guselkumab in improving PsA signs and symptoms. clinicaltrials.gov: NCT02530268.

Noncorticosteroid Topical Therapies for the Treatment of Plaque Psoriasis: A Narrative Review.

Objective: The objective was to compare the safety and efficacy of noncorticosteroid topical treatments for plaque psoriasis. Data Sources: A literature search of the PubMed database was performed (January 1978 to May 2023) using the keywords plaque psoriasis, tapinarof, benvitimod, Vtama, roflumilast, Zoryve, pimecrolimus, tacrolimus, tazarotene, tacalcitol, calcitriol, Vectical, calcipotriene, Dovonex, tacalcitol, vitamin D analogs, salicylic acid, non-corticosteroid topical, Investigator's Global Assessment, and Physician's Global Assessment. Study Selection and Data Extraction: Relevant English-language articles and clinical trial data were considered. Data Synthesis: Six noncorticosteroid topical classes for the treatment of plaque psoriasis were selected. The percentage of patients with plaque psoriasis who achieved Investigator's Global Assessment (IGA) success after 8 weeks of treatment with tacalcitol, calcipotriene/betamethasone dipropionate compound, tazarotene/halobetasol propionate, and roflumilast was 17.9%, 39.9%, 40.7%, and 42.4%, respectively. For 12-week trials of tapinarof and coal tar, 37.4% and 58.2% of patients achieved IGA success, respectively. There were 48% and 71.4% reductions in IGA scores with salicylic acid (12 weeks) and pimecrolimus (4 weeks), respectively. Finally, 66.7% of patients achieved Physician's Global Assessment success with 8 weeks of tacrolimus. There were no serious adverse events for the noncorticosteroid topicals. Conclusion: Noncorticosteroid topicals are suitable options for patients with plaque psoriasis who would like to avoid topical corticosteroids or have experienced adverse effects from chronic corticosteroid use. Due to treatment duration differences and varied outcome measures, it is unclear which noncorticosteroid topical is most efficacious; however, calcineurin inhibitors appear to exhibit the greatest efficacy. Each topical was efficacious in treating plaque psoriasis and had an adequate safety profile. Despite several treatment options for plaque psoriasis, medication adherence is a limiting factor.

Assessment of racial and ethnic differences of atopic dermatitis severity and treatment patterns in a diverse outpatient cohort in the United States: a retrospective observational study.

Previous population-based studies in the United States found racial/ethnic differences of atopic dermatitis (AD) severity and treatment patterns. It is unclear whether these differences are from differences of disease characteristics or disparities. To examine racial/ethnic differences in severity and treatment patterns in a diverse outpatient patient cohort of AD patients (n = 833). There were no significant associations of highest-reported body surface area (BSA; Fisher's exact test, P = 0.19 and P = 0.44) or physician's global assessment (PGA; P = 0.63 and P = 0.57) with race or ethnicity; nor interactions of race/ethnicity with gender or age as predictors of BSA or PGA. Asian and multiracial/other patients were more likely than White or Black patients to use topical calcineurin inhibitors (Chi-square, P = 0.01). Dupilumab use differed by race (Multiracial/other = 35.0%; White = 20.1%; Asian = 15.7%; Black = 13.6%; Chi-square, P = 0.03), but not ethnicity (P = 0.88). Use of oral corticosteroids (Chi-square, P = 0.74), immunosuppressants (P = 0.98) or GABAergics (P = 0.16) or NBUVB (P = 0.42) did not differ by race. There were no interactions of race/ethnicity with gender or age as predictors of treatment use. Similar treatment patterns were observed across racial/ethnic groups. Though, topical calcineurin inhibitors were more commonly used in Asian and multiracial/other patients; dupilumab use was more common in multiracial/other patients.

Clinical and patient-reported outcomes from the first 4 years of a Psoriasis Biologics Registry in Singapore.

Interim analysis of the National Skin Centre Singapore Psoriasis Biologics Registry (SINGPSOR) from August 2017 to May 2021, in which 58 patients were analysed, showing that those receiving biologic treatment had significantly more severe psoriasis based on PASI (Psoriasis Area and Severity Index), BSA (body surface area) and PGA (Physician Global Assessment) measures at baseline, demonstrated a statistically non-significant trend towards greater improvement with treatment, and had a lower percentage of adverse events compared to those receiving conventional systemic therapy. Future analyses of SINGPSOR, with larger sample size and longer follow-up, will be invaluable to further characterize these patients and their treatment outcomes.

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ZY-IL1 in Three Patients with Cryopyrin-Associated Periodic Syndromes.

We present the first results of the proof-of-concept phase 2a study of oral NLRP3 inflammasome inhibitor in subjects with cryopyrin-associated periodic syndromes (CAPS). Three adult subjects with a confirmed diagnosis of CAPS were enrolled and administered 50mg of ZYIL1 twice daily for 7 days. A total of 5 treatment-emergent adverse events (TEAEs) were reported in 2 subjects. All 5 TEAEs were mild in severity and considered unrelated to the study drug. At steady state, the average plasma concentration and trough concentration ranged from 2.5 to 4.2 and 1.4 to 2.5µg/mL, respectively. Inflammatory markers and disease activity (physician and patient global assessment score) decreased notably 12 hours post-last dose.

Efficacy and safety of the combination of tranexamic acid injection and electro-optical synergy (ELOS) versus tranexamic acid injection alone in the treatment of melasma.

Melasma is a common, relapsing, multifactorial disease for which the treatment decision remains extremely difficult. This study was designed to compare the efficacy and safety of the combination of tranexamic acid(TA) injection and electro-optical synergy (ELOS) versus TA injection alone in treating melasma.A retrospective study was undertaken for patients with facial epidermal or mixed-type melasma to compare clinical data between 15 patients receiving a combination regimen and 15 patients with TA injection only. The study administeredTA through intravenous injection to the combination group (twice weekly for 12weeks) followed by ELOS therapy (once a month for three times). The TA group, on the other hand, received only TA injection (twice weekly for 12weeks). The evaluation of clinical effectiveness was based on comparing the Melasma Area Severity Index (MASI) scores before and one month after treatment (at 4months). The Physician Global Assessment (PGA) and Patient satisfaction were documented, and adverse reactions were recorded. All patients were followed up for one year to observe the relapse.After treatment, the MASI scores and melasma severity were significantly reduced in both groups. The combination group showed better efficacy than the TA only group (P< 0.05). The Physician Global Assessment (PGA) and Patient satisfaction showed superior efficacies of the combination group. No significant difference was observed between the two groups in terms of treatment-related side effects. Both groups experienced a certain degree of recurrence during the one-year follow-up, but the TA only group had a significantly higher recurrence rate than the combination group (P < 0.01).Together, the combination of TA injection and ELOS is a safe and effective treatment strategy for melasma and should be promoted.

A Retrospective Study on Clinical Experience with Tofacitinib in the Treatment of Rheumatoid Arthritis at a Tertiary Care Center

Abstract Introduction: Tofacitinib is the first oral Janus kinase (JAK) inhibitor approved for the treatment of rheumatoid arthritis (RA). Since the expiry of its patent, the drug has become affordable to patients in India. The present study describes our experience with tofacitinib in patients with RA. Objective: To retrospectively study the 6-month outcome of patients with RA treated with tofacitinib. Methods: We retrieved the records of all consecutive patients with RA who were commenced on tofacitinib in the rheumatology clinic of our tertiary care hospital from December 2020 to December 2021. The drug was prescribed as per recommended indications at a dose of 5 mg twice daily. Age, sex, duration of disease, and prior treatment received were noted. Baseline and 6-month data on the tender joint count, swollen joint count, patient global assessment, and physician global assessment were obtained from the records. Similarly, baseline and 6-month laboratory parameters (CBC, Erythrocyte sedimentation rate, C-reactive protein, LFT, and KFT) were also retrieved. Disease activity was assessed using SDAI at baseline and after 6 months. Adverse effects documented in the records were carefully noted. Results: Seventy-five patients had been commenced on tofacitinib between December 2020 and December 2021. Five patients were lost to follow-up. Twelve patients had stopped the drug after 2–3 months because of inefficacy while 7 had stopped the drug because of adverse effects. Thus, 51 patients (out of 75) had taken tofacitinib for 6 months or more. Of these, 39 achieved EULAR good response (low-disease activity-23, remission-16) and 12 achieved EULAR moderate response. Adverse effects occurred in 27 (36%) patients and included weight gain (8%), cytopenia (6.6%), folliculitis (4%), and alopecia (4%). Others included anxiety, dyspepsia, constipation, chest pain, dyslipidemia, herpes zoster, hypertension, oral thrush, sensory neuropathy, somnolence, and urinary tract infection. Conclusion: Tofacitinib treatment resulted in remission in 16/75 (21%) and LDA in 23/75 (31%) in RA patients who were inadequate responders to conventional synthetic disease-modifying antirheumatic drugs/biological drugs. Adverse effects occurred in 36%.

Long-term safety and efficacy of risankizumab for the treatment of moderate-to-severe plaque psoriasis: Interim analysis of the LIMMitless open-label extension trial up to 5 years of follow-up

Psoriasis is a chronic, inflammatory skin disease often requiring long-term therapy. To evaluate the long-term safety and efficacy of risankizumab in patients with psoriasis. LIMMitless is an ongoing phase 3, open-label extension study evaluating the long-term safety and efficacy of continuous risankizumab 150mg every 12weeks for adults with moderate-to-severe plaque psoriasis following multiple phase 2/3 base studies. This interim analysis assessed safety (ie, monitored treatment-emergent adverse events [TEAEs]) through 304weeks. Efficacy assessments included determining the proportion of patients who achieved ≥90% or 100% improvement in Psoriasis Area and Severity Index (PASI 90/100), static Physician's Global Assessment of clear/almost clear (sPGA 0/1), and Dermatology Life Quality Index of no effect on patient's life (DLQI 0/1) through 256weeks. Among 897 patients randomized to risankizumab in the base studies, 706 were still ongoing at data cutoff. Rates of TEAEs, TEAEs leading to discontinuation, and TEAEs of safety interest were low. At week 256, 85.1%/52.3% of patients achieved PASI 90/100, respectively, 85.8% achieved sPGA 0/1, and 76.4% achieved DLQI 0/1. Open-label study with no placebo or active-comparator group. Long-term continuous risankizumab treatment for up to 5years was well tolerated and demonstrated high and durable efficacy.

Magnetic resonance imaging RAMRIS-SAFE score-A low-risk effective measure of rapid response to therapy in rheumatoid arthritis clinical trials.

To assess the rapidity of magnetic resonance imaging (MRI) measured synovitis (as measured by synovial thickening using the RAMRIS-SAFE score) and bone edema in active rheumatoid arthritis (RA) subjects treated with golimumab. Secondary aims: to correlate MRI measures with disabilities of the arm, shoulder, and hand (DASH), physician global (PhysG) and patient global (PatG) assessments. Patients with active RA and inadequate response to methotrexate were recruited. Active RA was defined as RA with a Disease Activity Score of 28 joints - C-reactive protein ≥4.2 at screening AND active disease (synovitis and edema) of the chosen hand or wrist on MRI at screening, as determined by the central blinded MRI reader (PB). Outcomes measures were assessed at baseline, 2, 6, and 12 weeks. MRI results were interpreted by one experienced observer (PB), blinded to clinical measures. Pearson's correlation co-efficient (SPSS) was used to express the relationship between DASH, PhysG, PatG and MRI measures. Eighteen patients were included in the study. All subjects completed follow-up visits and MRI assessment. Mean age was 60.6 years (range 22-72), and 10 were female, 8 male, and disease duration was mean 4.72 years (range 1-28); all patients were taking background methotrexate. The changes in MRI synovial volume were evident by visit 2. The strongest correlations with the DASH for MRI parameters were total synovial thickening (0.923) and edema (0.921). Golimumab was associated with rapid improvement in clinical measures and patient-reported outcome measures. Mean synovial thickening demonstrated early rapid improvement. MRI synovial thickening demonstrated a strong correlation with DASH, PatG and PhysG.

Application of SLE-DAS to assess subcutaneous belimumab efficacy in a cohort of systemic lupus erythematosus patients.

To assess the efficacy of subcutaneous (sc) belimumab (BLM) by the application of SLE-DAS in a monocentric SLE cohort. We evaluated SLE patients treated with sc BLM from March 2019. Disease activity has been assessed by SLEDAI-2k, SLE-DAS and PGA (Physician Global Assessment) in all the established time-points [baseline (T0), after 1 (T1), 3 (T3), 6 (T6) and 12 (T12) months]. Furthermore, we applied and compared the achievement of remission according to SLE-DAS values (SLEDAS ≤2.08 + PDN ≤5mg/daily) and DORIS definition (clinical SLEDAI- 2k=0 + PGA<0.5 + antimalarial treatment, PDN≤5mg/daily, stable immunosuppressive treatment). We enrolled 86 patients [M/F 5/81, median age 48 years (IQR 17.5), median disease duration 166 months (IQR 216)]. At baseline, median values of SLEDA-2k and SLE-DAS were 6 (IQR 4) and 5.77 (IQR 4.33), respectively, and they significantly correlated (r=0.719, CI 95% 0.586-0.815, p<0.0001). Median duration of treatment was 14 months (IQR 20). We found a significant reduction of SLEDAI-2k and SLE-DAS already at T1, maintained in the subsequent time-points (p<0.0001). At T12, a remission state was achieved by 60.4% of patients according to SLE-DAS definition and by 62.3% according to the DORIS definition. Both definitions of remission have demonstrated an agreement of 84%, with a Cohen's kappa equal to 0.6. In this study we applied SLE-DAS to assess the efficacy of sc BLM, by analysing its over-time changes and by comparing its performance with SLEDAI-2k. Indeed, our results suggest the usefulness of this new activity index in a real-life setting.