Short-Term Effect of a New Oral Sodium Hyaluronate Formulation on Knee Osteoarthritis: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial

Objective: the aim of this pilot study was to test the short-term effect of oral supplementation with a sodium hyaluronate with a large spectrum of molecular weights (FS-HA®) on the symptoms and functionality of knee osteoarthritis (OA). Methods: 60 subjects affected by clinical and/or radiological diagnosis of symptomatic knee OA were consecutively enrolled in a randomized, double blind, placebo-controlled, clinical trial. At randomization visit, at day 28 (visit 2), and day 56 (visit 3), the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), the Lequesne Functional Index (LFI) and the Visual Analogue Scale (VAS) for pain (VAS-p) were administered to the enrolled patients. Then, patients were asked how many times they used rescue medications (non-steroidal antinflammatory drugs–NSAIDs and/or anti-pain drugs) during the previous 4 weeks. Finally, the range of knee joint motion (ROM) was also instrumentally measured. Results: In FS-HA® treated subjects, VAS-p, pain and total WOMAC score, LFI and ROM significantly improved compared to the baseline values (p < 0.05). At 60 days, the VAS-p and the pain WOMAC score were significantly lower after FS-HA® treatment when compared with placebo as well (p < 0.05). The FS-HA® treated subjects significantly reduced the weekly use of NSAIDs and/or antipain drugs when compared to the placebo-treated ones (p < 0.05). Conclusion: the oral supplementation with a FS-HA® characterized by a large spectrum of molecular weight was associated with a short-term improvement in symptomatology and functionality of osteoarthritis-affected knees, and associated with a reduction in the use of NSAIDS and anti-pain drugs

Emerging drugs for psoriatic arthritis

Introduction: The majority of Psoriatic Arthritis patients experience a good clinical response to anti-Tumor Necrosis Factor (TNF)-α therapies. However, treatment failure with anti-TNF-α can represent a relevant clinical problem. Areas covered: We review the efficacy and safety profile of biological therapies that have been reported from randomized, controlled trials in phase II and phase III available in Pubmed Database for agents targeting IL-12/23p40 antibody (ustekinumab) and IL-17 (secukinumab), inhibitor of phosphodiesterase 4, (apremilast), and of JAK/STAT pathways (tofacitinib) and CTLA4 co-stimulation (abatacept) in Psoriatic Arthritis. Expert opinion: In Psoriatic Arthritis, main emerging drugs are represented by the fully human monoclonal IL-12/23p40 antibody, ustekinumab, the agent targeting IL-17, secukinumab, and the inhibitor of phosphodiesterase 4, apremilast. Results on T cell co-stimulation inhibition by abatacept are insufficient both in psoriasis and in PsA. In vitro investigations on JAK/STAT pathways in PsA suggest that tofacitinib could represent a further valuable therapeutic option. Emerging biological treatments other than anti-TNF agents, ustekinumab, secukinumab and apremilast appear promising for Psoriatic Arthritis and recent studies have showed a good efficacy and an acceptable safety profile; however, further and long-term studies are advocate

Progress in understanding and utilizing TNF-α inhibition for the treatment of psoriatic arthritis

The improved recognition of pathogenetic molecular mechanisms has led to the use of drugs targeting cytokines in different inflammatory arthropathies as well psoriatic arthritis (PsA). In particular, the progress in knowledge on tumor necrosis factor (TNF)-α in the pathogenesis of PsA has changed the therapeutic approach by use of direct and receptor cytokine antagonists. Currently, infliximab (IFX), adalimumab, etanercept, golimumab and certolizumab pegol represent the five anti-TNF-α available for the treatment of PsA. This review describes evidence on treatment aimed at neutralizing TNF-α in PsA patients, from the first study in 2000 until today, mainly derived from randomized clinical trials. In comparison with traditional therapies, anti-TNF-α agents have shown to have more efficacy both in treating clinical aspects, including enthesitis, dactylitis, joint pain and swelling, axial involvement, nail and skin lesions, and in reducing radiographic progression. Moreover, anti-TNF-α agents have been demonstrated to be reasonably safe in PsA, as confirmed by data derived by different registries

Association between Leeds Dactylitis Index and ultrasonographic features: a multicentre study on psoriatic hand dactylitis

Objectives: The aim of this study was to explore the link between specific sonographic findings and Leeds Dactylitis Index basic (LDI-b) score in psoriatic arthritis (PsA) patients with hand dactylitis. Methods: Ninety-one hand dactylitis were evaluated in a multicentre study for the presence of pain, functional limitation and tenderness (2-point scale) and LDI-b score. Dactylitic fingers were investigated using high-frequency US in grey scale (GS) and power Doppler (PD). According to median LDI-b score value of 12, fingers were then divided into two groups and categorised into quartiles on the basis of the value of ratio of circumference. Results: Dactylitic fingers with a LDI-b score >12 showed a significantly higher prevalence of GS flexor tenosynovitis (p=0.015), PD flexor tenosynovitis (p=0.001) and soft tissue oedema (p=0.004), when compared with those with those with LDI-b score <12. GS synovitis at proximal interphalangeal (PIP) level (p=0.003) showed more frequent in dactylitic fingers with a LDI-b score <12, than those with a higher LDI-b value. Fingers in the fourth quartile showed a significantly higher prevalence of GS flexor tenosynovitis of grade ≥2 (p=0.046) and joint synovitis of grade ≥2 at PIP level (p=0.028). Conclusions: We found that high values of LDI are associated with US flexor tenosynovitis and soft tissue oedema in PsA dactylitis. Results suggest a potential role of PIP joint synovitis in the genesis of hand digital swelling and of extra-articular structures alterations in determining the LDI score

Musculoskeletal Ultrasound in Monitoring Clinical Response to Treatment in Acute Symptomatic Psoriatic Dactylitis: Results from a Multicentre Prospective Observational Study

This observational and prospective study evaluated the clinical correlations of sonographic lesions in consecutive psoriatic arthritis (PsA) dactylitis cases. Eighty-three dactylitic digits were evaluated clinically and sonographically before treatment and at one-month (T1) and three-month (T3) follow-up. Clinical evaluation included the Leeds Dactylitis Index-basic (LDI-b) score and the visual analogue scales for pain (VAS-p) and functional impairment (VAS-FI). High-frequency ultrasound with grey scale (GS) and power Doppler (PD) assessed flexor tenosynovitis (FT), soft tissue oedema (STO), extensor tendon paratenonitis, and joint synovitis. There was a statistically significant correlation between the clinical parameters (VAS-p, VAS-FI, and LDI-b) and FT and STO at T1 and T3. We found statistically significant improvement in FT and STO for the cases with clinically meaningful treatment responses (p &lt; 0.001). After a multiple conditional logistic regression analysis, the only variables that correlated with a T1 clinical response were the resolutions of PD FT (OR 15.66) and PD STO (OR 6.23), while the resolution of PD FT (OR 27.77) and of GS STO (OR 7.29) correlated with a T3 clinical response. The clinical improvements of active dactylitis are linked to the regression of sonographic evidence of extracapsular inflammation (particularly FT and STO)

Effectiveness and safety of secukinumab in 608 patients with psoriatic arthritis in real life: a 24-month prospective, multicentre study

To evaluate in a multicentric Italian cohort of patients with psoriatic arthritis (PsA) on secukinumab followed for 24 months: (1) the long-term effectiveness and safety of secukinumab, (2) the drug retention rate and minimal disease activity (MDA), (3) di\ufb00erences in the outcomes according to the biological treatment line: biologic-na\uefve patients (group A) versus multifailure (group B) patients

Small molecule therapy for managing moderate to severe psoriatic arthritis

The majority of psoriatic arthritis (PsA) patients experience a good clinical response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologic therapies (bDMARDs). However, treatment failure with these drugs can represent a relevant clinical problem. Moreover, in daily clinical practice, the appropriate identification of patients eligible for these agents can be conditioned by numerous aspects, mainly represented by comorbidities, such as history of malignancies, chronic and recurrent infectious diseases. Areas covered: We searched in the PUBMED database and review published data on the efficacy and safety profile of the small molecules, inhibitor of phosphodiesterase 4, apremilast, and of JAK/STAT pathways, tofacitinib, in PsA. Moreover, we report data on the other JAK inhibitor, baricitinib, and the A(3) adenosine receptors agonist, CF101, emerging by studies conducted in psoriasis patients. Expert opinion: In Psoriatic Arthritis, apremilast appears promising for PsA and recent studies have shown a good efficacy and an acceptable safety profile. Data on tofacitinib in PsA are limited. Studies on the small molecules, baricitinib and CF101 are still incomplete and limited to trials conducted in Rheumatoid Arthritis and in psoriasis. Further studies on small molecules and on their underlining mechanisms are advocated in PsA