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.

Use of risk chart algorithms for the identification of psoriatic arthritis patients at high risk for cardiovascular disease: findings derived from the project CARMA cohort after a 7.5-year follow-up period.

OBJECTIVE: To assess the predictive value of four cardiovascular (CV) risk algorithms for identifying high-risk psoriatic arthritis (PsA) patients. METHODS: Evaluation of patients with PsA enrolled in the Spanish prospective project CARdiovascular in RheuMAtology. Baseline data of 669 PsA patients with no history of CV events at the baseline visit, who were followed in rheumatology outpatient clinics at tertiary centres for 7.5 years, were retrospectively analysed to test the performance of the Systematic Coronary Risk Assessment (SCORE), the modified version (mSCORE) European Alliance of Rheumatology Associations (EULAR) 2015/2016, the SCORE2 algorithm (the updated and improved version of SCORE) and the QRESEARCH risk estimator version 3 (QRISK3). RESULTS: Over 4790 years of follow-up, there were 34 CV events, resulting in a linearised rate of 7.10 per 1000 person-years (95% CI 4.92 to 9.92). The four CV risk scales showed strong correlations and all showed significant associations with CV events (p<0.001). SCORE, mSCORE EULAR 2015/2016 and QRISK3 effectively differentiated between low and high CV risk patients, although the cumulative rate of CV events observed over 7.5 years was lower than expected based on the frequency predicted by these risk scales. Additionally, model improvement was observed when combining QRISK3 with any other scale, particularly the combination of QRISK3 and SCORE2, which yielded the lowest Akaike information criterion (411.15) and Bayesian information criterion (420.10), making it the best predictive model. CONCLUSIONS: Risk chart algorithms are very useful for discriminating PsA at low and high CV risk. An integrated model featuring QRISK3 and SCORE2 yielded the optimal synergy of QRISK3's discrimination ability and SCORE2's calibration accuracy.

Non-Pharmacological Interventions for Treating Psoriatic Arthritis.

Background and Objective: In this review, we discuss evidence concerning the management of psoriatic arthritis (PsA) patients with non-pharmacological interventions and additionally develop physical training protocols that could be prescribed to these patients. Methods: We selected 110 articles, published on PubMed and Google Scholar databases from 1972 to date, investigating the effects of generic hygienic-dietary recommendations and training programs in PsA or psoriasis (PSO) individuals. Results: Although data in support are limited, aerobic, endurance, and strength exercises as well as complementary techniques may all be useful in preserving or improving residual functional capacity, joint flexibility, and muscle strength. Exercise may reduce systemic inflammation, pain, and fatigue and additionally control PsA comorbidities, like dysmetabolism or obesity. Conclusions: The polyhedral clinical expression of PsA underlines the need for a multidisciplinary approach combining the synergistic effects of pharmacological and non-pharmacological treatments. The latter range from preventive measures, like dietary modifications, weight loss, and cigarette smoking cessation, to personalized training protocols according to disease activity and phenotype, comorbidities, and individual tolerability. In these patients, we strongly encourage the regular practice of motor activity at progressively increasing intensity with combined supervised aerobic, strength, endurance, and stretching exercises.

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.

Risk of developing psoriatic arthritis in psoriasis cohorts with arthralgia: exploring the subclinical psoriatic arthritis stage.

OBJECTIVE: Subjects with subclinical psoriatic arthritis (PsA), defined as the presence of arthralgia in psoriasis (PsO), are at higher risk of PsA but scant real-world data exist. Our aims were to (1) estimate the probability of PsA development in subclinical PsA, (2) characterise subclinical PsA symptoms and (3) determine the clinical patterns at PsA diagnosis. METHODS: Patients with PsO, mainly subclinical PsA, were evaluated longitudinally in two European cohorts. The key outcome was new-onset PsA. Musculoskeletal symptoms including inflammatory and non-inflammatory symptoms before PsA diagnosis were collected. Occurrence of PsA was analysed with survival analysis and cumulative incidence functions (CIFs). RESULTS: 384 patients with PsO were included with a mean follow-up of 33.0 (±20.9) months. 311 of 384 (80.9%) had subclinical PsA with a PsA incidence rate of 7.7 per 100 patient-years. Subclinical PsA displayed a higher risk of PsA development compared with PsO (HR=11.7 (95% CI 1.57 to 86.7), p=0.016). The probability of new-onset PsA estimated by the CIF was 9.4% (95% CI 4.7% to 10.6%) at month 12 and 22.7% (95% CI 17.2% to 28.6%) at month 36. 58.9% of cases reported inflammatory symptoms in the months immediately prior to PsA diagnosis but prior non-inflammatory symptoms were evident in 83.9% prior to PsA diagnosis. Peripheral joint swelling was the predominant PsA presentation pattern (82.1%). CONCLUSIONS: The probability of PsA development among subclinical PsA was relatively high, emphasising the importance of emergent musculoskeletal symptoms when aiming for PsA prevention. Joint swelling was the dominant feature in new-onset PsA, likely reflecting clinical confidence in recognising joint swelling.

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.

Ultrasonographic and power doppler parameters of nails fail to differentiate between onychodystrophy in patients with psoriasis vulgaris or psoriatic arthritis.

BACKGROUND: Nail involvement is frequent in patients with psoriasis (Pso) and psoriatic arthritis (PsA) and there is a relationship between nail involvement and inflammation of the enthesis. The main objective of the present study is to describe the ultrasound findings and clinical characteristics of nails from patients with psoriasis and psoriatic arthritis with and without nail dystrophy. METHODS: A cross-sectional study including consecutive patients with PsO and PsA was carried out. The study patients were divided into 4 groups, totaling 120 participants. Group 1: patients with psoriasis vulgaris and clinically normal nails; Group 2: patients with psoriasis vulgaris and onychodystrophy; Group 3: patients with psoriatic arthritis and clinically normal nails; Group 4: patients with psoriatic arthritis and onychodystrophy; All patients were submitted to dermatological and rheumatological clinical analysis. Ultrasound examinations was performed by a single examiner, blinded to all clinical data, with ultrasound high resolution, in B-mode or gray-scale (GS), Power Doppler (PD) and Spectral Doppler. RESULTS: A significant difference was found between the groups regarding the variable Psoriasis Area and Severity Index (PASI) (p = 0.008) and body surface area (BSA) (p = 0.005), with patients with psoriatic arthritis having lower PASI and BSA compared to patients with only cutaneous psoriasis. A positive relationship was found with the average ultrasound thickness of the nail bed and the Nail Psoriasis Severity Index (NAPSI) in correlation analysis (rho = 0.344). When we grouped patients with psoriasis and psoriatic arthritis, there was no significant difference between the cutaneous psoriasis groups and the psoriatic arthritis groups in terms of nail plate GS (p = 0.442), nail bed PD (p = 0.124). CONCLUSION: Greater nail bed thickness indicates early psoriatic nail disease, as confirmed in our study correlating NAPSI with nail bed thickness. Ultrasonography is a low-cost exam, promising in the evaluation, showing that the ultrasound grayscale is consistent with those who have dystrophic nails, but it can't distinguish psoriasis from psoriatic arthritis, even in those with nail dystrophy.

[HLA alleles heterogeneity in a sample of colombian patients with a diagnosis of psoriatic arthritis]. / Heterogeneidad de alelos HLA, en una muestra de pacientes con diagnóstico de artritis psoriásica en Colombia.

OBJECTIVE: The objective is to describe the HLA allelic frequency in PsA and correlate it with demographic and clinical variables. METHODS: Retrospective study of adult patients with a diagnosis of PsA (n=23) and healthy controls (n=46), all with a request for HLA-A, B, C, DR. Typing was performed using HLA-PCR/SSO LifeCodes and analyzed on the LUMINEX IS100/200 xMAP® system. (Ethics/Code HMC2022-014). RESULTS: One hundred thirty-eight alleles were included from 69 individuals, 43,5% women, aged 44,5±16,5 years in patients with PsA, with a mean age of disease onset of 33.4±14 years. Only 9.5% had a high Body Mass Index and dyslipidemia was the most frequent comorbidity (34.8%), followed by high blood pressure (26,1%). 82% debuted with skin manifestation and once the joint disease was established, the predominance was peripheral (74%) due to arthritis/arthralgia in 74%, enthesitis in 30% and dactylitis in 13%. The allele frequencies were for HLA*A 2402 (13%), 3201 (13%) and 2427 (8,7%), for HLA*B 1402 (17,4%), 4002 (17,4%), 3801 (13%) and HLA*DR 0404 (17,4%), 0407 (13%). No HLA*B27 was identified and HLA*C0602 was only 2,2%. HLA A*0201 and DR*1301 were less frequent in controls versus PsA (p=0.024 and 0,029, respectively), while HLA*B1302 was frequent in PsA (p=0,035). CONCLUSIONS: Curiously, there were no positive results for HLAB*27, which may be related to the population mix. HLA Cw6 is traditionally associated with psoriasis. However, its absence has been linked to nail disorders and PsA; consequently, in our study, it had a low frequency (2,2%). On the other hand, HLA*B1302 has been related to the disease and its early onset; in the healthy Colombian population, it has been described in 0,92%; in our group, it is found to be significant in patients without establishing a clinical association. Few previous studies report HLA results in PsA in Colombia.

OBJETIVO: Describir la frecuencia alélica de HLA en APs y asociarlo con variables demográficas y clínicas. MÉTODOS: Estudio retrospectivo de pacientes adultos con diagnóstico de APs (n=23), y controles sanos (n=46), todos con solicitud de HLA-A, B, C y DR. La tipificación se realizó por medio de HLA-PCR/SSO LifeCodes, y se analizó en el sistema LUMINEX IS 100/200 xMAP®. (Ética/Código HMC2022-014). RESULTADOS: Se incluyeron 138 alelos de 69 individuos, 43,5% mujeres, con edad 44,5±16,5 años, en pacientes con APs, con edad media de inicio de la enfermedad de 33,4±14 años. Solo el 9,5% tuvo Índice de Masa Corporal alto y la dislipidemia fue la comorbilidad más frecuente (34,8%), seguida de hipertensión arterial (26,1%). El 82% debutó con manifestación en piel y una vez establecida la enfermedad articular, el predominio fue periférico (74%), por artritis/artralgias en un 74%, entesitis en 30%, y dactilitis 13%. Las frecuencias alélicas fueron para HLA*A 2402 (13%), 3201 (13%) y 2427 (8,7%), para HLA*B 1402 (17,4%), 4002 (17,4%), 3801 (13%) y HLA*DR 0404 (17,4%), 0407 (13%). No se identificó HLA*B27 y HLA*C0602 fue solo del 2,2 %. HLA A*0201 y DR*1301 fueron menos frecuentes en controles versus APs (p=0,024 y 0,029, respectivamente), mientras que HLA*B1302 frecuente en APs (p=0,035). CONCLUSIÓN: Curiosamente no hubo resultados positivos para HLAB*27 y esto puede relacionarse con el mestizaje de la población. HLA Cw6 es tradicionalmente asociado a psoriasis, sin embargo, su ausencia se ha relacionado con mayor reporte de alteraciones ungueales y Aps; como consecuencia, en nuestro estudio tuvo una baja frecuencia (2,2%). Por otro lado, el HLA*B1302 ha tenido relación con la enfermedad y su inicio temprano, en población sana colombiana se ha descrito en 0,92%, en nuestro grupo se encuentra de manera significativa en los pacientes sin establecerse asociación clínica. Pocos estudios previos refieren resultados de HLA en APs en Colombia.

[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.