Few studies compared adalimumab to other targeted therapies in head-to-head randomized clinical trials (RCTs) for rheumatoid arthritis (RA), but multiple comparisons are not available. This Bayesian Network Meta-Analysis evaluated which targeted therapy is more likely to achieve ACR50 response with good safety at 24 weeks of treatment in RA. A systematic literature review was conducted for head-to-head phase 3 RCTs that compared adalimumab to other targeted therapies in combination with methotrexate (MTX) or as monotherapy to treat RA patients, and searched through MEDLINE, EMBASE, Cochrane Library and Clinicaltrial.gov. The outcomes of interest were ACR50 response and withdrawals due to adverse events at 24 weeks. WinBUGS 1.4 software (MRC Biostatistics Unit, Cambridge, UK) was used to perform the analyses, using a random effect model. Sixteen studies were included in the analysis. The most favorable SUCRA for the ACR50 response rate at 24 weeks of treatment in combination with MTX was ranked by upadacitinib, followed by baricitinib, tofacitinib and filgotinib. As monotherapy, the highest probability was ranked by tocilizumab followed by sarilumab. No significant differences in safety profile among treatment options were found. Jak-inhibitors in combination with MTX and interleukin-6 antagonism as monotherapy showed the highest probability to achieve ACR50 response after 24 weeks of treatment. None of assessed targeted therapies were associated to risk of withdrawal due to adverse events. Key messages: Direct and indirect comparison between adalimumab and other targeted therapies demonstrated some differences in terms of efficacy that may help to drive RA treatment. Jak-inhibitors and interleukine-6 antagonists ranked as first in the probability to achieve ACR50 response after 24 weeks of treatment in combination with methotrexate or monotherapy, respectively.

Introduction:The objective of this study was to assess the 10-year prevalence of latent tuberculosis infection (LTBI) among Apulian patients with rheumatic diseases (RDs). Secondary endpoint was to record new cases of active TB disease and LTBI among patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs). Methods: We analysed the results from the patients included in the BIOPURE registry from 2009 to 2018, who underwent QuantiFERON-TB Gold In-tube (QFT-GIT) test as screening before bDMARDs treatment. Demographic and clinical data were recorded at the time of the first QFT-GIT test. Administration of preventive therapy and bDMARD treatments were recorded for patients with positive QFT-GIT test. All new tuberculosis infections were recorded during the follow-up. Results:The final study population included 3028 patients (855 rheumatoid arthritis, 1001 psoriatic arthritis, 833 spondyloarthritis, 130 connective tissue diseases, 33 systemic vasculitis and 176 other inflammatory rheumatic conditions), more frequently female (67.2%), with a mean age of 52 ± 18 years. Patients with QFT-GIT-positive test were elderly people, predominantly male with higher prevalence of diabetes as comorbidity. The 10-year prevalence of LTBI was 10.8%. Of note, no cases of TB reactivation were recorded in patients who completed preventive therapy treatment. Three thousand and sixteen patients were followed over time (42.6 ± 30 months), and five (.2%) developed active TB, which corresponds to .47 cases per 1000 person-years. Conclusions:In the 10-year observation, the use of bDMARDs seems to be safe in rheumatologic patients with positive QFT-GIT test treated according to current

Review question / Objective: To indentify which targeted therapy is more likely to achieve the 50% American College of Rheumatology (ACR50) response with good safety at 24-weeks of treatment in rheumatoid arthritis (RA) patients. Rationale: Head to head RCTs that compared biologic (b)-and targeted syntethic (ts)-DMARDs are limited to few studies and the best agents for RA treatment is unknown. Condition being studied: Head-to-head phase 3 RCTs that compared adalimumab to other targeted therapies in combination INPLASY 1

Background:Biologic agents and small molecules have shown long term benefit when added in patients with active RA non-responders to conventional DMARDs treatment (1). In head-to-head trials only adalimumab was compared to other drugs in combination with methotrexate, with some evidence of superiority but no data on multiple comparisons have been reported (2). The availability of biosimilar agents led in clinical practice to prefer mainly the cheaper one, so the choice of the most effective treatment remains a clinical unmet need (3).Objectives:To assess the relative efficacy of different therapeutic strategies for achieving ACR50 response at 24 weeks of treatment in patients with active RA, based on direct and indirect evidence.Methods:We performed systematic reviews of MEDLINE, EMBASE, and Cochrane Library databases, searching for all published phase 3 Randomised Controlled Trials (RCTs) comparing adalimumab originator to its biosimilars, abatacept, baricitinib, certolizumab pegol, tofacitinib or upadacitinib, combined to MTX, in patients with active RA inadequate responders to previous conventional DMARDs. American College of Rheumatology (ACR) 50% response at 24 weeks of treatment had to be evaluated both in adalimumab branch and in examined drug branch. Bayesian fixed-effect network meta-analysis was performed to combine the direct and indirect evidence using the WinBUGS 1.4 software (MRC Biostatistics Unit, Cambridge, UK).Results:Eleven RCTs evaluating 6’004 patients were included in the analysis, namely originator (1) and biosimilars (2) adalimumab, abatacept (3), baricitinib (4), certolizumab pegol (5), tofacitinib (6) and upadacitinib (7). Convergence was reached at n.100’000 iterations. Upadacitinib seems to be more effective than both originator and biosimilar adalimumab in achieving ACR 50 (OR 1.65 95% CI 1.25-2.14 and OR 1.22 95%CI 1.10-2.18; see Figure 1). Similarly, tofacitinib was more effective of originator adalimumab (OR 1.25 95%CI 1.01-155). Upadacitinib was ranked first among treatments with a probability of being the agent more likely to induce ACR 50 response of 86.3%. In this regard tofacitinib had a probability of 4.8%, hence it was ranked second among treatments.Figure 1.Caterpillar plot OR for ACR50 at 24 weeks (originator [1] and biosimilars [2] adalimumab; abatacept [3]; baricitinib [4]; certolizumab pegol [5]; tofacitinib [6]; upadacitinib [7]).Conclusion:Although patients with active RA and inadequate response to MTX have different therapeutic combination of biologics or small molecules options, the best relative efficacy in terms of ACR50 response after 24 weeks of treatment is for upadacitinib 15 mg/day.References:[1]Smolen JS, et al. Annals of the Rheumatic Diseases 2020;79:685-699.[2]Combe B, Lukas C. Joint Bone Spine, 2020,105004.[3]Caporali R, et al. Biomed Res Int. 2018 Sep 9;2018:3878953.Disclosure of Interests:Fabio Cacciapaglia Speakers bureau: Roche, Pfizer, Eli Lilly, MSD, UCB, BMS, Abbvie, Vincenzo Venerito: None declared, Stefano Stano: None declared, Marco Fornaro: None declared, Giuseppe Lopalco Speakers bureau: Celgene, BMS, Abbvie, Novartis, Florenzo Iannone Speakers bureau: Roche, Pfizer, Eli Lilly, MSD, UCB, BMS, Abbvie, Novartis, Celgene

The use of immunoglobulin is a therapeutic option with increasing evidence of efficacy for different rheumatologic autoimmune systemic diseases. Some studies concerning immunoglobulin use in systemic sclerosis have been published with encouraging results. We present the case of a young woman diagnosed with rapidly progressive diffuse cutaneous systemic sclerosis, refractory to therapy with methotrexate and rituximab, which presented a relevant skin improvement after one year of subcutaneous immunoglobulin (2 g/kg cumulative monthly dose, refracted in weekly administrations). Furthermore, a narrative literature review of the evidence for alternative treatments with a focus on immunoglobulin use for systemic sclerosis skin involvement was carried out.