Dual targeted therapy in patients with psoriatic arthritis and spondyloarthritis: a real-world multicenter experience from Spain.

Dual targeted therapy (DTT) has emerged as a promising approach in patients with refractory spondyloarthritis (SpA) or psoriatic arthritis (PsA) and extra-musculoskeletal manifestations of both diseases, but its effectiveness/safety ratio still remains unclear. This is a retrospective, real-world multicenter study in refractory SpA and PsA patients with simultaneous use of two biological or synthetic targeted agents. Effectiveness was assessed using Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) and Disease Activity in Psoriatic Arthritis (DAPSA) Score. We identified 39 different DTT combinations in 36 patients (22 SpA; 14 PsA), 25 of them with concomitant inflammatory bowel disease. The most commonly used combinations were TNF inhibitor plus antagonist of the IL12/23 pathway, followed by TNF inhibitor plus IL-17 antagonist. During a median exposure of 14.86 months (IQR 8-20.2), DTT retention rate was 69.4% (n=25/36; 19 SpA, 6 PsA). Major clinical improvement (change in ASDAS-CRP > 2 or improvement > 85% in DAPSA) was achieved in 69.4% of patients (n=25/36 therapeutical combinations; 17/21 SpA, 8/15 PsA), with a 58.3% (n=21/36 combinations; 15/20 SpA, 6/13 PsA) low-activity/remission rate. Of the patients who were receiving glucocorticoids, 55% managed to withdraw them during follow-up. Interestingly, only four serious adverse events in three patients were observed, leading to DTT discontinuation.

Improvement in patient-reported outcomes and work productivity following 3-year ustekinumab or tumour necrosis factor inhibitor treatment in patients with psoriatic arthritis: results from the PsABio real-world study.

BACKGROUND: To evaluate the real-world effect of the IL-12/23 inhibitor ustekinumab or of a tumour necrosis factor inhibitor (TNFi) on patient-reported outcomes (PRO) and their association with effectiveness endpoints in psoriatic arthritis (PsA) patients over 3 years. METHODS: In PsABio (NCT02627768), a prospective, observational study, patients with PsA that were prescribed first- to third-line ustekinumab or a TNFi, and remained on that drug for 3 years, were analysed for change in baseline in PROs (EuroQol-5 dimensions health state VAS [EQ-5D VAS], 12-item Psoriatic Arthritis Impact of Disease questionnaire [PsAID-12; range 0-10], Work Productivity and Activity Impairment for Psoriatic Arthritis questionnaire [WPAI; results expressed as a percentage for each domain]), and the association between PROs and WPAI with effectiveness endpoints, clinical disease activity index for psoriatic arthritis (cDAPSA), low disease activity (LDA)/remission, minimal disease activity (MDA) and very low disease activity (VLDA). RESULTS: In 437 patients (mean age 49.1 years, 47.8% female), at 3 years, ustekinumab and TNFi treatment led to comparable improvements in EQ-5D VAS; mean change from baseline (95% confidence intervals [CI]) was 11.0 (6.5; 15.4) and 18.9 (14.0; 23.9), respectively. Both groups improved PsAID-12 after 3 years; mean change from baseline (95% CI) was -2.9 (-3.2; -2.5) and -3.5 (-3.9; -3.2), respectively. At baseline, due to their PsA, TNFi-treated patients had lower work productivity compared to ustekinumab-treated patients; mean productivity reduction (95% CI) was 58.8 [52.4; 65.2] and 43.3 [35.6; 51.1]. Over 3 years, TNFi-treated patients had a greater improvement in work productivity compared to ustekinumab-treated patients, ultimately leaving work productivity to be comparable between groups; mean improvement (95% CI) was 44.5% (38.4; 50.6) and 24.9% (15.8; 34.0), respectively. A similar trend was observed in activity impairment. Patients in both treatment groups who achieved effectiveness endpoints, cDAPSA LDA/remission, MDA, and VLDA had greater improvement in PROs and WPAI than patients who did not achieve these endpoints. CONCLUSIONS: At 3 years, improvements in PROs following ustekinumab or TNFi treatment were generally comparable; however, TNFi-treated patients achieved a greater improvement in work productivity, although this group started from a lower baseline. Achievement of effectiveness endpoints, independent of treatment group, also improved PROs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02627768. Registered on 11 December 2015.

Moderate-High Disease Activity in Patients with Recent-Onset Psoriatic Arthritis-Multivariable Prediction Model Based on Machine Learning.

The aim was to identify patient- and disease-related characteristics predicting moderate-to-high disease activity in recent-onset psoriatic arthritis (PsA). We performed a multicenter observational prospective study (2-year follow-up, regular annual visits) in patients aged ≥18 years who fulfilled the CASPAR criteria and had less than 2 years since the onset of symptoms. The moderate-to-high activity of PsA was defined as DAPSA > 14. We trained a logistic regression model and random forest-type and XGBoost machine learning algorithms to analyze the association between the outcome measure and the variables selected in the bivariate analysis. The sample comprised 158 patients. At the first follow-up visit, 20.8% of the patients who attended the clinic had a moderate-to-severe disease. This percentage rose to 21.2% on the second visit. The variables predicting moderate-high activity were the PsAID score, tender joint count, level of physical activity, and sex. The mean values of the measures of validity of the machine learning algorithms were all high, especially sensitivity (98%; 95% CI: 86.89-100.00). PsAID was the most important variable in the prediction algorithms, reinforcing the convenience of its inclusion in daily clinical practice. Strategies that focus on the needs of women with PsA should be considered.

Gender-specific differences in patients with psoriatic arthritis receiving ustekinumab or tumour necrosis factor inhibitor: real-world data.

OBJECTIVE: Investigate effects of gender on disease characteristics and treatment impact in patients with PsA. METHODS: PsABio is a non-interventional European study in patients with PsA starting a biological DMARD [bDMARD; ustekinumab or TNF inhibitor (TNFi)]. This post-hoc analysis compared persistence, disease activity, patient-reported outcomes and safety between male and female patients at baseline and 6 and 12 months of treatment. RESULTS: At baseline, disease duration was 6.7 and 6.9 years for 512 females and 417 males respectively. Mean (95% CI) scores for females vs males were: clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA), 32.3 (30.3, 34.2) vs 26.8 (24.8, 28.9); HAQ-Disability Index (HAQ-DI), 1.3 (1.2, 1.4) vs 0.93 (0.86, 0.99); total PsA Impact of Disease-12 (PsAID-12) score, 6.0 (5.8, 6.2) vs 5.1 (4.9, 5.3), respectively. Improvements in scores were smaller in female than male patients. At 12 months, 175/303 (57.8%) female and 212/264 (80.3%) male patients achieved cDAPSA low disease activity, 96/285 (33.7%) and 137/247 (55.5%), achieved minimal disease activity (MDA), respectively. HAQ-DI scores were 0.85 (0.77, 0.92) vs 0.50 (0.43, 0.56), PsAID-12 scores 3.5 (3.3, 3.8) vs 2.4 (2.2, 2.6), respectively. Treatment persistence was lower in females than males (P ≤ 0.001). Lack of effectiveness was the predominant reason to stop, irrespective of gender and bDMARD. CONCLUSIONS: Before starting bDMARDs, females had more severe disease than males and a lower percentage reached favourable disease states, with lower persistence of treatment after 12 months. A better understanding of the mechanisms underlying these differences may improve therapeutic management in females with PsA. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02627768.

Long-term effectiveness and persistence of ustekinumab and TNF inhibitors in patients with psoriatic arthritis: final 3-year results from the PsABio real-world study.

OBJECTIVES: To evaluate real-world persistence and effectiveness of the IL-12/23 inhibitor, ustekinumab or a tumour necrosis factor inhibitor (TNFi) for psoriatic arthritis over 3 years. METHODS: PsABio (NCT02627768), a prospective, observational study, followed patients with PsA prescribed first-line to third-line ustekinumab or a TNFi. Persistence and effectiveness (achievement of clinical Disease Activity for PSA (cDAPSA) low disease activity (LDA)/remission and minimal disease activity/very LDA (MDA/VLDA)) were assessed every 6 months. Safety data were collected over 3 years. Analyses to compare the modes of action were adjusted on baseline differences by propensity scores (PS). RESULTS: In 895 patients (mean age 49.8 years, 44.7% males), at 3 years, the proportion of patients still on their initial treatments was similar with ustekinumab (49.9%) and TNFi (47.8%). No difference was seen in the risk of stopping/switching; PS-adjusted hazard ratio (95% CI) for stopping/switching ustekinumab versus TNFi was 0.87 (0.68 to 1.11). In the overall population, cDAPSA LDA/remission was achieved in 58.6%/31.4% ustekinumab-treated and 69.8%/45.0% TNFi-treated patients; PS-adjusted ORs (95% CI) were 0.89 (0.63 to 1.26) for cDAPSA LDA; 0.72 (0.50 to 1.05) for remission. MDA/VLDA was achieved in 41.4%/19.2% of ustekinumab-treated and 54.2%/26.9% of TNFi-treated patients with overlapping PS-adjusted ORs. A greater percentage of TNFi-treated patients achieved effectiveness outcomes. Both treatments exhibited good long-term safety profiles, although ustekinumab-treated patients had a lower rate of adverse events (AEs) versus TNFi. CONCLUSION: At 3 years, there was generally comparable persistence after ustekinumab or TNFi treatment, but AE rates were lower with ustekinumab.

Confounders contributing to explain the association between sex and disease impact in patients with recent-onset psoriatic arthritis.

OBJECTIVES: To evaluate the effect of potential confounders on the association between sex and disease impact in recent-onset psoriatic arthritis. METHODS: We performed a multicentre observational prospective study (2-year follow-up, regular annual visits). The study population comprised patients aged ≥18 years who fulfilled the CASPAR criteria and less than 2 years since the onset of symptoms. The dataset was generated using data for each patient at the 3 visits (baseline, first year, and second year of follow-up) matched with the PsAID values at each of the 3 visits. Once variables associated with both PsAID ≥4 and sex were selected, those that led to a difference of >10% between the adjusted and crude estimations were identified as potential confounders in the association between sex and PsAID. Lastly, the final multivariate logistic regression model estimating the association between sex and PsAID was defined. RESULTS: The dataset contained 418 observations (158 at baseline, 135 at the first follow-up visit, and 125 at the second visit). The confounders identified in the multivariate model were HAQ, global pain, level of physical activity, and joint pattern at diagnosis. After adjustment for these variables, no statistically significant association was observed between female sex and PsAID ≥4. CONCLUSIONS: The association between female sex and greater disease impact could be explained by the influence of other variables, specifically higher HAQ score, greater intensity of pain, differences in the level of physical activity and in the joint pattern at diagnosis (lower frequency of the spondylitis pattern in women).

Severe Disease in Patients With Recent-Onset Psoriatic Arthritis. Prediction Model Based on Machine Learning.

Objectives: To identify patient- and disease-related characteristics that make it possible to predict higher disease severity in recent-onset PsA. Methods: We performed a multicenter observational prospective study (2-year follow-up, regular annual visits). The study population comprised patients aged ≥ 18 years who fulfilled the CASPAR criteria and less than 2 years since the onset of symptoms. Severe disease was defined at each visit as fulfillment of at least 1 of the following criteria: need for systemic treatment, Health Assessment Questionnaire (HAQ) > 0.5, polyarthritis. The dataset contained data for the independent variables from the baseline visit and follow-up visit number 1. These were matched with the outcome measures from follow-up visits 1 and 2, respectively. We trained a logistic regression model and random forest-type and XGBoost machine learning algorithms to analyze the association between the outcome measure and the variables selected in the bivariate analysis. Results: The sample comprised 158 patients. At the first follow-up visit, 78.2% of the patients who attended the clinic had severe disease. This percentage decreased to 76.4% at the second visit. The variables predicting severe disease were patient global pain, treatment with synthetic DMARDs, clinical form at diagnosis, high CRP, arterial hypertension, and psoriasis affecting the gluteal cleft and/or perianal area. The mean values of the measures of validity of the machine learning algorithms were all ≥ 80%. Conclusion: Our prediction model of severe disease advocates rigorous control of pain and inflammation, also addressing cardiometabolic comorbidities, in addition to actively searching for hidden psoriasis.

Persistence and effectiveness of the IL-12/23 pathway inhibitor ustekinumab or tumour necrosis factor inhibitor treatment in patients with psoriatic arthritis: 1-year results from the real-world PsABio Study.

OBJECTIVE: We evaluated real-world treatment persistence and effectiveness at 1 year following initiation of IL-12/23 inhibitor ustekinumab or a tumour necrosis factor inhibitor (TNFi) for psoriatic arthritis (PsA). METHODS: PsABio (NCT02627768), a prospective, observational study, followed patients with PsA prescribed first-line to third-line ustekinumab or TNFi. Drug persistence, effectiveness (achievement of clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) low disease activity (LDA)/remission and minimal disease activity/very low disease activity (MDA/VLDA)), and safety were assessed every 6 months. In addition to descriptive statistics, propensity score (PS)-adjusted comparisons across cohorts were performed. RESULTS: At 1 year, overall persistence was similar in the ustekinumab (n=317/438, 72.4%) and TNFi (n=321/455, 70.5%) groups. PS-adjusted HR (95% CI) for stopping/switching ustekinumab versus TNFi was 0.82 (0.60; 1.13). cDAPSA LDA (including remission)/remission was achieved in 55.9%/22.1% of ustekinumab-treated and 67.1%/31.7% of TNFi-treated patients; PS-adjusted ORs (95% CI) were 0.80 (0.57; 1.10) for cDAPSA LDA and 0.73 (0.49; 1.07) for remission. MDA/VLDA was achieved in 34.2%/11.9% of ustekinumab-treated and 43.1%/12.6% of TNFi-treated patients; PS-adjusted ORs (95% CI) were 0.89 (0.63; 1.26) for MDA and 0.90 (0.54; 1.49) for VLDA. The safety profiles were similar in both groups. CONCLUSION: In the real-world PsABio Study, after 1 year of treatment, although unadjusted persistence was numerically slightly higher for ustekinumab versus TNFi and unadjusted effectiveness was numerically slightly higher for TNFi versus ustekinumab, the PS-adjusted comparisons demonstrated comparable overall persistence, effectiveness and safety for both modes of action in PsA.

Effectiveness of IL-12/23 inhibition (ustekinumab) versus tumour necrosis factor inhibition in psoriatic arthritis: observational PsABio study results.

OBJECTIVES: To evaluate 6-month effectiveness of ustekinumab versus tumour necrosis factor inhibitor (TNFi), analysing predictors of low disease activity (LDA)/remission. METHODS: PsABio is a prospective, observational cohort study of patients with psoriatic arthritis (PsA) at 92 sites in eight European countries, who received first-line to third-line ustekinumab or a TNFi. Comparative achievement at 6 months of clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) LDA/remission, and minimal disease activity (MDA)/very LDA using propensity score (PS)-adjusted multivariate logistic regression was assessed. RESULTS: In the final analysis set of 868 participants with 6-month follow-up data (ustekinumab, n=426; TNFi, n=442), with long-standing disease and a high mean cDAPSA score (31.0 vs 29.8, respectively), proportions of patients in ustekinumab/TNFi treatment groups achieving cDAPSA LDA at 6 months were 45.7%/50.7%. cDAPSA remission was achieved in 14.9%/19.2%, and MDA in 26.4%/30.8% of patients. PS-adjusted odds ratios (OR; 95% confidence interval (CI)) of reaching cDAPSA LDA and MDA were 0.73 (0.46 to 1.15) and 0.87 (0.61 to 1.25) with ustekinumab versus TNFi, indicating no significant difference. High baseline body mass index or high cDAPSA were associated with a lower chance (OR (95% CI)) of reaching cDAPSA LDA with TNFi (0.94 (0.89 to 0.99) and 0.64 (0.52 to 0.79), respectively). Predictive factors were similar to previously published evidence, with cDAPSA and 12-item Psoriatic Arthritis Impact of Disease scores and chronic widespread pain at baseline appearing as new risk factors for unfavourable outcome. Safety data were similar between groups. CONCLUSION: Treatment targets were reached similarly after 6 months of treatment with ustekinumab and TNFi.

No radiographic sacroiliitis progression was observed in patients with early spondyloarthritis at 6 years: results of the Esperanza multicentric prospective cohort.

OBJECTIVE: To estimate the 6-year radiographic progression of sacroiliitis in patients with early spondyloarthritis (SpA). PATIENTS AND METHODS: Sacroiliac joint (SIJ) radiographs (baseline and 6 years) of 94 patients with recent-onset SpA from the Esperanza cohort were scored, blindly and in a random order, by nine readers. The modified New York criteria were used to define the presence of sacroiliitis. As the gold standard for radiographic (r) sacroiliitis, the categorical opinion of at least five readers was used. Progression was defined as the shift from non-radiographic (nr) to r-sacroiliitis. RESULTS: In the 94 SIJ radiographs (baseline and 6 years), 78/94 (83%) pairs of radiographs had not changed from baseline to 6 years. Sacroiliitis was present in 20 patients at baseline (21.3%) and in 18 (19.2%) patients at 6 years; 11 patients had sacroiliitis at both the baseline and final visits; 9 patients changed from baseline r-sacroiliitis to nr-sacroiliitis at 6 years, and 7 changed from baseline nr-sacroiliitis to r-sacroiliitis at 6 years. The mean continuous change score (range: -8 to +8) was 2.80 at baseline and 2.55 at 6 years (mean net progression of -0.25). The reliability of the readers was fair (mean inter-reader kappa of 0.375 (0.146-0.652) and mean agreement of 73.7% (58.7-90%)). CONCLUSION: In the early SpA Esperanza cohort, progression from nr-axSpA to r-axSpA over 6 years was not observed, although the SIJ radiographs scoring has limitations to detect low levels of radiographic progression.

Registro Español de Artritis Psoriásica de Reciente Comienzo (estudio REAPSER). Objetivos y metodología / Spanish Registry of Recent-onset Psoriatic Arthritis (REAPSER study): aims and methodology

OBJETIVOS: Describir la metodología del Registro Español de Artritis Psoriásica de reciente comienzo de la Sociedad Española de Reumatología (REAPSER), así como sus fortalezas y limitaciones. El objetivo principal del proyecto es identificar factores pronósticos de la evolución clínica y radiográfica en una cohorte de pacientes que padecen artritis psoriásica (APs) diagnosticada con menos de 2 años de evolución. MATERIAL Y MÉTODO: Estudio observacional, prospectivo (2 años de seguimiento; periodicidad anual de las visitas), multicéntrico. La intención en la visita basal fue reflejar la situación del paciente antes de que la evolución de la enfermedad se viese modificada por los tratamientos pautados en los servicios de reumatología. Los pacientes fueron invitados a participar consecutivamente en una de sus visitas habituales al reumatólogo. El tamaño muestral finalmente alcanzado fue de 211 pacientes. Se recogen datos sociodemográficos; de situación laboral; historia familiar; antecedentes personales y comorbilidad; antropométricos; estilo de vida; uso de los servicios de salud; situación clínica al diagnóstico de APs; afectación articular y dolor espinal; dolor y valoración global de la enfermedad; entesitis, dactilitis y uveítis; afectación cutánea y ungueal; situación funcional y calidad de vida; evaluación radiográfica; determinaciones analíticas; tratamiento; brotes en esqueleto axial y periférico. CONCLUSIONES: El estudio REAPSER incluye una cohorte de pacientes con APs de inicio reciente reclutados antes de que la evolución de la enfermedad se viese modificada por la prescripción de FAME en los servicios de reumatología. Se espera que la información exhaustiva recogida en las visitas suponga una amplia fuente de datos para futuros análisis

AIMS: To describe the methodology of REAPSER (Spanish Registry of Recent-onset Psoriatic Arthritis), its strengths and limitations. The aim of this study is to identify prognostic factors for the clinical and radiographic course in a cohort of patients with psoriatic arthritis (PsA) diagnosed within 2 years of symptom evolution. METHODS: Multicenter, observational and prospective study (with 2-year follow-up including annual visits). Baseline visit intended to reflect patient situation before the disease course was modified by treatments prescribed in rheumatology departments. Patients were invited to participate consecutively in one of their routine visits to the rheumatologist. 211 patients were included. Following data were collected: sociodemographic variables; employment situation; family history; personal history and comorbidities; anthropometric data; lifestyle; use of healthcare services; clinical situation at the time of PsA diagnosis; joint involvement and spinal pain; pain and overall assessment; enthesitis, dactylitis and uveitis; skin and nail involvement; functional situation and quality of life; radiographic evaluation; analytical determinations; treatment; axial and peripheral flare-ups. CONCLUSIONS: The REAPSER study includes a cohort of patients with recent-onset PsA, before the disease course was modified by disease-modifying antirheumatic drugs prescribed in rheumatology departments. Exhaustive information collected in each visit is expected to be an important data source for future analysis

Spanish Registry of Recent-onset Psoriatic Arthritis (REAPSER study): Aims and methodology. / Registro Español de Artritis Psoriásica de Reciente Comienzo (estudio REAPSER). Objetivos y metodología.

AIMS: To describe the methodology of REAPSER (Spanish Registry of Recent-onset Psoriatic Arthritis), its strengths and limitations. The aim of this study is to identify prognostic factors for the clinical and radiographic course in a cohort of patients with psoriatic arthritis (PsA) diagnosed within 2years of symptom evolution. METHODS: Multicenter, observational and prospective study (with 2-year follow-up including annual visits). Baseline visit intended to reflect patient situation before the disease course was modified by treatments prescribed in rheumatology departments. Patients were invited to participate consecutively in one of their routine visits to the rheumatologist. 211 patients were included. Following data were collected: sociodemographic variables; employment situation; family history; personal history and comorbidities; anthropometric data; lifestyle; use of healthcare services; clinical situation at the time of PsA diagnosis; joint involvement and spinal pain; pain and overall assessment; enthesitis, dactylitis and uveitis; skin and nail involvement; functional situation and quality of life; radiographic evaluation; analytical determinations; treatment; axial and peripheral flare-ups. CONCLUSIONS: The REAPSER study includes a cohort of patients with recent-onset PsA, before the disease course was modified by disease-modifying antirheumatic drugs prescribed in rheumatology departments. Exhaustive information collected in each visit is expected to be an important data source for future analysis.

Síndrome de Cogan: descripción de un caso con respuesta parcial a tocilizumab y revisión de la literatura / Cogan's syndrome: A case report with partial response to tocilizumab and a literature review

RESUMEN El síndrome de Cogan (SC) es una enfermedad inflamatoria crónica, caracterizada por queratitis intersticial y síntomas vestíbulo-auditivos similares al síndrome de Meniere, acompañado o no de vasculitis sistémica. Es una enfermedad poco frecuente y su diagnóstico es difícil y a menudo tardío, lo que aumenta el riesgo de secuelas como pérdida visual o cofosis. Además, su tratamiento no está bien establecido y se basa en reportes de casos donde se ha observado la eficacia de fármacos como la ciclofosfamida, anti-TNF o tocilizumab. Presentamos un caso de SC sin respuesta a metotrexato, ciclofosfamida ni anti-TNF, y respuesta parcial a tocilizumab.

ABSTRACT Cogan's syndrome is a chronic inflammatory disease typified by interstitial keratitis and Meniere-like auditory involvement, and it can be accompanied by systemic vasculitis. It's a rare disease and its diagnosis is difficult and often late, which increases the risk of sequelae, such as visual loss or deafness. In addition, its treatment is not well-established and is based on case reports that have observed efficacy of drugs such as cyclophosphamide, anti-TNF or tocilizumab. A case of Cogan's syndrome is presented that did not respond to methotrexate, cyclophosphamide, or anti-TNF, but with a partial response to tocilizumab.