Background: Methotrexate (MTX) is one of the most common medications used for rheumatoid arthritis (RA) treatment. Single-nucleotide polymorphisms (SNPs) could potentially predict variability in therapeutic outcomes. Aim: This study aims to assess the impact of SNPs in genes encoding for the MTX pathway for predicting clinical and therapeutic responses to MTX in a cohort of Egyptian patients with RA. Subjects and Methods: Data from 107 Egyptian RA patients (aged 44.4 ± 11.4 years) treated with MTX monotherapy, for a duration of 3.7 ± 3.3 years, were collected. Genotypes of 10 SNPs from four different genes were analyzed using the allelic discrimination PCR technique. Results: The ATIC rs3821353 G/T (p = 0.034) and the C/T and C/C of SLC19A1 rs7279445 (p = 0.0018) were associated with a non-response to MTX, while DHFR rs10072026 C/T and C/C were associated with a good response (p < 0.001). Carriers of the ATIC rs382135 3 G (p = 0.001) and ATIC rs4673990 G (p < 0.001) alleles were more likely to develop RA, while the SLC19A1 rs11702425 T (p < 0.001) and GGH rs12681874 T (p = 0.003) allele carriers were more likely to be protected against RA. Carriers of the ATIC rs4673990 A/G genotype (p < 0.001) were at risk of developing RA, while carriers of the following genotypes were mostly protected against RA: ATIC rs3821353 T/T (p < 0.001), ATIC rs3821353 G/G (p = 0.004), SLC19A1 rs11702425 T/T (p = 0.001), SLC19A1 rs11702425 C/T (p = 0.003), GGH rs12681874 C/T (p = 0.004) and GGH rs12681874 T/T (0.002). Conclusion: The genotyping of genes involved in the MTX pathway may be helpful to predict which RA patients will/will not benefit from MTX, and thus, may help to apply a personalized medicine approach in RA.

Background Pain in osteoarthritis (OA) has been attributed traditionally to local tissue injury causing ‘nociceptive pain’. However, recent studies suggest that neuropathic and central sensitization mechanisms may contribute to the pain experience. However, the relationship between these pain mechanisms and physical function has not been thoroughly addressed. This study aimed to assess the association of central sensitization and neuropathic pain with physical function in knee OA. Results Participants with a positive central sensitization inventory score (CSI) (≥ 40) had a decreased total Knee injury and Osteoarthritis Outcome Score (KOOS) and its subscales (p < 0.001), a longer timed up and go test time (p = 0.002) and a higher PainDETECT questionnaire (PD-Q) and visual analogue scale (p < 0.001, p = 0.026 respectively). The severity of Kellgren-Lawrence grading (KL) (p < 0.001), depressive and anxiety symptoms (p < 0.001) increased with neuropathic pain severity. In addition, participants with a high PD-Q score (≥ 19) had a longer timed up and go test time (p < 0.001) and a decreased total KOOS score (p < 0.001). Moreover, we found that CSI score, KOOS score, and KL grading were significantly predicted the PD-Q score (p = 0.046, p < 0.001, p = 0.007, respectively). Regarding the physical function predictors, multivariate linear regression analysis revealed that pressure pain threshold at right elbow and right knee (p = 0.005, p < 0.001) in addition to PD-Q (P < 0.001) were significantly associated with KOOS score, while CSI and Hospital Anxiety Depression Scale were not. Conclusion Knee OA patients with significant central sensitization and neuropathic pain reported increased pain, more functional impairment, more anxiety and depressive symptoms than OA patients without central sensitization and neuropathic pain. Additionally, neuropathic pain and presence of central sensitization were significant predictors for functional ability.

BackgroundWe no longer consider Osteoarthritis (OA) as a degenerative disease, but rather as a multifactorial disorder in which low grade, chronic inflammation has a central role. In addition, evidence points to the presence of both peripheral and central nervous system sensitization as sources of pain in OA. Transcutaneous Vagus Nerve Stimulation (tVNS) has shown efficacy on pain, inflammation and central sensitization in other conditions such as fibromyalgia, pelvic pain, and headaches and therefore we hypothesized that tVNS could be an additional line of management for knee OA.ObjectivesTo assess the efficacy and safety of tVNS on nociceptive pain, central sensitization, neuropathic pain, depression, anxiety, and physical function in individuals with knee OA.MethodsAfferents of the auricular branch of vagus nerve were stimulated using an auricular electrode connected to a transcutaneous electrical nerve stimulation (TENS) device. We conducted 30 minutes session once a day for 3 days per week for 12 weeks. Sixty-eight patients with chronic knee OA were allocated randomly into active and sham group (34 patients in each group). The outcome measures included visual analogue scale (VAS), pressure pain threshold (PPT), PainDETECT and Douleur Neuropathique 4 (DN4) questionnaires, hospital anxiety and depression scale (HADS), and knee injury and osteoarthritis outcome score (KOOS). These outcome measures were assessed at baseline, at the end of the stimulation period then after 4 weeks later.ResultsThere was a significant improvement in VAS for pain score in the active tVNS group between the baseline and first follow-up visit, and between the baseline and second follow-up visit (P <0.001). The median VAS improvement was 4.0 (3.0 – 5.0) in active group versus 1.0 (1.0 – 2.0) in sham group (p <0.001). PPT in right knee, left knee and right elbow was significantly improved compared to baseline in active tVNS and maintained till 4-weeks post-intervention. On the other hand, in the sham group tVNS, right knee PPT was improved but not maintained. PainDETECT and DN4 questionnaires were statistically improved in active tVNS (p <0.001). In contrast, DN4 questionnaire showed no improvement at all and PainDETECT showed improvement that was not maintained at the end of follow up in sham group. A statistically significant improvement in HADS immediately post intervention in active and sham tVNS (p <0.001), this improvement was maintained only in the active group 4 weeks after intervention. Regarding functional outcomes, the improvement in KOOS was significant in the active group only (31.44 ± 18.49, p > 0.001). No serious adverse events were reported in both study groups.ConclusionThis study provides preliminary evidence for the beneficial effects of tVNS in OA and raises the possibility of using neuromodulation as an add-on treatment to existing pharmacological and non-pharmacological measures.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.