Missed opportunities for treatment of inflammatory arthritis and factors associated with non-treatment: An observational cohort study in United States Veterans with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.

OBJECTIVE: To identify factors associated with non-treatment with biologic and non-biologic disease modifying anti-rheumatic drugs (DMARDs) during the 12 months after initial inflammatory arthritis (IA) diagnosis. METHODS: We identified Veterans with incident IA diagnosed in 2007-2019. We assessed time to treatment with Kaplan-Meier curves. We identified associations between non-treatment and factors relating to patients, providers, and the health system with multivariate Generalized Estimation Equation (GEE) log-Poisson. Subgroup analyses included IA subtypes (rheumatoid arthritis [RA], psoriatic arthritis [PsA], and ankylosing spondylitis [AS]) and timeframes of the initial IA diagnosis (2007-11, 2012-15, and 2016-19). RESULTS: Of 18,318 study patients, 40.7 % did not receive treatment within 12 months after diagnosis. In all patients, factors associated with non-treatment included Black race (hazard ratio, 95 % confidence interval: 1.13, 1.08-1.19), Hispanic ethnicity (1.14, 1.07-1.22), Charlson Comorbidity Index ≥2, (1.15, 1.11-1.20), and opiate use (1.09, 1.05-1.13). Factors associated with higher frequency of DMARD treatment included married status (0.86, 0.81-0.91); erosion in joint imaging report (HR: 0.86, 0.81-0.91); female diagnosing provider (0.90, CI: 0.85-0.96), gender concordance between patient and provider (0.91, CI: 0.86-0.97), and diagnosing provider specialty of rheumatology (0.53, CI: 0.49-0.56). CONCLUSION: A high proportion of Veterans with IA were not treated with a biologic or non-biologic DMARD within one year after their initial diagnosis. A wide range of factors were associated with non-treatment of IA that may represent missed opportunities for improving the quality of care through early initiation of DMARDs.

Inhibition of the JAK-STAT Pathway in the Treatment of Psoriasis: A Review of the Literature.

Psoriasis is a highly prevalent dermatological disease associated with an increased systemic inflammatory response. In addition, joint involvement is also present in around 20% of patients. Therefore, treatment modalities used in this condition should be simultaneously effective at improving skin manifestations, reducing inflammation, and addressing psoriatic arthritis when present. Twenty years ago, the introduction of biologic treatments for psoriasis was a turning point in the management of this condition, offering an effective and reasonably safe option for patients whose disease could not be adequately controlled with conventional therapies. At the moment, Janus Kinase inhibitors (JAKis) are a new class of promising molecules in the management of psoriasis. They are orally administered and can show benefits in patients who failed biologic therapy. We conducted a scoping review in order to identify randomized-controlled trials that investigated different JAKis in patients with plaque psoriasis and psoriatic arthritis, with an emphasis on molecules that have been approved by the European Medicines Agency and the Food and Drug Administration. The added value of this study is that it collected information about JAKis approved for two different indications, plaque psoriasis and psoriatic arthritis, in order to provide an integrated understanding of the range of effects that JAKis have on the whole spectrum of psoriasis manifestations.

Prognostic models of drug-induced neutralizing antibody formation in patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis treated with TNF-α blockersockers.

AIM: This study aimed to construct prognostic mathematical models utilizing multifactorial regression analysis to assess the risk of developing drug-induced neutralizing antibodies in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis treated with tumor necrosis factor alpha blockers.

Safety and Efficacy of Golimumab in Indian Patients with Active Spondyloarthritis of Ankylosing Spondylitis or Psoriatic Arthritis: A Multicenter, Noncomparative, Open-Label, Real-World Study.

BACKGROUND: The safety and efficacy of tumor necrosis factor-α (TNF-α) inhibitor therapy for most common rheumatological diseases, ankylosing spondylitis (AS), and psoriatic arthritis (PsA) in controlled clinical trials is well-studied. This study evaluated subcutaneous (SC) golimumab in Indian patients with active spondyloarthritis (SpA) of AS or PsA in a real-world setting. MATERIALS AND METHODS: This phase 4, multicenter, prospective, non-comparative, interventional, 24-week study was performed in patients (age ≥18 years) with active SpA of AS or PsA (NCT03733925). Golimumab 50 mg was given subcutaneously to the patients every 4 weeks. Safety was assessed. The proportion of patients with AS and PsA achieving ≥20% improvement in the Assessment of SpA International Society 20 (ASAS20) criteria and American College of Rheumatology 20 (ACR20) responses, respectively, at weeks 14 and 24 were efficacy endpoints. RESULTS: Of the 100 patients enrolled (men: 78 [78.0%]; mean age: 36.7 [12.02] years), 94 (94.0%) patients completed the study. Treatment-emergent adverse events with golimumab were observed in 29/100 (29.0%) patients, and nasopharyngitis and upper respiratory tract infection (5.0% each) were the most common (≥5%). Deaths were not reported. At week 14, 74.5% (95% confidence interval [CI]: 59.7; 86.1%) of patients with AS and 84.6% (95% CI: 69.5; 94.1%) of patients with PsA achieved ASAS20 and ACR20 responses, which were sustained at week 24 (ASAS20: 66.0% [95% CI: 50.7, 79.1%]; ACR20: 93.2% [95% CI: 81.3, 98.6%]), respectively. CONCLUSION: Golimumab (50 mg) administered subcutaneously was safe and effective in Indian patients with active SpA of AS or PsA during the 24-week study period with no new safety signals.

Choosing the right biologic treatment for moderate-to-severe plaque psoriasis: the impact of comorbidities.

INTRODUCTION: Psoriasis is a chronic inflammatory skin disease often associated with several comorbidities, such as psoriatic arthritis, inflammatory bowel disease, obesity, diabetes mellitus or cardiovascular diseases, infections, or cancer, among others. With the progressive aging of the population, a growing number of patients with psoriasis can be expected to present multiple comorbidities. Currently, there is a wide range of biological treatments available for moderate to severe psoriasis, including tumor necrosis alpha (TNF) inhibitors, IL12/23 inhibitor, IL17 inhibitors, and IL23 inhibitors. AREAS COVERED: This review aims to describe the specific characteristics of these drugs in relation to psoriasis comorbidities, in order to facilitate decision-making in clinical practice. EXPERT OPINION: Some of the biological treatments can influence comorbidities, in some cases even improving them. Therefore, comorbidities are a key factor when deciding on one biological treatment over another. The development of new drugs is expanding the therapeutic arsenal for psoriasis. A high level of expertise in the field with a detailed knowledge of the characteristics of every drug is imperative to provide personalized medicine.

Efficacy of risankizumab across subgroups in patients with active psoriatic arthritis: a post hoc integrated analysis of the phase 3 KEEPsAKE 1 and KEEPsAKE 2 randomized controlled trials.

In the KEEPsAKE 1 (NCT03675308) and KEEPsAKE 2 (NCT03671148) phase 3 trials, risankizumab demonstrated greater efficacy compared with placebo in patients with active psoriatic arthritis (PsA). This post hoc integrated analysis evaluated achieving the following efficacy outcomes at weeks 24 and 52 by baseline demographics and clinical characteristics: ≥20%/50%/70% improvement in American College of Rheumatology response criteria (ACR20/50/70), ≥90% improvement in Psoriasis Area and Severity Index, minimal disease activity status, Low Disease Activity status (Disease Activity in Psoriatic Arthritis), and minimal clinically important difference in pain. Baseline demographics and clinical characteristics were similar between risankizumab (n = 707) and placebo (n = 700) groups. Numerically higher ACR20 response rates at week 24 (primary endpoint) were observed among the risankizumab (46.3%-60.1%) vs. placebo (15.5%-36.2%) cohorts, regardless of subgroups. At week 52, consistent proportions of patients randomized to risankizumab achieved ACR20 (48.6%-75.8%) while those initially randomized to placebo and switched to risankizumab experienced an improvement from week 24 (43.7%-63.9%), regardless of subgroups. Similar trends were observed for other efficacy measures assessing rigorous skin response criteria, composite measures of overall disease activity, and PsA-related symptoms. Risankizumab treatment was efficacious among patients with varying demographic and psoriatic disease characteristics through 52 weeks.

Real-world outcomes and drug survival of brodalumab: results from the German Psoriasis Registry PsoBest.

Brodalumab, a human monoclonal antibody that targets interleukin-17 receptor A (IL-17RA), is approved in the US and EU for treatment of adults with moderate-to-severe plaque psoriasis. Although brodalumab has demonstrated efficacy and safety vs placebo in clinical trials of patients with psoriasis and psoriatic arthritis (PsA), real-world evidence is needed to evaluate long-term effectiveness and safety of brodalumab in routine care. This interim analysis of the German Psoriasis Registry PsoBest examined patient profiles, treatment outcomes, and drug survival of first-time use of brodalumab for 12 months in adult patients with moderate-to-severe plaque-type psoriasis (with and without PsA) (data cutoff: June 30, 2021). Clinician and patient-reported outcomes of the total cohort (n = 227; PsA, n = 38) indicated a rapid response to brodalumab treatment within the first 3 months, which was maintained up to 12 months. The overall one-year drug survival rate was 76.2%, the mean time to discontinuation was 8.3 months. Reasons for discontinuation were mainly loss/lack of effectiveness, followed by adverse events, contraindication and skin clearance. In sum, brodalumab demonstrated rapid and sustained effectiveness and was well-tolerated over 12 months in German patients with moderate-to-severe psoriasis and PsA in a real-world setting.

Psoriatic arthropathy in patients with previous neoplasia: a case series of four patients treated with secukinumab and literature review.

OBJECTIVE: Psoriasis and psoriatic arthritis (PsA) are closely linked to cancer, as supported by the literature. Systemic treatments for psoriasis and PsA, namely non-biological disease-modifying anti-rheumatic drugs (DMARDs), have been associated with increased cancer risk in both conditions. New, more effective biological DMARDs (bDMARDs) do not seem to be associated with higher overall cancer risk compared to those not receiving bDMARDs, opening up possibilities for treating patients with previous or ongoing oncological disease alongside psoriasis and PsA. However, limited literature exists on treating PsA patients with cancer with bDMARDs. This study aims to assess the safety of secukinumab, a bDMARD, in patients with PsA and concurrent cancer. Here, we describe a case series of four patients with PsA treated with bDMARD secukinumab and review the literature on the subject. CASE SERIES: We assessed the laboratory parameters and clinical characteristics of 4 patients with PsA treated with the bDMARD secukinumab and followed up until 30 months. Three patients had oncological disease in remission, while one had active neoplasia. No cancer progression was observed during the treatment of these patients with secukinumab. CONCLUSIONS: In conclusion, our case series, consisting of four PsA patients with concurrent neoplasia treated with secukinumab, showed no evidence of cancer progression and represents the first case of PsA described in the literature treated during active oncological disease, lending support to the safety of secukinumab for the treatment of patients with PsA and concomitant neoplasia.

[Faecal microbiota study reveals specific dysbiosis in spondyloarthritis according to subtype, disease activity and treatment]. / Estudio de microbiota fecal revela disbiosis específica en espondiloartritis, según subtipo, actividad de la enfermedad y tratamiento.

OBJECTIVE: To compare the diversity and composition of the gastrointestinal microbiome of patients with SpA. METHODS: MiSeq sequencing of the V3-V4 region of the 16S ribosomal RNA gene was performed on DNA isolated from stool. Patients with concurrent SpA and IBD were excluded. Differences were assessed for richness and diversity indices by QIIME 2™. Differences between means >0,2% with a p-value<0,05 were assumed significant. Institutional Ethics Committee endorsement. RESULTS: 69 individuals included, 49 with SpA (ankylosing spondylitis-AS 72,9%, psoriatic arthritis-PsA 18,8%, reactive arthritis-ReA 8,3%) 5 positive controls-dysbiosis and 15 controls-eubiosis. Conventional treatment in 42,9%, anti-IL-17 16,3% and anti-TNF 40,8%. By subtype, statistically significant differences in favour of AS were found for the diversity indices. AS vs PsA there was a difference in favour of AS for Clostridium clostridioforme (p=0,002), Gemmiger formicilis (p=0,009), Roseburia inulivorans (p=0,008) and Lachnospira pectinoschiza. AS vs ReA there was a difference in favour of AS for L. pectinoschiza (p=0,009), Ruminococcus callidus (p=0.006), Clostridium ruminantium (p=0.031); G. formicilis (p=0,034). Diversity and richness showed differences in patients with high activity for Simpson's and Pielou's indices. In high activity, lower enrichment of Bacteroides eggerthii (p= 0,0003), C. ruminantium (p= 0,026) and Alistipes putredinis (p=0,035) was found. The number of ASV was higher in the anti-IL-17 vs conventional group (p=0.025) and a trend between anti-IL-17 vs anti-TNF (p=0.09). In anti-TNF there was a lower proportion for C. clostridioforme (p=0.023), G. formicilis (p=0.030) and R. callidus (p= 0.003). In anti IL-17, Alistipes indistinctus (p= 0.012) was decreased. CONCLUSIONS: There are differences in microbial diversity for SpA subtypes. The level of disease activity is plausible to influence the composition of the faecal microbiota. Anti-TNFα treatment may influence the microbiome environment favouring restoration of the gut microbiota, while anti-IL-17 may maintain an inflammatory environment.

OBJETIVO: Comparar la diversidad y composición del microbioma gastrointestinal de pacientes con EspA. MÉTODOS: La secuenciación MiSeq de la región V3-V4 del gen ARN ribosomal 16, se realizó en ADN aislado de heces. Se excluyeron pacientes con EspA y EII simultánea. Se evaluaron diferencias para los índices de riqueza y diversidad por medio de QIIME 2™. Las diferencias entre medias> 0,2%, con un valor de p< 0,05, se asumieron significativas. Aval del Comité de Ética Institucional. RESULTADOS: 69 individuos incluidos, 49 con EspA (espondilitis anquilosante-EA 72,9%, artritis psoriásica-APs 18,8%, artritis reactiva-ARe 8,3%), cinco controles positivos-disbiosis y 15 controles-eubiosis. El tratamiento convencional en 42,9%, anti-IL-17 16,3%, y anti-TNF 40,8%. Por subtipo-EasP, se encontraron diferencias estadísticamente significativas a favor de EA para los índices de diversidad. Entre EA vs APs, hubo diferencia a favor de EA para Clostridium clostridioforme (p=0,002), Gemmiger formicilis (p=0,009), Roseburia inulivorans (p=0,008) y Lachnospira pectinoschiza. Entre EA vs ARe hubo diferencia a favor de EA para L. pectinoschiza (p=0,009), Ruminococcus callidus (p = 0,006), Clostridium ruminantium (p=0,031); G. formicilis (p=0,034). La diversidad y riqueza mostraron diferencias en pacientes con alta actividad para los índices de Simpson y Pielou. En alta actividad, se encontró menor enriquecimiento de Bacteroides eggerthii (p=0,0003), C. ruminantium (p= 0,026) y Alistipes putredinis (p= 0,035). El número de ASV fue superior en el grupo de anti IL-17 vs convencional (p=0.025), y una tendencia entre anti IL-17 vs anti-TNF (p=0,09). En anti TNF hubo menor proporción para C. clostridioforme (p=0,023), G. formicilis (p=0,030) y R. callidus (p= 0,003). Y en anti IL-17, Alistipes indistinctus (p= 0,012), estuvo disminuida. CONCLUSIONES: Existen diferencias en la diversidad microbiana para los subtipos de EspA. El nivel de actividad de la enfermedad es plausible para influir en la composición de microbiota fecal. El tratamiento con anti-TNFα, puede influenciar el ambiente del microbioma favoreciendo la restauración de la microbiota intestinal, mientras los anti IL-17 podrían mantener un ambiente inflamatorio.

Small Spleen Peptides (SSPs) Shape Dendritic Cell Differentiation through Modulation of Extracellular ATP Synthesis Profile.

Restoring peripheral immune tolerance is crucial for addressing autoimmune diseases. An ancient mechanism in maintaining the balance between inflammation and tolerance is the ratio of extracellular ATP (exATP) and adenosine. Our previous research demonstrated the effectiveness of small spleen peptides (SSPs) in inhibiting psoriatic arthritis progression, even in the presence of the pro-inflammatory cytokine TNFα, by transforming dendritic cells (DCs) into tolerogenic cells and fostering regulatory Foxp3+ Treg cells. Here, we identified thymosins as the primary constituents of SSPs, but recombinant thymosin peptides were less efficient in inhibiting arthritis than SSPs. Since Tß4 is an ecto-ATPase-binding protein, we hypothesized that SSPs regulate exATP profiles. Real-time investigation of exATP levels in DCs revealed that tolerogenic stimulation led to robust de novo exATP synthesis followed by significant degradation, while immunogenic stimulation resulted in a less pronounced increase in exATP and less effective degradation. These contrasting exATP profiles were crucial in determining whether DCs entered an inflammatory or tolerogenic state, highlighting the significance of SSPs as natural regulators of peripheral immunological tolerance, with potential therapeutic benefits for autoimmune diseases. Finally, we demonstrated that the tolerogenic phenotype of SSPs is mainly influenced by adenosine receptors, and in vivo administration of SSPs inhibits psoriatic skin inflammation.

Effectiveness of secukinumab in patients with psoriasis and psoriatic arthritis in a Saudi real-world setting.

INTRODUCTION: Psoriasis (PsO) is an immune-mediated chronic inflammatory disease that results in severe outcomes that impact the patient's quality of life and work productivity. We investigated the effectiveness of secukinumab in patients with chronic plaque psoriasis and psoriatic arthritis (PsA) over a 12-month period. METHODS: This was a longitudinal, retrospective study of the medical records of 81 patients with psoriasis and/or psoriatic arthritis who had been treated with secukinumab for at least 12 weeks. RESULTS: The Psoriasis Area Severity Index (PASI), Body Surface Area (BSA) percentage, and Dermatology Quality of Life Index (DLQI) among patients with PsO and PsO-PsA showed a statistically significant decrease from baseline over 12 months by approximately 9.86, 19.3%, and 9.7, respectively (p values < 0.001 for each). Moreover, there was a statistically significant decrease in the overall Disease Activity in Psoriatic Arthritis score (DAPSA) by approximately 22.35 from baseline over 12 months of treatment (p < 0.001). Considering the patients who started secukinumab 12 months or more prior to the study cutoff date, the 12-month retention rate was 85%. CONCLUSION: In a Saudi real-world setting, secukinumab proved to be an efficient medication with high efficacy and retention rates.

IL-23 past, present, and future: a roadmap to advancing IL-23 science and therapy.

Interleukin (IL)-23, an IL-12 cytokine family member, is a hierarchically dominant regulatory cytokine in a cluster of immune-mediated inflammatory diseases (IMIDs), including psoriasis, psoriatic arthritis, and inflammatory bowel disease. We review IL-23 biology, IL-23 signaling in IMIDs, and the effect of IL-23 inhibition in treating these diseases. We propose studies to advance IL-23 biology and unravel differences in response to anti-IL-23 therapy. Experimental evidence generated from these investigations could establish a novel molecular ontology centered around IL-23-driven diseases, improve upon current approaches to treating IMIDs with IL-23 inhibition, and ultimately facilitate optimal identification of patients and, thereby, outcomes.

Early identification of golimumab-treated patients with higher likelihood of long-term retention.

Background: The early identification of patients' profiles most likely to respond to and maintain long-term therapy with a biological drug can have clinical and cost-effectiveness implications. Objectives: To evaluate the utility of an innovative approach for early identification of patient profiles associated with long-term persistence of golimumab, a tumour necrosis factor inhibitor, in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (SpA) under real-world conditions. Design: Retrospective non-interventional database analysis. Methods: Kaplan-Meier curves of golimumab retention over 8 years from the BIOBADASER registry, overall and by indication, were analysed using a novel approach (a two-phase decay model) to identify the point at which the golimumab retention curve shifted from rapid (indicating high golimumab discontinuation rate) to slow decay (low discontinuation rate). Factors associated with golimumab retention at these time points were identified using Cox regression, and retention rates for different patient profiles were calculated. Results: 885 patients were included. The golimumab retention curve shifted from rapid to slow decay at month 10 for the overall population (retention rate: 73.4%), at month 24 for RA patients (retention: 45.0%), and at month 8 for SpA, including axial SpA and PsA (81.6%). Factors associated with golimumab discontinuation at these early points were, overall, similar to those previously identified at year 8 (RA diagnosis, golimumab as second- or third-line of biological therapy, disease activity over the median and treatment with corticosteroids at golimumab initiation, advanced age [in RA], and female gender [in SpA]). Conclusion: With this novel approach, the factors associated with long-term retention were identified in the initial period of rapid discontinuation of golimumab.

The steroid-sparing effect of JAK inhibitors across multiple patient populations.

Introduction: JAK-inhibitors (JAK-i) represent an effective treatment in Rheumatoid Arthritis (RA) and Psoriatic Arthritis (PsA). Oral glucocorticoids (OGC) are commonly used in combination with JAK-i to reach therapeutic target. We aimed to assess, in a real-life setting, the reduction of OGC dose during JAK-i treatment in active RA and PsA patients. Methods: We prospectively enrolled 103 patients (88 RA, 15 PsA) treated with JAK-i: 24% bio-naïve (b-naïve), 76% bDMARD-insufficient responders (bDMARD-IR) and 40% difficult to treat (D2T), defined as failure of ≥2 bDMARDs with different mechanism of action. Disease activity (DAS28 and DAPSA, VAS-pain, GH) and OGC dose was collected at baseline and after 3, 6 and 12 months (T3, T6, T12) of treatment. Results: In all the cohort and in b-naïve patients we reported a reduction of OGC dose at all time-points; bDMARD-IR patients were able to reduce OGC dose at T3 and T12; D2T ones only at T3. We reported an improvement of disease activity and withdrawal of OGC as early as three months of therapy, at all time-points, regardless of line of bDMARD treatment. Conclusion: Chronic OGC may cause detrimental bone, metabolic, cardiovascular side effects and infections; therefore JAK-i steroid-sparing effect may be beneficial for patients in long-term treatment.

Tuberculosis and Nontuberculous Mycobacterial Infections in Patients with Spondyloarthritis: A Population-Based Study.

Background and Objectives: Tuberculosis is caused by Mycobacterium tuberculosis (MTB), while nontuberculous mycobacteria (NTM) encompass a group of mycobacterial species that are distinct from the MTB complex and leprae. Spondyloarthritis (SpA) is a group of chronic inflammatory diseases with shared clinical characteristics and is treated with biological agents; however, their use may elevate the risk of MTB and NTM infections. This study aimed to compare the incidence and risk of MTB and NTM infections in patients with SpA, including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), using a population-based approach. Materials and Methods: This study included 2333 patients with SpA and 9332 age- and sex-matched controls from the Korea National Health Insurance Service-National Sample Cohort database from 2002 to 2019. The patients were identified using the International Classification of Diseases-10 codes for AS, PsA, MTB, and NTM. Results: The results showed that a negligible percentage of patients with SpA developed NTM (0.002%) and MTB (0.016%), with no significant difference in the incidence rate ratio (IRR) compared to controls. Among patients with SpA treated with biologics, the IRRs for NTM and MTB were 5.66 and 3.069, respectively; however, these were not statistically significant. No cases of NTM or MTB infection were reported in female patients with SpA treated with biologics. In both the SpA patient group and the control group, the incidence of MTB was higher in individuals over 60 years old compared to those under 60 years old. Cox proportional hazard analysis revealed a significant adjusted hazard ratio of 1.479 for MTB in patients with SpA after adjusting for age, sex, smoking history, insurance level, and comorbidities. However, this significance was not maintained when biological therapy was further adjusted. Conclusions: Our study indicated that the risks of NTM and MTB infection are not elevated in patients with SpA. Although biological use may potentially increase the risk of MTB infection, it does not lead to a significant increase in incidence rates. Proactive screening for latent tuberculosis and adequate prophylaxis using biologics can effectively manage the risk of NTM and MTB infections.

Construct validity, reliability, and threshold value for treatment goals of the Thai version of the 12-item Psoriatic Arthritis Impact of Disease Questionnaire for patients with psoriatic arthritis.

OBJECTIVE: To determine the construct validity, reliability, and treatment goal threshold of a Thai-language version of the 12-item Psoriatic Arthritis Impact of Disease (Thai-PsAID) questionnaire in patients with psoriatic arthritis (PsA). METHODS: This cross-sectional study involved administering the proposed Thai-PsAID to 117 Thai patients with PsA. Reliability was assessed by Cronbach's α test and intraclass correlation coefficient (ICC). Construct validity was assessed using Spearman correlation with clinical disease activity index for psoriatic arthritis (cDAPSA), the Health Assessment Questionnaire (HAQ), EQ-5D index, and the patient-acceptable symptom state (PASS). The optimal cutoff score of the Thai-PsAID for minimal disease activity (MDA) was determined by receiver operating characteristic curves. RESULTS: Participants had a mean age of 49.5 years, 61 (52.1%) were female, and the median disease duration was 5 years. The median Thai-PsAID score was 2.1, with a Cronbach's α coefficient of .95 and an ICC of 0.77. The mean time to complete the Thai-PsAID was 2.1 min, with no missing data. The Thai-PsAID score demonstrated a moderate correlation with the cDAPSA, HAQ, and EQ-5D with indices (Spearman's rho of .64, .54, and -.55, respectively). The cutoff of 2.7 has 81%-84% sensitivity and 69%-85% specificity for classifying patients with MDA, satisfied PASS, and indicating no need to escalate medication. CONCLUSIONS: The Thai-PsAID is a valid, reliable, and feasible tool for measuring PsA prognosis. A cutoff of 2.7 accurately discriminates MDA and PASS and indicates no need for medication escalation. The Thai-PsAID may be used as a standalone measure.

Real-world evaluation of persistence, effectiveness and usage patterns of tofacitinib in treatment of psoriatic arthritis in Australia.

OBJECTIVES: To describe treatment patterns and persistence of tofacitinib, interleukin 17 inhibitors (IL-17Ai) and tumour necrosis factor inhibitors (TNFi), in patients with psoriatic arthritis (PsA). METHODS: Data from adult patients with PsA and who had received at least one prescription of tofacitinib, IL-17Ai or TNFi between May 2019 and September 2021 were sourced from the Australian OPAL dataset. Persistence, analysed via Kaplan-Meier methods, and propensity score matching between tofacitinib and bDMARD (IL-17Ai and TNFi) groups were conducted. RESULTS: Of 16,692 patients with PsA, 1486 (n = 406 tofacitinib, n = 416 IL-17Ai and n = 664 TNFi) were included. More females were in the tofacitinib group (75.4%) than in the IL-17Ai (61.1%) and TNFi (64.8%) groups. Overall, 19.2% of tofacitinib patients were first line, compared with 41.8% of IL-17Ai and 62.8% of TNFi patients. In the overall population, the median persistence was 16.5 months (95% CI 13.8 to 19.5 months), 17.7 months (95% CI 15.8 to 19.6 months) and 17.2 months (95% CI 14.9 to 20.5 months) in the tofacitinib, IL-17Ai and TNFi groups, respectively. Persistence was similar in the tofacitinib/IL-17Ai matched population; however, in the tofacitinib/TNFi matched population, persistence was longer in the tofacitinib group (18.7 months, 95% CI 15.6 to 21.4 months) compared with the TNFi group (12.2 months, 95% CI 19.9 to 14.9 months). CONCLUSIONS: In this Australian real-world dataset, tofacitinib was more frequently used in later lines and among a slightly higher proportion of female patients than IL-17Ai or TNFi. Overall, treatment persistence was similar for tofacitinib, IL-17Ai and TNFi, but tofacitinib exhibited longer persistence than TNFi in a matched population. Key Points • This is the first, large real-world study from Australia investigating the demographics, treatment patterns and comparative treatment persistence of patients with psoriatic arthritis (PsA) treated with tofacitinib and biologic disease-modifying drugs (bDMARDs). • The study suggests that tofacitinib is an effective intervention in PsA with at least comparable persistence to bDMARDs: tumour necrosis factor inhibitors (TNFi) and interleukin-17 A inhibitors (IL-17Ai).

Association between enthesitis/dactylitis resolution and patient-reported outcomes in guselkumab-treated patients with psoriatic arthritis.

OBJECTIVES: To evaluate the association between enthesitis resolution (ER) and dactylitis resolution (DR) and meaningful improvements in patient-reported outcomes (PROs) among biologic-naïve patients with PsA receiving guselkumab in the DISCOVER-2 study. METHODS: Enthesitis and dactylitis, characteristic lesions of PsA, were evaluated by independent assessors using the Leeds Enthesitis Index (range, 0-6) and Dactylitis Severity Score (range, 0-60). Proportions of patients with ER or DR (score = 0) among those with score > 0 at baseline were determined at weeks 24, 52, and 100. PROs included: fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue]), pain (0-100 visual analog scale), physical function (Health Assessment Questionnaire-Disability Index [HAQ-DI]), and health-related quality of life (36-item Short-Form Health Survey physical/mental component summary [SF-36 PCS/MCS]). Meaningful responses were defined as: improvements of ≥ 4 for FACIT-Fatigue, ≥ 0.35 for HAQ-DI, and ≥ 5 for SF-36 PCS/MCS and absolute scores of ≤ 15 for minimal pain and ≤ 0.5 for normalized HAQ-DI. Associations between ER/DR status and PRO response status were tested using a Chi-square test. RESULTS: Guselkumab-treated patients with ER were more likely than those without ER to achieve minimal pain (p < 0.001), normalized HAQ-DI (p < 0.001), and PCS response (p < 0.05) at weeks 24, 52, and 100. Patients with DR were more likely than those without DR to achieve FACIT-Fatigue response at week 24 and week 52 (both p ≤ 0.01) and minimal pain at week 24 and normalized HAQ-DI at week 52 (both p ≤ 0.03). CONCLUSION: In biologic-naïve patients with active PsA treated with guselkumab, achieving ER or DR was associated with durable improvements in selected PROs, including those of high importance to patients. TRIAL REGISTRATION: ClinicalTrials.gov ( https://clinicaltrials.gov ) NCT03158285; Registered: May 16, 2017. Key Points • At week 100, 65% and 76% of guselkumab-treated patients achieved enthesitis and dactylitis resolution (ER/DR). • Achieving ER was associated with achieving DR and vice versa through the end of study. • Achieving ER or DR was associated with durable and meaningful improvements in selected patient-reported outcomes.

Efficacy and safety of tofacitinib for chronic plaque psoriasis and psoriatic arthritis: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: To summarize and analyze the results of published randomized controlled trials of tofacitinib for the treatment of chronic plaque psoriasis and psoriatic arthritis(PsA) and discuss its efficacy and safety. PATIENTS AND METHODS: An exhaustive systematic search encompassing PubMed, Cochrane, Embase, and Web of Science databases was conducted up to July 2023. Studies eligible for inclusion were analyzed, organized using Review Manager version 5.4.1 (Cochrane Collaboration, Oxford, UK) and STATA 15.0 version (Stata Corp, College Station, TX, USA) software. RESULTS: A total of six articles, covering 1393 patients (844 treated with tofacitinib and 549 with placebo), were included. The foundational characteristics of tofacitinib and placebo group showed similarity, except for age and Dermatology Life Quality Index (DLQI) score, especially in the context of chronic plaque psoriasis. It is noteworthy that we discovered tofacitinib exhibited a significant impact on Psoriasis Area and Severity Index 75 (PASI75) response, Physician's Global Assessment (PGA) response, and adverse events (AEs) in cases of chronic plaque psoriasis. Similarly, tofacitinib demonstrated substantial influence on American College of Rheumatology 20/50 (ACR20/50) response, PASI75 response, as well as alterations in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score, Health Assessment Questionnaire-Disability Index (HAQ-DI) Score, Dactylitis Severity Score (DSS), and Leeds Enthesitis Index (LEI) Score in the context of psoriatic arthritis (PsA). Nevertheless, there was no statistically significant impact of tofacitinib on serious adverse events (SAEs) in chronic plaque psoriasis, as well as on both adverse events (AEs) and SAEs in psoriatic arthritis (PsA). CONCLUSIONS: A comprehensive analysis revealed that tofacitinib has a positive effect on addressing skin and joint symptoms, as well as improving the quality of life for patients with chronic plaque psoriasis and psoriatic arthritis (PsA). However, the safety of the drug's long-term usage even requires further validation. Key Points • In 6 analyses involving a total of 1393 patients, tofacitinib exhibits positive effect on the treatment of both chronic plaque psoriasis and psoriatic arthritis (PsA). • Although dose-based subgroup analyses have demonstrated effectiveness. Some studies indicate that the 5-mg dose (twice daily) may not show an effect due to the failure of non-inferiority trials comparing tofacitinib with placebo. Therefore, caution is required when interpreting its effectiveness. On the other hand, the 10-mg dose (BID) has been associated with an increase in adverse events and serious adverse events, and is recommended to be used with caution in patients with cardiovascular or uveitis risk factors. • Tofacitinib has efficacy in comorbid psychiatric disorders (depression, anxiety, or Alzheimer's disease) and inflammatory bowel disease (ulcerative colitis), but patients with comorbid renal insufficiency, hepatic dysfunction, osteoporosis, cardiovascular disease, or uveitis may need to be moderated or avoided with tofacitinib.

Evaluation of diagnostic and therapeutic delay in patients with rheumatoid arthritis and psoriatic arthritis.

OBJECTIVE: A monocentric cross-sectional study recruiting rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients residing in the Lazio region, Italy, to assess factors related to diagnostic delay and treatment accessibility. METHODS: Clinical/serological data, including the time between symptom onset, diagnosis, and the beginning of treatment, were collected. Residence, referral to a rheumatologic center, physician who made the diagnosis, and previous misdiagnosis were also evaluated. RESULTS: A higher diagnostic delay (p=0.003), and time between symptom onset and the start of I-line therapy (p=0.006) were observed in PsA compared to RA. A delayed start of II-line therapy was observed in RA compared to PsA (p=0.0007). Higher diagnostic delay (p=0.02), and time between symptom onset and the start of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) (p=0.02) were observed among residents of small-medium cities for both groups. Patients who have been diagnosed by another physician rather than a rheumatologist had a longer diagnostic delay (p=0.034) and a delayed start of I-line therapy (p=0.019). Patients who received a different previous diagnosis experienced greater diagnostic delay (p=0.03 and p=0.003) and time of start of csDMARDs (p=0.05 and p=0.01) compared with those receiving RA or PsA as the first diagnosis. PsA had a delay in starting targeted synthetic disease-modifying anti-rheumatic drugs (p=0.0004) compared to RA. Seronegative RA had delayed diagnosis (p=0.02) and beginning of therapies (p=0.03; p=0.04) compared to seropositive ones. CONCLUSIONS: According to our results, greater diagnostic delay was found in PsA compared to RA, in patients living in small-medium cities, in those who did not receive the diagnosis from a rheumatologist, in those who were previously misdiagnosed, and in seronegative RA.