Difficult-to-treat concept in Psoriatic Arthritis: analysis of two potential definitions in a large group of patients. A cross-sectional study.

OBJECTIVE: The main aim of the study was to evaluate the performance of two proposed criteria for difficult-to-treat (D2T) Psoriatic arthritis (PsA) in a group of patients and to evaluate the agreement between the two sets of criteria. METHODS: We performed a cross-sectional analysis of two longitudinal cohorts of PsA patients, fulfilling the CASPAR criteria with at least 1-year follow-up. A detailed medical history and physical examination were collected for all recruited patients. The proposed criteria for D2T PsA patients were applied in our group. To test the performance of the two sets of criteria, we use an external validator (the absence of patient acceptable symptom state (PASS no)+ physician global assessment (PhGA)≥6 cm). Finally, the agreement between the two sets of criteria was assessed. RESULTS: we evaluated 378 patients with PsA (M/F: 219/159), mean age (range) 58 (19-75) years, median follow-up 6 (4-8) years. Seventy-five (19.8%) patients fulfilled the D2T criteria proposed by Perrotta et al. and 58 (15.3%) the D2T criteria proposed by Kumthekar et al. Both criteria showed a low sensitivity (Perrotta et al.: 37.8%, Kumthekar et al.: 29.7%) but good specificity (Perrotta et al.: 82.1%, Kumthekar et al.: 86.2%) with a comparable performance. Finally, the agreement between the two sets of criteria is substantial (Fleiss's kappa: 0.72) suggesting that both criteria identifies nearly the same group of patients. CONCLUSION: Our study compared two published sets of criteria showing comparable performance and substantial agreement. The study may pave the way for other researches in this field.

Psoriatic Arthritis Acceptable Symptoms State: Does Sex Make a Difference?

INTRODUCTION: The Patient Acceptable Symptoms State (PASS) is a validated instrument that is used to assess whether a patient with psoriatic arthritis (PsA) accepts her/his disease status by asking them a simple question: "Think about all the ways your PsA has affected you during the last 48 h. If you were to remain in the next few months as you were during the last 48 h, would this be acceptable to you?" The aim of the present study was to explore any PASS differences in patients with PsA based on sex by looking at the corresponding thresholds of Disease Activity for Psoriatic Arthritis (DAPSA), Psoriatic Arthritis Impact of the Disease-12 (PsAID-12) and the Health Assessment Questionnaire-Disability Index (HAQ-DI) in female and male patients. METHODS: This was a cross-sectional study that included two PsA cohorts. To identify the DAPSA, PsAID and HAQ-DI thresholds that differentiated patients who reported "yes" in response to the PASS question from those who reported "no," we used the receiver operating characteristic curves both for the female and male sexes. Moreover, Cohen's kappa test was used to determine the agreement of a PASS "yes" with DAPSA ≤ 14, PsAID ≤ 4 and HAQ-DI ≤ 0.5. RESULTS: Three-hundred ten patients were considered for the study. The DAPSA, PsAID-12 and HAQ-DI thresholds that differentiated PASS "yes" patients from PASS "no" patients were 11.7, 1.85 and 0.625 in male patients and 13.3, 3.85 and 0.750 in female patients, respectively. A PASS "yes" and DAPSA ≤ 14 showed moderate agreement in males (kappa = 0.56) and good agreement in females (kappa = 0.80); the agreement between a PASS "yes" and PsAID ≤ 4 and between a PASS "yes" and HAQ-DI ≤ 0.5 was higher in female patients (moderate). CONCLUSION: Female patients accept their disease at higher DAPSA, PsAID and HAQ-DI values than male patients do. The clinical meaning of this could be that a female patient generally has a greater global disease acceptance inclination. Therefore, this study further supports the concept that sex differences are present in patients with PsA.

Male Fertility in Spondyloarthritis: from Clinical Issues to Cytokines Milieu. A Narrative Review.

PURPOSEOF REVIEW: Male fertility is an emergent issue that should be considered in clinical practice, when dealing with chronic inflammatory diseases in young men. As it is known, the chronic inflammation is the main pathophysiologic mechanism in some rheumatological conditions such as spondyloarthritis (SpA), Ankylosing Spondylitis (AS) and Psoriatic Arthritis (PsA). Therefore, it is paramount to be aware if these diseases could impair male fertility, both due to the inflammation or to the treatments needed: we reviewed the literature on the most relevant and recent evidence on male fertility in patients affected by SpA, AS and PsA. RECENT FINDINGS: Rheumatological inflammatory diseases (included SpA, AS and PsA) could impair the family planning in man life, especially when diagnosed at young age. Moreover, focusing on sperm quality, it seems that a link between sperm quality impairment and a higher disease activity exist. Focusing on therapies, Tumor Necrosis Factor inhibitors showed a safety profile on human male fertility in clinical studies. Recently, a prospective study and two double-blind placebo-controlled trials assessed the impact of methotrexate and Filgotinib on semen parameters, respectively, showing a safety profile of these drugs on human semen quality. However, there are no clinical data on the impact of Interleukin (IL)17 inhibitors(i), IL12-23i and IL23i. Concerning male fertility in SpA, AS and PsA, an unmet clinical need is still present and new studies are needed to understand the association between these diseases and male fertility, and the implication of the therapies used for these diseases. This narrative review provides an overview of the available data on male fertility in patients affected by SpA, AS and PsA.

Clinical Characteristics of "Severe" Peripheral Psoriatic Arthritis: A Retrospective Analysis of a Longitudinal Cohort.

INTRODUCTION: The concept of severity in a multidomain disease such as psoriatic arthritis (PsA) is still not well defined. The aim of this study was to identify the clinical characteristics of patients with severe peripheral PsA. METHODS: Retrospective analysis of a longitudinal cohort. Demographic and clinical characteristics of patients with PsA were collected at baseline and at last follow-up. We defined the severe population using the modified Composite Psoriatic Disease Activity Index (mCPDAI); which excludes ankylosing spondylitis quality of life scale). Hence, patients with a score of 3 in at least one domain were defined as having severe PsA. Clinical characteristics of patients fulfilling the definition of severe PsA were compared to those non-severe. RESULTS: We evaluated 177 patients with peripheral PsA (M/F: 98/76). Of these, 64 (36.1%) were identified as severe according to the mCPDAI criteria, at baseline. Eighteen patients (10.1%) at last follow-up still met the definition of severe PsA. At last follow-up visit, severe patients with PsA were only males (18/18, P < 0.01) and have worse outcomes in terms of disease activity, pain, function, and impact of disease. Male sex and the severity of skin involvement at baseline were factors associated with the presence of severe PsA. The agreement between the presence of severe PsA and the absence of minimal disease activity was slight [Cohen's k: 0.174 (0.084-0.264)]. CONCLUSIONS: Our study showed that severe patients with PsA had more disease activity, pain, and impact of disease than non-severe patients. Furthermore, we demonstrated that severity and disease activity are not interchangeable concepts.

Assessment of Patient-Physician Interactions in Psoriatic Arthritis: National Results of the ASSIST Study.

INTRODUCTION: An overarching principle for the management of psoriatic arthritis (PsA) is a shared decision-making process between physicians and patients. The aim of this study is to assess the patient-physician relationship in a group of patients with PsA, by using the Perceived Efficacy in Patient-Physician Interactions (PEPPI) and CollaboRATE instruments. METHODS: This is a cross-sectional multicenter study where consecutive patients with PsA were enrolled. For each patient, the main demographic, comorbid conditions, and clinical data were collected, including the assessment of disease activity, function, quality of life, and impact of disease. PEPPI and CollaboRATE questionnaires were used, respectively, to evaluate the patient's perception of the patient-physician relationship and the shared decision-making process. RESULTS: A total of 81 patients with PsA were enrolled at four centers in Italy. Overall, our patients showed a high level of confidence in obtaining needed health care, with relatively high median (IQR) values of PEPPI (20; 16-23), and a good shared decision-making process, with high median (IQR) values of CollaboRATE questionnaire (7; 6-9). PEPPI and CollaboRATE scores showed a statistically significant inverse correlation with different clinical variables such as disease duration, Leeds Enthesitis Index, PsA impact of Disease, Health Assessment Questionnaire, pain, patient's global assessment of disease activity and clinical disease activity for PsA. The presence of comorbidities did not appear to be associated with lower values of PEPPI and CollaboRATE. CONCLUSIONS: In this study, few patients with PsA were at risk of suboptimal communication with their physician. This phenomenon appeared to be primarily related to higher disease activity and burden.

The assessment of the drug retention rate of secukinumab in patients with psoriatic arthritis in a real-life multicentre cohort.

OBJECTIVES: We aimed to evaluate the drug retention rate (DRR) of secukinumab, an anti-IL-17A monoclonal antibody, in patients with psoriatic arthritis (PsA) in a real-life cohort, and to assess the impact of comorbidities and patient clinical characteristics on the DRR of secukinumab. METHODS: A retrospective study of prospective followed-up patients was performed to evaluate the DRR of secukinumab on patients with PsA attending the recruiting centres between January 2016 and June 2022. RESULTS: In 207 patients with PsA, a 60-month DRR of secukinumab of 57.0% was estimated (mean time of administration of 21.5±17.1 months). Male gender, age ≥65 years, disease duration ≥5 years and ≥10 years did not influence the DRR of secukinumab. The presence of comorbidities, considering any concomitant disorder, did not affect the DRR of secukinumab. In patients with cardiometabolic multimorbidity, a trend toward a better DRR of secukinumab was recorded. In fact, patients with high blood pressure, dyslipidaemia, and type 2 diabetes showed a trend toward an improved DRR of secukinumab. Furthermore, the presence of obesity did not influence the DRR of secukinumab. Different dosages, previous bDMARDs, and concomitant therapy with csDMARDs did not influence the DRR of secukinumab. CONCLUSIONS: A cumulative 60-month DRR of secukinumab of 57.0% in patients with PsA was retrieved. The presence of cardiometabolic multimorbidity could be associated with an improved DRR of secukinumab, whereas obesity did not affect this feature in our cohort. Previous bDMARDs, concomitant csDMARDs, and different drug dosages could not influence the DRR of secukinumab over time.

Sensitivity and Specificity of Composite Indices of Remission in Male and Female Patients With Psoriatic Arthritis: A Multicenter Cross-Sectional Study of Longitudinal Cohorts.

OBJECTIVE: The aim was to evaluate the sex differences in sensitivity, specificity, positive and negative predictive values, and likelihood ratio of the outcome indices minimal disease activity (MDA), Disease Activity Score for Psoriatic Arthritis (DAPSA), and Psoriatic Arthritis Impact of Disease (PsAID) with respect to clinical remission, evaluated from both the physician and patient perspective, in a multicenter cohort of patients with PsA. METHODS: In this cross-sectional analysis of 2 longitudinal cohorts, all patients with PsA consecutively attending our rheumatology units were considered potentially eligible for the study. In all patients, a complete clinical examination was carried out. The DAPSA was calculated for each patient (DAPSA values ≤ 4 were considered as remission) and MDA was also evaluated. Patient and physician global assessment values ≤ 1 were considered as a surrogate of remission from the patient and physician perspective, respectively. RESULTS: Two hundred seventy-two patients with PsA were enrolled (mean age 55.7 [SD 12.4]; 141 male, 131 female). In both sexes, MDA had good sensitivity and specificity toward remission as assessed by the rheumatologist. Remission according to DAPSA had excellent values of specificity but lacks sensitivity in both sexes. PsAID ≤ 4 had excellent values of sensitivity but lacked specificity in both sexes. Remission defined by DAPSA values was found to be more sensitive and specific in female patients (45.4% and 100%, respectively) than in male patients (33.3% and 84.2%, respectively) with respect to physician-judged remission. CONCLUSION: The results of this study demonstrate for the first time, to our knowledge, that some differences between the 2 sexes on the different outcome indices are possible. This could be important in the clinical management of patients with PsA.

Identification of the Minimal Disease Activity Domains Achieved Based on Different Treatments in Psoriatic Arthritis.

INTRODUCTION: The aim of this work is to characterize which Minimal Disease Activity (MDA) domains are mainly achieved, based on different treatments, in psoriatic arthritis (PsA) patients. Moreover, the association between MDA achievement and the different treatment groups was assessed. METHODS: We conducted a cross-sectional analysis of two longitudinal PsA groups. Inclusion criteria were: age ≥ 18 years, PsA diagnosis, stable treatment for at least 6 months. Patients were grouped depending on the therapy: group 1: Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)/cyclooxygenase 2 inhibitors (COX2i)/steroids, group 2: conventional synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs), group 3: Tumor Necrosis Factor α  inhibitors (TNFi), group 4: interleukin inhibitors (IL)12-23i or IL-23i, group 5: IL-17i, group 6: phosphodiesterase 4 inhibitors (PD4i). For each group, the achieved domains based on therapy were assessed. Multivariate logistic regression analysis was performed to assess the association between the treatment groups and the MDA achievement. RESULTS: A total of 220 patients were enrolled, and MDA was achieved in 45.8% of them. In all treatment groups, the first MDA domains achieved were: body surface area ≤ 3, swollen joint count ≤ 1 and Leeds Enthesitis Index ≤ 1, while MDA domains less frequently achieved were Patient Global Assessment (PtgA) ≤ 2 cm and pain on visual analogue scale ≤ 1.5 cm. The logistic regression analysis showed higher odds ratios for the achievement of the MDA in those patients in groups 3 and 4. CONCLUSIONS: In each treatment group, MDA domains less frequently achieved were PtGA and pain, suggesting that "patient-driven domains" are still an unmet need. Due to the study design and the low number of patients in some groups, it is not possible to clearly define which MDA domain was achieved or not based on treatment; however, it seems that some differences could be present. If larger and prospective studies confirm our preliminary results, we could move toward a personalized/domain treatment approach in PsA.

Triple jump for the optimal management of psoriatic arthritis: diet, sleep and exercise - a review.

Psoriatic arthritis (PsA) is a complex, multiform and chronic inflammatory disease characterised by the association of arthritis and psoriasis combined with other related conditions and comorbidities. Treatment of PsA has rapidly evolved by the introduction of new biological drugs and small molecules which allow to achieve disease remission or low disease activity in most of the patients. However, unmet treatment needs still persist for those patients with persistent disease activity or symptoms, impaired function, reduced quality of life or comorbidities. In this context, non-pharmacological approaches, including diet modifications, an adequate sleep quality and physical activity could provide additional benefits. In recent years, diet modifications, improvement of sleep quality and physical activity became an area of interest for researchers and some studies showed how a holistic non-pharmacological approach may ameliorate the quality of life of patients with PsA.The aim of this manuscript was to review the current evidence on the intriguing link and potential effects of diet, sleep and exercise in PsA patients. In particular, we reviewed the literature focusing on the possible benefits of a holistic approach to PsA patients considering lifestyle modifications.

Difficult to Treat and Refractory to Treatment in Psoriatic Arthritis.

Psoriatic arthritis (PsA) is a complex and chronic inflammatory condition in which the achievement of the best possible disease control has been proposed as the treatment target, which includes the possibility of reaching remission in all disease domains. However, due to the complexity of this multidomain disease, some patients may still have high disease activity in one or more domain and a high burden of disease, potentially leading to various treatment changes and to difficulty with the overall management. In this paper, we overview the concept of patients with difficult-to-treat PsA and the concept of patients with refractory-to-treatment PsA by providing a distinction between these two concepts and the possible implication for the management of patients with PsA.

Ultrasonographic Evaluation of Entheseal Fibrocartilage in Patients with Psoriatic Arthritis, Athletes and Healthy Controls: A Comparison Study.

The aims of this study were as follows: (1) To evaluate the entheseal fibrocartilage (EF) during Achilles tendon insertion in patients with Psoriatic Arthritis (PsA) by using power Doppler ultrasound (PDUS), (2) to assess the intra and inter-reader reliability of the evaluation of EF thickness, (3) to compare the EF thickness of PsA patients, athletes and healthy controls (HCs), and (4) to evaluate the correlations between EF abnormalities, disease activity and functional indices in PsA. METHODS: Consecutive PsA patients attending our unit were asked to participate. HCs and agonist athletes were enrolled as a control group. A bilateral PDUS evaluation of Achilles tendons was performed in order to evaluate the EF in all patients and controls. RESULTS: In total, 30 PsA patients, 40 athletes and 20 HCs were enrolled. The median (IQR) EF thickness among the PsA patients, athletes and HCs was 0.035 cm (0.028-0.04) cm, 0.036 (0.025-0.043) cm and 0.030 (0.020-0.038) cm, respectively (p = 0.05 between PsA patients and HCs). The intra-reader reliability was excellent [ICC (95% CI) of 0.91 (0.88-0.95)] and the inter-reader reliability was good (0.80 (0.71-0.86). The assessment of EF was feasible, with a mean time of 2 min. No correlations were found with disease activity indices in PsA patients. CONCLUSION: The assessment of EF is a feasible and reproducible test and may be explored as a potential imaging biomarker.

Psoriatic Arthritis in Males and Females: Differences and Similarities.

OBJECTIVE: To assess any differences and similarities in psoriatic arthritis (PsA) between sexes. Any possible differences of psoriasis and its potential impact on disease burden between sexes with PsA were also evaluated. METHODS: Cross-sectional analysis of two longitudinal PsA cohorts. The impact of psoriasis on the PtGA was evaluated. Patients were stratified in four groups based on BSA. The median PtGA was then compared between the four groups. Moreover, a multivariate linear regression analysis was performed in order to evaluate associations between PtGA and skin involvement, split by sexes. RESULTS: We enrolled 141 males and 131 females: PtGA, PtPnV, tender, swollen joint count, DAPSA, HAQ-DI, PsAID-12 were statistically significant higher in females (p ≤ 0.05). PASS "yes" was deemed more in males than in females and BSA was higher in males. MDA was present more in males than females. When the patients were stratified on BSA, median PtGA was not different between males and females with BSA = 0. Instead, in females with BSA > 0, a higher PtGA was observed compared to males with BSA > 0. There was not a statistically significant association between skin involvement and PtGA at linear regression analysis, even if a trend seems to be present in female. CONCLUSIONS: Psoriasis is more present in males, but it seems to be related to a worse impact in females. In particular, a possible role of psoriasis as an influencing factor the PtGA was found. Moreover, female PsA patients tended to have more disease activity, worse function, and higher disease burden.

Cardiovascular comorbidities in psoriatic arthritis: epidemiology and risk factors in two different European populations.

OBJECTIVES: Psoriatic arthritis (PsA) is a chronic inflammatory disease, frequently associated with cardiovascular (CV) comorbidities. Our aim was to compare the prevalence of CV comorbidities between two groups of PsA patients from different European countries: Belgium and Italy. METHODS: This is a cross-sectional analysis of two longitudinal cohorts in which 803 PsA patients were enrolled (463 from Belgium and 340 from Italy). All enrolled patients were ≥18 years old and fulfilled the ClASsification criteria for Psoriatic Arthritis (CASPAR criteria). For each patient, demographics, clinical assessments, smoking habits, the presence of arterial hypertension (AH), obesity (BMI ≥30), type 2 diabetes (T2D), CV diseases (acute myocardial infarction, stroke or transient ischaemic attack), dyslipidaemia (Italy only) and hypercholesterolaemia (Belgium only) were collected. RESULTS: The most prevalent comorbidities among Italian patients with PsA were: AH (45.1%), dyslipidaemia (38.6%) and obesity (30.8%), and among Belgian patients were: hypercholesterolaemia (30.9%), obesity (27%) and AH (26.4%). Moreover, the prevalence of T2D and CV diseases was respectively 14.2% and 7.1% among Italian patients and 7.6% and 3.5% among Belgian patients. When comparing the two groups, AH, T2D and CV diseases were significantly more prevalent in Italian PsA patients. After controlling for different confounders, Italian patients, regardless of age, sex, smoking habits, PsA duration, other CV comorbidities, therapy, disease activity and function, had a higher risk to be hypertensive (OR 2.00, p=0.007). Instead of the country in which patients lived was not a predictor for the risk of T2D and CV diseases. Obesity prevalence was not different between the two groups. The lipid profile was unfavourable in both populations (even if not comparable between the two groups, due to the different way of collection), as is often the case in PsA. CONCLUSIONS: The prevalence of AH, T2D and CV diseases were higher in Italian patients rather than Belgians. Moreover, among patients with PsA, the risk of AH was higher in the Italian cohort compared to the Belgian cohort. These results suggest that further research is needed to evaluate potential extrinsic factors (geography and sociocultural aspects) that may contribute to CV risk.

The Conundrum of Psoriatic Arthritis: a Pathogenetic and Clinical Pattern at the Midpoint of Autoinflammation and Autoimmunity.

Psoriatic arthritis (PsA) is a chronic inflammatory condition characterized by psoriasis, synovitis, enthesitis, spondylitis, and the possible association with other extra-articular manifestations and comorbidities. It is a multifaceted and systemic disorder sustained by complex pathogenesis, combining aspects of autoinflammation and autoimmunity. Features of PsA autoinflammation include the role of biomechanical stress in the onset and/or exacerbation of the disease; the evidence of involvement of the innate immune response mediators in the skin, peripheral blood and synovial tissue; an equal gender distribution; the clinical course which may encounter periods of prolonged remission and overlapping features with autoinflammatory syndromes. Conversely, the role of autoimmunity is evoked by the association with class I major histocompatibility complex alleles, the polyarticular pattern of the disease which sometimes resembles rheumatoid arthritis and the presence of serum autoantibodies. Genetics also provide important insights into the pathogenesis of PsA, particularly related to class I HLA being associated with psoriasis and PsA. In this review, we provide a comprehensive review of the pathogenesis, genetics and clinical features of PsA that endorse the mixed nature of a disorder at the crossroads of autoinflammation and autoimmunity.

Dactylitis and Early Onset Psoriasis in Psoriatic Arthritis: Are they Markers of Disease Severity? A Clinical Study.

OBJECTIVES: To stratify psoriatic arthritis (PsA) patients based on psoriasis (PsO) onset age: early onset psoriasis (EOP) vs. late onset psoriasis (LOP), and to assess if there are differences in disease characteristics, activity/function/impact of the disease, and comorbidity indices. METHODS: Cross-sectional analysis of a longitudinal PsA cohort. Patients were stratified based on PsO onset age. RESULTS: One hundred and sixty PsA patients were enrolled (84 in EOP and 76 in LOP group) in the study. EOP PsA patients seem to have an increased probability to have dactylitis rather than LOP ones, OR 9.64 (3.77-24.6). Comorbidity indices (Rheumatic Disease Comorbidity Index and Charlson Comorbidity Index) were higher in LOP PsA patients, but these data were not confirmed when adjusted by age and sex. There are also differences in the treatment regimen: EOP PsA patients were more frequently treated with anti-interleukin (IL) 17; instead, LOP patients were more frequently treated with non-steroid anti-inflammatory drugs and conventional synthetic disease-modifying anti-rheumatics drugs. There were no differences in the disease activity, function, or impact of the disease. CONCLUSIONS: There are some clinical and therapeutic differences in PsA patients linked to the PsO onset age, namely dactylitis in EOP. Other characteristics found were: a "comorbidities trend" in LOP patients and a more frequent use of anti-IL17 in EOP.

Clinical Characteristics of Potential "Difficult-to-treat" Patients with Psoriatic Arthritis: A Retrospective Analysis of a Longitudinal Cohort.

INTRODUCTION: The EULAR group recently published the definition of difficult-to-treat (D2T) patients for rheumatoid arthritis. However, a similar definition is lacking for patients with psoriatic arthritis (PsA), in which its multi-domain expression may impact the treatment response. The aim of the study was to characterize the potential D2T PsA patients, to assess the risk factors, and to determine the burden of disease. METHODS: Retrospective analysis of a longitudinal cohort of PsA patients attending a tertiary care center. At each visit, the patients underwent a complete physical examination and the clinical/laboratory data were collected. Data on comorbidities with the assessment of different comorbidity indices were also collected. Disease activity was assessed by using the DAPSA score and the MDA. The PsAID and HAQ-DI were also collected. We use the previous identified definition of D2T patients, applied to our PsA group and modified for this study. RESULTS: A total of 106 patients fulfilled the inclusion criteria and were evaluated. Of these, 36 (33.9%) patients fulfilled the criteria for the potential D2T patients. D2T patients showed a significantly higher BMI and higher prevalence of fibromyalgia. Furthermore, D2T patients showed a significantly higher median Functional Comorbidity Index and a significantly higher BSA, LEI, pain level, PsAID score, and HAQ-DI than non-D2T patients. Potential D2T patients also showed a significant delay in the time from diagnosis to first b/ts DMARDs treatment. CONCLUSIONS: Our study firstly evaluated the presence of clinical characteristics of potential D2T patients and may contribute to future research on this intriguing aspect.

Therapeutic Targets for Ankylosing Spondylitis - Recent Insights and Future Prospects.

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease belonging to the axial spondyloarthritis (axSpA), a group of diseases that affects the axial skeleton and causes severe pain and disability. An early diagnosis and appropriate treatment can reduce the severity of the disease and the risk of progression. TNF-α inhibitors demonstrated efficacy and effectiveness in axSpA patients by reducing disease activity, minimizing inflammation and improving the quality of life. More recently, new insights in pathogenesis of axSpA, including the discovery of the role of IL-23/IL-17 axis and intracellular pathways, led to the development of new biologics and small molecules that improve our therapeutic armamentarium. New alternatives are also being soon available. The aim of this paper is to narratively review the recent insights and future prospects in the treatment of AS and, more in general, axSpA.

Extra-Articular Manifestations and Comorbidities in Psoriatic Disease: A Journey Into the Immunologic Crosstalk.

Psoriatic arthritis (PsA) is a chronic inflammatory disease primarily affecting peripheral and axial joints, with the possible presence of extra-articular manifestations (EAMs), such as psoriasis, uveitis, and inflammatory bowel disease. Recently, the concept of psoriatic disease (PsD) has been proposed to define a systemic condition encompassing, in addition to joints and EAMs, some comorbidities (e.g., metabolic syndrome, type II diabetes, hypertension) that can affect the disease outcome and the achievement of remission. EAMs and comorbidities in PsA share common immunopathogenic pathways linked to the systemic inflammation of this disease; these involve a broad variety of immune cells and cytokines. Currently, various therapeutics are available targeting different cytokines and molecules implicated in the inflammatory response of this condition; however, despite an improvement in the management of PsA, comprehensive disease control is often not achievable. There is, therefore, a big gap to fill especially in terms of comorbidities and EAMs management. In this review, we summarize the clinical aspects of the main comorbidities and EAMs in PsA, and we focus on the immunopathologic features they share with the articular manifestations. Moreover, we discuss the effect of a diverse immunomodulation and the current unmet needs in PsD.