Purpose: To prospectively compare the efficacy and safety of intra-articular injections of platelet-rich plasma (PRP) with hyaluronic acid (HA) and glucocorticosteroid (CS) control groups for knee osteoarthritis (KOA) in a randomized, triple-parallel, single-center clinical trial. Methods: A total of 75 patients were randomly assigned to one of three groups receiving a single injection of either leukocyte-poor platelet-rich plasma (25 knees), hyaluronic acid (25 knees), or glucocorticosteroid (25 knees). The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score was collected at baseline and 6, 12, and 26 weeks after treatment. Results: After 6 weeks of PRP administration, a decrease in the mean WOMAC value was observed in all three study groups. Three months after administration, the greatest decrease in the mean WOMAC value was obtained in the PRP group. The results in the HA and CS groups were similar (p = 0.681). In the one-way analysis of variance and post hoc analysis using the HSD Tukey test, a significantly greater improvement was shown by comparing the PRP and CS groups (p = 0.001), and the PRP and HA groups (p = 0.010). After intra-articular injection of CS, the reduction in pain was greatest 6 weeks after administration, and the mean value was the lowest among all groups. During subsequent visits, the value of the pain subscale increased, and after 6 months, it was the highest among the studied groups. Using the Wilcoxon paired test, no PRP effect was found to reduce stiffness at the 6-month follow-up (p = 0.908). Functional improvement was achieved in all groups, i.e., a decrease in the value of this subscale 6 months after administration. The largest decrease was seen in the group that received PRP (p < 0.001) and then in the HA group. The smallest decrease among the investigated methods was shown in the CS group. Conclusions: Intra-articular injections of PRP can provide clinically significant functional improvement for at least 6 months in patients with mild to moderate KOA which is superior to HA or CS injections.
MAXIMISE (Managing AXIal Manifestations in psorIatic arthritis with SEcukinumab) trial was designed to evaluate the efficacy of secukinumab in the management of axial manifestations of psoriatic arthritis (PsA).This phase 3b, double-blind, placebo-controlled, multi-centre 52-week trial included patients (≥18 years) diagnosed with PsA and classified by ClASsification criteria for Psoriatic Arthritis (CASPAR) criteria, with spinal pain Visual Analogue Score ≥40/100 and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥4 despite use of at least two non-steroidal anti-inflammatory drugs (NSAIDs). Patients were randomised (1:1:1) to secukinumab 300 mg, secukinumab 150 mg or placebo weekly for 4 weeks and every 4 weeks thereafter. At week 12, placebo patients were re-randomised to secukinumab 300/150 mg. Primary endpoint was ASAS20 (Assessment of SpondyloArthritis international Society) response with secukinumab 300 mg at week 12.Patients were randomly assigned; 167 to secukinumab 300 mg, 165 to secukinumab 150 mg and 166 to placebo. Secukinumab 300 mg and 150 mg significantly improved ASAS20 response versus placebo at week 12 (63% and 66% vs 31% placebo). The OR (95% CI) comparing secukinumab 300 mg and 150 mg versus placebo, using a logistic regression model after multiple imputation, was 3.8 (2.4 and 6.1) and 4.4 (2.7 and 7.0; p<0.0001).Secukinumab 300 mg and 150 mg provided significant improvement in signs and symptoms of axial disease compared with placebo in patients with PsA and axial manifestations with inadequate response to NSAIDs.NCT02721966.
Involvement of the non-classical human leucocyte antigen-E (HLA-E) in both innate and acquired immune response suggests its possible role in development of autoimmune pathologies. This study was undertaken to investigate relationships between the HLA-E gene single nucleotide polymorphisms (SNPs) and a risk of rheumatoid arthritis (RA), as well as to evaluate a potential of these polymorphisms to modulate clinical outcome of anti-tumour necrosis factor (TNF) treatment in female patients. A total of 223 female patients with RA receiving anti-TNF biological therapy and 134 female healthy subjects were enrolled into the study. Genotypings for two SNPs within the HLA-E gene (rs1264457 HLA-E*01:01/01:03; rs1059510 HLA-E*01:03:01/01:03:02) were performed using a polymerase chain reaction (PCR) amplification employing LightSNiP assays. Clinical response was evaluated according to the European League Against Rheumatism (EULAR) criteria at 12 and 24 weeks after initiation of the therapy. The frequency of the HLA-E*01:01/01:01 genotype was decreased significantly in RA patients in comparison to controls (P = 0.031). The presence of the HLA-E*01:01/01:01 genotype in patients correlated with better EULAR response after 12 weeks of anti-TNF treatment, while 01:03 allele carriers were generally unresponsive to the treatment (P = 0.014). The HLA-E*01:03/01:03 genotype was also over-represented among non-responding patients in comparison to HLA-E*01:01/01:01 homozygotes (P = 0.021). With respect to the HLA-E rs1059510 variation, a better response after 12 weeks was observed more frequently in patients carrying the HLA-E*01:03:01/01:03:01 genotype than other genotypes (P = 0.009). The results derived from this study imply that HLA-E polymorphisms may influence RA susceptibility and affect clinical outcome of anti-TNF therapy in female RA patients.
Abstract Inconsistency of the results regarding the genetic variability within genes coding for receptor activator of nuclear factor κB (RANK) and its ligand (RANKL) in rheumatoid arthritis (RA) prompted us to study the RANK and RANKL polymorphisms as potential biomarkers associated with disease predisposition and response to anti-TNF treatment in a group of Polish patients with RA. This study enrolled 318 RA patients and 163 controls. RANK (rs8086340, C > G; rs1805034, C > T) and RANKL (rs7325635, G > A; rs7988338 G > A) alleles were determined by real-time PCR with melting curve analysis and related with clinical parameters. In addition, RANKL serum levels were measured by ELISA. The RANK rs8086340- G allele was overrepresented among patients as compared to controls (OD = 1.777, p = 0.038). C-reactive protein (CRP) levels were significantly ( p < 0.05) associated with RANK rs8086340 polymorphism and were higher in the CC -homozygotes at the baseline while lower in the GG -carriers at the 12th week of the treatment. At the latter time point RANKL rs7325635- GG- positive patients also showed significantly lower CRP concentrations. Higher alkaline phosphatase levels before induction of anti-TNF therapy were observed in RANK rs8086340 and RANK rs1805034 CC homozygotes ( p = 0.057 and p = 0.035, respectively). The GG homozygosity of both RANKL single nucleotide polymorphisms was significantly associated with the number of swollen joints (rs7988338 and rs7325635, before and at the 12th week of therapy, respectively, p < 0.05 in both cases). These results imply that polymorphisms within the RANK and RANKL genes affect RA susceptibility and anti-TNF treatment outcome.
Exposure to heavy metals and lifestyle factors like smoking contribute to the production of free oxygen radicals. This fact, combined with a lowered total antioxidant status, can induce even more damage in the development of ankylosing spondylitis (AS). Despite the fact that some researchers are looking for more genetic factors underlying AS, most studies focus on polymorphisms within the genes encoding the human leukocyte antigen (HLA) system. The biggest challenge is finding the effective treatment of the disease. Genetic factors and the influence of oxidative stress, mineral metabolism disorders, microbiota, and tobacco smoking seem to be of great importance for the development of AS. The data contained in this review constitute valuable information and encourage the initiation and development of research in this area, showing connections between inflammatory disorders leading to the pathogenesis of AS and selected environmental and genetic factors.
To evaluate fenebrutinib, an oral and highly selective non-covalent inhibitor of Bruton's tyrosine kinase (BTK), in patients with active rheumatoid arthritis (RA).
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