AB0565 JAK INHIBITORS AND PSORIATIC ARTHRITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Background:Despite the therapeutic armamentarium for the treatment of psoriatic arthritis (PsA) has considerably expanded over the last thirty years, there is a huge necessity of finding effective drugs for this disease. JAK inhibitors (JAKi) are small molecules able to interfere with the JAK/STAT pathway, involved in the pathogenesis of PsA (1). Up to now Tofacitinib is the only JAKi approved by the European Medicines Agency (EMA) for the treatment of PsA but in the next few years the number of approved JAKi is expected to rise significantly.Objectives:To assess the efficacy and safety of different JAKi for the treatment of PsA.Methods:A systematic review of the literature was performed to identify randomized controlled trials (RCTs), by electronic search of MEDLINE and EMBASE database until October 2020. Studies were considered eligible if they met the following criteria: I) study was a RCT; II) only patients with PsA were included; III) JAKi was compared to placebo in addition to the standard of care. Two reviewers (FC and AZ) performed study selection, with disagreements solved by the opinion of an expert reviewer (AS). The outcomes were expressed as odds ratio (OR) and 95% confidence intervals (95% CI). Statistical heterogeneity was assessed with the I2 statistic.Results:We identified 557 potentially relevant studies. A total of 554 studies were excluded based on title and/or abstract screening. Three RCTs for a total of 947 PsA patients treated with JAKi were included (2,3,4). Two were phase III studies on the efficacy and safety of Tofacitinib (OPAL Beyond and OPAL Broaden) and one was a phase II study on Filgotinib (Equator). All three studies were judged at low risk of bias according to Cochrane criteria (5). The primary efficacy outcome in all the studies was the number of patients who achieved the response rate of the American College of Rheumatology 20 score (ACR20). The outcomes evaluation was performed at 12 week for the Filgotinib trial and at 16 week for the Tofacitinib trials. We used for the main analyses the group of patients randomized to Tofacitinib 5 mg because this is the only dosage approved by the EMA for the treatment of PsA. JAKi showed a significantly higher ACR20 response rate compared to placebo (OR 3.54, 95% CI 1.76 - 7.09, I^2 = 74%). JAKi also showed a significantly higher ACR50 response rate (OR 3.36, 95% CI 2.22 - 5.09, I^2 = 0%), ACR70 response rate (OR 2.82, 95% CI 1.67 - 4.76, I^2 = 20%), PsARC response rate (OR 2.67, 95% CI 1.26 - 5.65, I^2 = 79%), PASI75 response rate (OR 3.15, 95% CI 1.61 - 6.15, I^2 = 45%) compared to placebo. JAKi were also associated with significantly better HAQ-DI (mean difference -0.23 95% CI -0.31 - -0.14) and fatigue, measured with FACIT-F (mean difference 3.54 95% CI 2.13 - 4.94). JAKi compared to placebo were associated with a non-statistically significant different risk of serious adverse events (OR 0.56, 95% CI 0.11 - 2.91, I^2 = 38%).Conclusion:This is the first published systematic review that performed a comprehensive and simultaneous evaluation of the efficacy and safety of JAKi for PsA in RCTs. Our analysis suggests a statistically significant benefit of JAKi, that appears to be effective and safe over placebo. The impact of these data on international clinical guidelines needs further investigation.References:[1]George E Fragoulis, et al. JAK-inhibitors. New players in the field of immune-mediated diseases, beyond rheumatoid arthritis, Rheumatology, Volume 58, Issue Supplement_1, February 2019, Pages i43–i54[2]Mease P, et al. Tofacitinib or adalimumab versus placebo for psoriatic arthritis. N Engl J Med 2017; 377: 1537-50.[3]Gladman D, et al. Tofacitinib for psoriatic arthritis in patients with an inadequate response to TNF inhibitors. N Engl J Med 2017; 377: 1525-36.[4]Mease P, et al. Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active psoriatic arthritis (EQUATOR): results from a randomised, placebo-controlled, phase 2 trial. Lancet 2018;392:2367–77.[5]Higgins JP, et Al. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-560Figure 1.ACR20 response rate of Jaki over PlaceboDisclosure of Interests:None declared

THU0454 SOMATIC SYMPTOMS IN FIBROMYALGIA AND THEIR CORRELATION WITH DRUG TREATMENT

Background:Drug treatment in fibromyalgia (FM) is often disappointingly ineffective, and there are currently very few data to support therapeutic choices towards a personalized medicine approach.Objectives:To evaluate the prevalence of selected somatic symptoms in FM, and to study their relationship with drug treatments.Methods:The study population consisted of 526 patients (471 F 55 M, mean age 47.31±11.33 yrs) affected by FM not associated with other rheumatic diseases. All patients were required to compile a questionnaire reporting the presence of 42 somatic symptoms -as suggested (1) – in the last 7 days. Drug usage was assessed by interview.Results:On average, patients reported the presence of 17.04±6.68 symptoms (range 4-35), with ample variations in the prevalence of different symptoms (Fig. 1), ranging from over 95% (fatigue and muscle pain) to less than 10 %, seizures being reported by only 2 patients (0.4%). 31.1% of patients were not taking any drug for their FM. The most frequently used drugs were analgesics (ANA, 41.7%) followed by benzodiazepines (BD, 29.1%), SSRIs (16%), gabapentinoids (GABA, 14,4%), and NSRI (14.3%) (Fig. 2). Different drugs were associated with a different spectrum of somatic symptoms: as compared to non users, BD users reported a significantly higher (p< 0.05 by chi-square test) prevalence of irritable bowel (65.4% vs 52.3%), fatigue (98.7% vs 94.9%), thinking difficulties (78.4% vs 68.5%), muscle weakness (94.1% vs 81.7%), abdominal pain (55.6% vs 43.9%), insomnia (73.9% vs 56.6%), depression (63.4 % vs 37.2%), constipation (60.1% vs 42.9%), pain in upper abdomen (50.3% vs 40.2%), nausea (53.6% vs 38.3%), nervousness (71.9% vs 61.5%), chest pain (49.0 vs 37.75), blurred vision (65.4% vs 53.6%), dry mouth (72.5% vs 52.3%), itching (56.2% vs 44.5%), vomiting (13.7% vs 7.8%), taste change (22.2% vs 12.7%), dry eyes (55.6% vs 41.0%), breath shortness (56.9% vs 47.7%), appetite loss (33.3% vs 19.7%), painful urination (15.0% vs 8.4%), and bladder spasms (18.3% vs 8.6%). NRSI users reported a significantly higher prevalence of thinking difficulties, constipation, blurred vision, dry mouth, wheezing, dry eyes, easy bruising. Among GABA users, there was a higher prevalence of thinking difficulties, numbness, insomnia, constipation, nausea, dry mouth, dry eyes, appetite loss, sun sensitivity, easy bruising, and bladder spasms. In no cases a higher prevalence of symptoms was recorded in drug non users vs users.Conclusion:The usage of different drugs in FM is associated with different somatic symptoms. The higher prevalence of symptoms in drug users as compared to non users raises serious questions concerning the opportunity or the appropriateness of drug selection in FM.References:[1]Wolfe F., et al. Arthritis Care Res (Hoboken). 2010 May;62(5):600-10Disclosure of Interests: :None declare