Effectiveness of sequential lines of biologic and targeted small-molecule drugs in psoriatic arthritis: a systematic review.

OBJECTIVE: To assess current evidence for effectiveness of sequential lines of biologic and targeted small-molecule disease-modifying anti-rheumatic drugs (b/tsDMARDs) when used beyond first-line for psoriatic arthritis (PsA). METHODS: A systematic search of the literature (Medline, Embase, bibliographic searches) was undertaken (October and December 2022) to find studies meeting the criteria of assessing effectiveness of b/tsDMARDs beyond first-line in adults with PsA (PROSPERO CRD42022365298). Risk of bias assessment was undertaken (ROBINS-I/Cochrane RoB2). RESULTS: Of 2666 abstracts identified and following a full text review of 177 psoriatic disease studies, 12 manuscripts and two abstracts were eligible. Of the 12 manuscripts, 11 were observational and one was a sub-analysis of a RCT (n = 16 081: average age 49.5 years, female 53.3%). Two abstracts (n = 7186) were included. All studies comparing first- and second-line (three studies) found a reduced response in second-line. On average, DAPSA remission (most reported outcome, eight studies) was achieved in 26%, 19% and 10% first-, second- and third-line TNFi, and 22%, 13% and 11% first-, second- and third-line other bDMARDs, respectively. Responses varied to third-line bDMARDs; four studies found comparable second- and third-line responses, five studies found diminishing responses in sequential lines. CONCLUSION: Predominantly observational studies, inherently at high risk of bias, indicate bDMARDs can be effective to third-line in PsA, but that response is reduced after first line. There is very limited data for more advanced lines of b/tsDMARD. Prospective studies are required to better understand clinical response to advanced lines of treatment in PsA.

Impact of body composition on clinical outcomes in patients with active radiographic axial spondyloarthritis under biological therapy.

OBJECTIVE: To assess the association of body composition, evaluated by bioimpedance analysis (BIA), with disease activity, physical function, and mobility in patients with axSpA undergoing bDMARD treatment for one year. METHODS: Patients with AS (radiographic axSpA) were enrolled in an extension of the German Spondyloarthritis Inception Cohort (GESPIC). Patients were required to be candidates for bDMARD therapy at baseline presenting high disease activity despite previous treatment with nonsteroidal anti-inflammatory drugs. Outcomes (disease activity, function, and mobility) and body composition parameters were assessed at baseline and every 6 months thereafter. Body composition was assessed by BIA. The association between body composition parameters and outcomes over 1 year was analyzed using longitudinal generalized estimating equations. RESULTS: Seventy-four patients with radiographic axSpA were included in current analysis with a mean age of 36.5 years, disease duration of 6.2 years and ASDAS-CRP score of 3.4 at baseline. Fat mass value and fat mass index were positively associated with disease activity (ASDAS: ß = 0.01, 95% CI [-0.01, 0.03] and ß = 0.04, 95% CI [-0.01, 0.08], respectively) and functional disability (BASFI). Visceral adipose tissue (VAT) was associated with reduced spine mobility (BASMI: ß = 0.20, 95% CI [0.07, 0.33]). Additionally, increase in VAT and fat mass parameters was linked to worse disease activity and functional disability in women, while they were strongly associated with reduced spinal mobility in men. CONCLUSIONS: Higher levels of body fat and VAT were positively associated with increased disease activity, functional disability, and reduced spinal mobility in patients with radiographic axSpA treated with bDMARDs.

[Head-to-head studies on psoriasis and psoriatic arthritis]. / Head-to-Head-Studien bei Psoriasis und Psoriasisarthritis.

Given the ever-increasing number of approved therapies for the treatment of psoriasis (PsO) and psoriatic arthritis (PsA), head-to-head (H2H) comparative studies are essential. These are aimed primarily at a comparative analysis of treatment effectiveness. In both PsO and PsA, biological disease-modifying antirheumatic drugs (bDMARD) have been shown to be superior to conventional therapies in H2H studies. In PsO interleukin 17 (IL-17) and IL-23 inhibitors proved superiority compared to tumor necrosis factor (TNF) inhibitors (etanercept and adalimumab) in several studies. Ustekinumab was more effective than etanercept, but less effective than IL-17 and IL-23 inhibitors. Only a few H2H studies have been published on the treatment of PsA. In the Spirit H2H study ixekizumab was superior to adalimumab using a combined endpoint of arthritis and psoriasis response (ACR-50 and PASI-100). When looking at arthritic symptoms only (ACR-20), secukinumab was not significantly superior to adalimumab in the EXCEED study but was superior in terms of the effect on skin involvement (PASI90). Other H2H studies focused on the treatment of enthesitis (ECLIPSA study), the efficacy of Janus kinase (JAK) inhibition (SELECT-PSA-1) or the additional administration of methotrexate to bDMARD treatment (MUST study). The H2H data have been incorporated into the treatment guidelines and have led to IL-17 and IL-23 inhibition being preferred over TNF inhibition in cases of relevant skin involvement in PsA.

Therapeutic consequences in patients with both inflammatory rheumatic diseases and multiple sclerosis.

Dealing with patients with both multiple sclerosis (MS) and inflammatory rheumatic disorders (IRDs) is not uncommon for a rheumatologist, as there is a statistical association between SpA and MS. As several CNS demyelinating events have been reported in patients treated with TNF inhibitor (TNFi), the pre-existing demyelinating disease was considered a contraindication for TNFi. However, this contraindication is mainly based on a randomized controlled trial in MS and not on large epidemiological studies. According to the last epidemiological studies, TNFi might not be an inducer of MS. Moreover, there are no clear recommendations on the use of the other DMARDs in patients suffering from an IRD and MS. In this review, we summarize the link between MS and IRDs and the impact of DMARDs on MS, especially TNFi. We also look at the impact of disease-modifying drugs for adults with MS and IRDs.

Impact of initial therapy with upadacitinib or adalimumab on achievement of 48-week treatment goals in patients with rheumatoid arthritis: post hoc analysis of SELECT-COMPARE.

OBJECTIVES: Evaluate the importance of treatment sequencing in SELECT-COMPARE, assessing potential differences between starting upadacitinib or adalimumab therapy following inadequate MTX response. METHODS: Patients from SELECT-COMPARE were randomized to upadacitinib 15 mg once daily, placebo or adalimumab 40 mg. Per protocol, patients with <20% improvement in tender or swollen joint counts (weeks 14, 18, 22) or failure to achieve Clinical Disease Activity Index (CDAI) low disease activity (LDA) at week 26 were blindly switched from upadacitinib to adalimumab or vice versa. Treatment outcomes, including clinical remission/LDA, physical function, pain and a novel combined endpoint for deep response, were evaluated through 48 weeks and corresponding time-averaged response rates determined. Data were analysed by initial randomized group regardless of any subsequent switch in therapy. RESULTS: This post hoc analysis included 651 patients initially randomized to upadacitinib (of whom 252 switched to adalimumab) and 327 patients initially randomized to adalimumab (of whom 159 switched to upadacitinib). At week 48, patients randomized to either therapy demonstrated similar achievement of most treatment endpoints. Greater improvements in the total time spent in a lower disease state were observed for initial upadacitinib vs initial adalimumab therapy across most clinical and patient-reported outcomes through 48 weeks, and the median time to DAS28(CRP) <2.6/≤3.2 occurred 6-8 weeks earlier among those randomized to upadacitinib. CONCLUSION: Following a modified treat-to-target strategy, rates of CDAI remission/LDA and DAS28(CRP) <2.6/≤3.2 at 48 weeks were similar, regardless of starting therapy. However, patients initially receiving upadacitinib reached treatment targets more quickly and spent more time in clinical targets over the initial 48 weeks of treatment. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02629159.

Gender-specific differences in patients with psoriatic arthritis receiving ustekinumab or tumour necrosis factor inhibitor: real-world data.

OBJECTIVE: Investigate effects of gender on disease characteristics and treatment impact in patients with PsA. METHODS: PsABio is a non-interventional European study in patients with PsA starting a biological DMARD [bDMARD; ustekinumab or TNF inhibitor (TNFi)]. This post-hoc analysis compared persistence, disease activity, patient-reported outcomes and safety between male and female patients at baseline and 6 and 12 months of treatment. RESULTS: At baseline, disease duration was 6.7 and 6.9 years for 512 females and 417 males respectively. Mean (95% CI) scores for females vs males were: clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA), 32.3 (30.3, 34.2) vs 26.8 (24.8, 28.9); HAQ-Disability Index (HAQ-DI), 1.3 (1.2, 1.4) vs 0.93 (0.86, 0.99); total PsA Impact of Disease-12 (PsAID-12) score, 6.0 (5.8, 6.2) vs 5.1 (4.9, 5.3), respectively. Improvements in scores were smaller in female than male patients. At 12 months, 175/303 (57.8%) female and 212/264 (80.3%) male patients achieved cDAPSA low disease activity, 96/285 (33.7%) and 137/247 (55.5%), achieved minimal disease activity (MDA), respectively. HAQ-DI scores were 0.85 (0.77, 0.92) vs 0.50 (0.43, 0.56), PsAID-12 scores 3.5 (3.3, 3.8) vs 2.4 (2.2, 2.6), respectively. Treatment persistence was lower in females than males (P ≤ 0.001). Lack of effectiveness was the predominant reason to stop, irrespective of gender and bDMARD. CONCLUSIONS: Before starting bDMARDs, females had more severe disease than males and a lower percentage reached favourable disease states, with lower persistence of treatment after 12 months. A better understanding of the mechanisms underlying these differences may improve therapeutic management in females with PsA. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02627768.

Biological disease-modifying anti-rheumatic drugs are equally effective in psoriatic arthritis patients with low and high joint counts.

OBJECTIVE: A lack of representation in pivotal trials currently limits guidance for the use of biological disease-modifying anti-rheumatic drugs (bDMARDs) in psoriatic arthritis (PsA) patients with a low number of actively inflamed joints. The aim of this study was to compare the effectiveness of a first bDMARD in PsA patients with low vs high number of affected joints. METHODS: PsA patients with available 66/68 joint count assessments were divided into low joint count (LJC) patients when presenting with <3 tender or < 3 swollen joints or high joint count patients (HJC) with > =3 joints in both categories. We studied drug retention as a joint count independent effectiveness variable in LJC and HJC patients in univariate and multivariable adjusted Cox regression models. RESULTS: 197 LJC patients differed not only in joint counts, but also had lower enthesitis scores, less often dactylitis, less disability and a better health related quality of life at first bDMARD initiation than 190 HJC patients. However, LJC were less often on conventional synthetic (cs) DMARDs. Despite these differences at baseline, bDMARD retention was not significantly different between LJC and HJC in both crude and adjusted analyses (Hazard Ratio (HR) 1.09 [0.76-1.58], p= 0.52). Furthermore, bDMARD retention was significantly better (HR 0.63 [0.47-0.85], p< 0.002) when administered with csDMARD co-therapy. CONCLUSIONS: Biological DMARDs were similarly effective in terms of drug retention in patients with low and high joint counts. In the setting of absent remission and a significant disease burden, bDMARDs should not be withheld from patients because they exhibit only a low joint count.

[Methotrexate treatment before use of biologics in rheumatoid arthritis : Analysis of guideline compliance]. / Methotrexat-Versorgung vor dem Einsatz von Biologika bei rheumatoider Arthritis : Eine Analyse der Leitliniengerechtigkeit.

BACKGROUND: With the introduction of biologics the treatment landscape for patients with rheumatoid arthritis (RA) has rapidly expanded; however, according to German and European treatment guidelines the use of biologic disease-modifying antirheumatic drugs (bDMARD) is only indicated after insufficient response under methotrexate (MTX) doses of at least 20 mg/week (first-line treatment). The aim of the study was to analyze the guideline compliance of MTX prescription in the outpatient sector prior to treatment with biologics. MATERIAL AND METHODS: Claims data from the AOK Lower Saxony from 2013 to 2016 were provided for all insured patients with a diagnosis of RA and bDMARD prescription during the study period. Within a patient-specific observational period of 180 days prior to the first bDMARD prescription, the maximum prescribed MTX dosage was examined. RESULTS: Data from 90 incident and 315 prevalent RA patients were analyzed. A maximum MTX prescription of < 20 mg/week was observed in 60.0% of incident patients and in 67.0% of prevalent patients. Men had a higher mean MTX maximum dose (17.1 ± 4.8 mg) than women (14.9 ± 5.0 mg; p < 0.0001). Of the study population 29.6% received oral only prescriptions during the observational period. In 12.4% of patients a switch to parenteral administration was made. DISCUSSION: Targeted use of the full spectrum of therapies provided prior to initiation of bDMARD treatment may contribute to cost-effective RA care. This study showed indications for potential deficits in outpatient MTX prescription practice and can raise awareness for efficient treatment.

Pregnancy outcomes in relation to disease activity and anti-rheumatic treatment strategies in women with rheumatoid arthritis: a matched cohort study from Sweden and Denmark.

OBJECTIVES: To explore the association of maternal RA to pregnancy outcomes, especially preterm birth (PTB) and small for gestational age (SGA), in relation to disease activity and anti-rheumatic treatment before and during pregnancy. METHODS: By linking prospective clinical rheumatology registers (CRR) in Sweden (the Swedish Rheumatology Quality Register, SRQ) and Denmark (the Danish clinical quality register, DANBIO) with medical birth registers, we identified 1739 RA-pregnancies and 17 390 control-pregnancies (matched 1:10 on maternal age, birth year, parity) with delivery 2006-18. Disease activity (DAS28, CRP, HAQ score) and anti-rheumatic treatment 9 months before and during pregnancy were identified through CRR and prescribed drug registers. Using logistic regression, we estimated adjusted odds ratios (aOR) with 95% CI for PTB and SGA overall and stratified by disease activity and anti-rheumatic treatment before and during pregnancy, adjusting for maternal characteristics. RESULTS: We found increased aOR of PTB [1.92 (1.56-2.35)] and SGA [1.93 (1.45-2.57)] in RA-pregnancies vs control-pregnancies. For RA-pregnancies with DAS28-CRP ≥4.1 vs <3.2 during pregnancy, aOR was 3.38 (1.52-7.55) for PTB and 3.90 (1.46-10.4) for SGA. Use of oral CS (yes/no) during pregnancy resulted in an aOR of 2.11 (0.94-4.74) for PTB. The corresponding figure for biologics was 1.38 (0.66-2.89). Combination therapy, including biologics before pregnancy, was a marker of increased risk of both PTB and SGA. CONCLUSION: During pregnancy, disease activity rather than treatment seems to be the most important risk factor for PTB and SGA in RA. Women with RA should be carefully monitored during pregnancy, especially if they have moderate to high disease activity or/and are treated with extensive anti-rheumatic treatment.

Effectiveness and safety of infliximab dose escalation in patients with refractory Takayasu arteritis: A real-life experience from a monocentric cohort.

OBJECTIVES: To evaluate effectiveness and safety of infliximab dose escalation in Takayasu arteritis (TAK) patients. To identify factors associated with refractoriness to standard-dose infliximab. METHODS: Medical records of infliximab-treated TAK patients from a large single-centre observational cohort were reviewed. Infliximab therapy duration, concomitant therapies, and reasons for dose escalation and therapy suspension were evaluated. Occurrence of adverse events was recorded. A comparison between patients who maintained infliximab standard-dose and those who needed dose-escalation was performed. Factors associated with refractoriness to standard dose were analysed. RESULTS: Forty-one patients were included. Starting infliximab dose was 5 mg/kg 6-weekly and 28 patients (68%) needed dose escalation. Persistence/recurrence of clinical symptoms was the most frequent reason for escalation. Median therapy duration was 39 (IQR, 26-61) months in the standard-dose group and 68 (38-87) months in the intensified-dose group. In the intensified-dose-group, infliximab was suspended in eight patients (29%) after a median of 38 (31-71) months, due to loss of response (n = 7) or patient's request (n = 1). Patients in the intensified-dose group had a higher number of relapses (3.4 vs 0.8 events/patient) and received a higher cumulative steroid dose (1.7 [1.6-2.3] vs 1.3 [1-1.6] g/month of prednisone). Three patients from the intensified-dose group had serious infections; one patient from the standard-dose group developed paradoxical psoriasis. At univariate analysis, age at diagnosis and age at infliximab start were associated with infliximab escalation. CONCLUSION: In TAK, dose escalation is safe and allows to optimise infliximab durability in refractory patients. Younger patients seem to be more refractory to standard dosages.

Discontinuation of biologic DMARDs in a real-world population of patients with rheumatoid arthritis in remission: outcome and risk factors.

OBJECTIVES: Data from randomized controlled trials have shown the feasibility of discontinuation of bDMARD therapy in patients with RA that have reached remission. Criteria for selecting patients that are likely to remain in remission are still incompletely defined. We aimed to identify predictors of successful discontinuation of bDMARD therapy in the Swiss Clinical Quality Management (SCQM) registry, a real-world cohort of RA patients. METHODS: RA patients in DAS28-ESR remission who stopped bDMARD/tsDMARD treatment were included. Loss of remission was defined as a DAS28-ESR > 2.6 or restart of a bDMARD/tsDMARD. Time to loss of remission was the main outcome. Kaplan-Meier methods were applied and Cox regression was used for multivariable analyses adjusting for confounding factors. Missing data were imputed using multiple imputation. RESULTS: A total of 318 patients in a bDMARD/tsDMARD-free remission were followed between 1997 and 2017. In total, 241 patients (76%) lost remission after a median time of 0.9 years (95% CI: 0.7, 1.0). The time to loss of remission was shorter in women, in patients with a longer disease duration >4yrs and in patients who did not meet clinical disease activity index (CDAI) remission criteria at baseline. Remission was longer in patients with csDMARD therapy during b/tsDMARD free remission [hazard ratio (HR) 0.8, P =0.05, 95% CI: 0.6, 1.0]. CONCLUSION: In a real-world patient population, the majority of patients who discontinued b/tsDMARD treatment lost remission within <1 year. Our study confirms that fulfilment of more rigorous remission criteria and csDMARD treatment increases the chance of maintaining b/tsDMARD-free remission.

Recent progress in treatments of rheumatoid arthritis: an overview of developments in biologics and small molecules, and remaining unmet needs.

Through treatment with biological DMARDs (bDMARDs) or targeted synthetic (tsDMARDs) such as Janus kinase (JAK) inhibitors in addition to MTX, clinical remission has become a realistic therapeutic goal for the majority of patients with RA, and sustained remission facilitates prevention of joint damage and physical dysfunction. Long-term safety and sustained inhibition of structural changes and physical dysfunction by bDMARDs have been reported. The development of next-generation bDMARDs and expansion of their indications to various autoimmune diseases are expected. Five JAK inhibitors show comparable efficacy to bDMARDs, and the latest ones are effective for overcoming difficult-to-treat RA regardless of prior medications. Patients treated with JAK inhibitors should be adequately screened and monitored for infection, cardiovascular disorders, thrombosis, malignancies and so on. Advances in therapeutic strategies, including the differential use of therapeutic drugs and de-escalation of treatment after remission induction, are prioritized.

Lymphoma risks in patients with rheumatoid arthritis treated with biological drugs-a Swedish cohort study of risks by time, drug and lymphoma subtype.

OBJECTIVES: To estimate the association between biological DMARDs (bDMARDs; overall and by drug) as used in RA and the risk of malignant lymphomas including subtypes. METHODS: By linking nationwide Swedish registers we identified cohorts of patients with RA initiating treatment with a bDMARD (n = 16 392), bDMARD-naïve (n = 55 253), an age- and sex-matched general population comparator cohort (n = 229 047), and all incident lymphomas 2001-16. We used Cox regression to calculate hazard ratios (HRs) of lymphoma taking calendar period and other factors into account. RESULTS: There were 82 lymphomas among the bDMARD-treated patients with RA, crude incidence rate 76/100 000 person-years, and 310 lymphomas among the bDMARD-naïve patients with RA, crude incidence rate 90/100 000 person-years. This resulted in an adjusted HR (aHR) associated with bDMARD treatment (vs not) of 1.08 (95% CI: 0.83, 1.41). The corresponding aHR for bDMARD-treated and bDMARD-naïve vs the general population was 1.65 (95% CI: 1.31, 2.08) and 1.56 (95% CI: 1.37, 1.78) respectively. Restricting follow-up period to after 2006, the aHR of lymphoma for patients with RA starting a first bDMARD vs bDMARD-naïve was 0.69 (95% CI: 0.47, 1.00), and for bDMARD treated vs patients with RA switching from one conventional synthetic DMARDs to another, aHR was 0.46 (95% CI: 0.28, 0.73). There were no signals of different risks with any particular TNF inhibitor (TNFi) agent. We found no different lymphoma subtype pattern following bDMARD therapy. CONCLUSION: Treatment with bDMARDs, including both TNFi and non-TNFi bDMARDs, does not further increase the lymphoma risk in RA; instead, bDMARD treatment may actually reduce the excess lymphoma risk in RA.

Doppler ultrasound predicts successful discontinuation of biological DMARDs in rheumatoid arthritis patients in clinical remission.

OBJECTIVE: To assess the ability of ultrasound to predict successful tapering and successful discontinuation of biological DMARDs (bDMARDs) at the 2-year follow-up in RA patients in sustained remission. METHODS: Patients in sustained remission (DAS28-CRP ≤ 2.6) and with no radiographic progression the previous year tapered bDMARDs according to a standardized regime. A total of 119 of these patients were included in this ultrasound substudy. At baseline, clinical assessment, MRI, X-ray and ultrasound of 24 joints were performed. Ultrasound-detected synovitis was defined and scored 0-3 using the OMERACT scoring system at the joint level for both grey-scale and Doppler activity. Sum scores for each ultrasound modality were calculated for 24 joints at the patient level. The final state of treatment was assessed after 2 years. The predictive value of ultrasound measures for successful tapering and discontinuation at the 2-year follow-up was assessed via logistic regression analyses. RESULTS: Negative IgM-RF [odds ratio (OR) = 0.29, 95% CI: 0.10-0.85; P = 0.024] and lower Doppler sum score of 24 joints (OR = 0.44, 95% CI: 0.15, 0.87; P = 0.014) were independent predictors for successful discontinuation of bDMARDs at the 2-year follow-up. The predictive value of the Doppler sum score was independent of MRI findings. Previous numbers of bDMARDs were predictive of successful tapering (OR = 0.58, 95% CI: 0.35, 0.91; P = 0.018), whereas ultrasound was not. Clinical parameters were not predictive of successful tapering/discontinuation. CONCLUSION: Doppler sum score was an independent predictor for successful discontinuation of bDMARDs at the 2-year follow-up-the odds for achieving successful discontinuation decreased by 56% per one-unit increase in Doppler sum score. Ultrasound could not predict successful tapering.

Increased proportion of comorbidities but no deterioration of sexual quality of life during a 5-year follow-up in patients with axial spondyloarthritis in the biologic treatment era.

OBJECTIVE: To explore patient perception of sexual quality of life (SQOL), an important category of QOL, in male and female patients with axial SpA (axSpA) after a 5 year follow-up. METHODS: A broad spectrum of demographic, disease-related, treatment and SQOL data was collected at baseline and at the 5 year follow-up. SQOL was assessed by the SQOL-Female (SQOL-F) questionnaire. For statistical analysis, McNemar's tests, paired t-tests and multiple regression analyses were applied. RESULTS: A total of 245 axSpA patients (168 men and 77 women) from outpatient clinics were examined (mean age 46 years, mean disease duration 11.9 years at baseline). Compared with baseline, the patients had lower CRP, lower Maastricht Ankylosing Spondylitis Enthesitis Scores, lower BASFI scores, less use of smoking and significantly more patients were treated with biologic DMARDs at the 5 year follow-up. Patient perception of SQOL was basically unchanged at the 5 year follow-up despite a significantly increased proportion of comorbidities, including cardiovascular, endocrine and gastrointestinal disease. A decrease in SQOL after 5 years was observed only in patients exercising <1 h/week at baseline (P = 0.048) and in patients >65 years old. CONCLUSION: In our axSpA patients, no statistically significant changes in SQOL were observed over 5 years, despite a significant increase in comorbidities. Overall disease symptoms decreased, indicating better disease control. Increased use of biologic drugs at the 5 year follow-up may have contributed to this favourable outcome.

New pharmacotherapy options for noninfectious posterior uveitis.

INTRODUCTION: Noninfectious inflammation of the posterior eye segment represents an important cause of visual impairment. It often affects relatively young people and causes a significant personal and social impact. Although steroids and nonbiologic- Disease-Modifying Antirheumatic Drugs (nbDMARDs) are effective both in acute and long- lasting diseases, however they are increasingly being replaced by biologic (DMARDs). bDMARD. This article therefore aims to identify recent advances in the therapy of noninfectious posterior segment uveitis. METHODS: A Medline-search was conducted using the terms: nbDMARD, bDMARD, posterior uveitis, intermediate uveitis, treatment, corticosteroid. In addition, clinical studies were included as registered at ClinicalTrials.gov. RESULTS: Currently two major lines of treatments can be identified: (1) the intraocular application of anti-inflammatory agents and (2) the introduction of new agents, e.g., (bDMARDs) and small-molecule-inhibitors. Whereas intravitreal treatments have the advantage to avoid systemic side effects, new systemic agents are progressively earning credit on the basis of their therapeutic effects. CONCLUSION: Even when current treatment strategies are still hampered by the limited number of randomized controlled trials, promising progress and continuous efforts are seen.

Predictors of successful discontinuation of biologic and targeted synthetic DMARDs in patients with rheumatoid arthritis in remission or low disease activity: a systematic literature review.

OBJECTIVE: To systematically review possible predictors of successful discontinuation of biologic or targeted synthetic DMARDs (b/tsDMARDs) in RA patients in remission or low disease activity. METHODS: MEDLINE database and Cochrane Library were scanned for studies that discontinued b/tsDMARDs in remission/low disease activity and searched for predictors of successful discontinuation. Additionally, EULAR and ACR meeting abstracts were hand searched. RESULTS: Thirty-four studies with a total of 5724 patients were included. Predictors of successful b/tsDMARD discontinuation were (number of studies): low disease activity (n = 13), better physical function (n = 6), low or absence of rheumatoid factor (n = 5) or ACPA (n = 3), low levels of CRP (n = 3) or ESR (n = 3), shorter disease duration (n = 3), low signals of disease activity by ultrasound (n = 3). Only one study with high risk of bias was identified on tsDMARD discontinuation. CONCLUSION: Several predictors of successful bDMARD discontinuation were identified. Although studies are heterogeneous, these predictors may inform clinical decision making in patients who are considered for a potential bDMARD discontinuation.

Safety and efficacy of rituximab biosimilar (CT-P10) in systemic sclerosis: an Italian multicentre study.

OBJECTIVES: Recent data have shown a significant efficacy of rituximab (RTX) in SSc. An RTX biosimilar (RTX-B) is a more affordable option. We assessed the safety and efficacy of an RTX-B (CT-P10) in SSc. METHODS: SSc patients treated with RTX-B with at least 6 months of follow-up were retrospectively identified from six Italian referral centres. SSc patients naïve to RTX-B (RTX-Bn) or already treated with RTX originator and switched to an RTX-B (RTX-Bs) were evaluated. A comprehensive assessment of disease characteristics and organ involvement at baseline and after 6 months was obtained. RESULTS: Thirty-three SSc patients were selected: 29 (87.9%) females, mean age 51.6 years (s.d. 14.2), mean disease duration 9.8 years (s.d. 8.1); 21 (64.5%) with dcSSc, 20 (60.1%) anti-topoisomerase I, 7 (21.2%) anti-RNA polymerase III and 6 (18.2%) anti-centromere positive. Seventeen (51.5%) were RTX-Bn and 16 were on RTX-Bs (48.5%). RTX was introduced because of skin progression in 18 patients (54.5%), interstitial lung disease (ILD) worsening in 11 (33.3%) and arthritis in 12 (36.4%). All patients were previously treated with immunosuppressants. At RTX-B introduction, 21 (63.6%) patients were on concomitant immunosuppressants: 15 (71.4%) on MMF and 6 (28.6%) on MTX. Twenty-three (69.7%) were on low-dose steroids. After 6 months, a significant reduction of the modified Rodnan skin score (mRSS), 28-joint DAS and CRP was observed (P = 0.002, 0.005 and 0.008, respectively); the mRSS significantly improved both in RTX-Bn (P < 0.024) and RTX-Bs patients (P < 0.031). No significant changes were observed for lung function tests, either in the entire cohort or in the subgroup of ILD patients. Only one RTX-Bs patient experienced transient neutropenia. CONCLUSION: Our data suggest that RTX-B can represent a cheaper option in SSc patients, as it is effective in improving skin and joint involvement and in stabilizing lung function.

The association between the biological disease-modifying anti-rheumatic drugs and the incidence of diabetes: A systematic review and meta-analysis.

Whether the use of biological disease-modifying anti-rheumatic drugs (bDMARDs) would influence the risk of new-onset diabetes remains uncertain. Therefore, we performed a systematic review and meta-analysis to evaluate the association between the use of bDMARDs and the incidence of diabetes in patients with systemic inflammatory conditions. Pubmed, Medline, Embase and the Cochrane Central Register of Controlled Trials were searched for studies published from January 2000 to March 2020. Studies conducted in systemic inflammatory conditions with reports of the incidence of diabetes in subjects treated with bDMARDs were included. With 22 randomized controlled trials and 3 cohort studies included, the overall result indicated that compared with non-bDMARD treatment, the use of bDMARDs was significantly associated with decreased incidence of diabetes in patients with systemic inflammatory conditions (RR = 0.56, 95 % CI, 0.43 to 0.74, P < 0.001, I2 = 69 %), especially in patients with in rheumatoid arthritis (RR = 0.54, 95 % CI, 0.38 to 0.76, P = 0.0005, I2 = 26). Reduced risk of new-onset diabetes was observed in studies with follow-up more than 1 year (RR = 0.73, 95 % CI, 0.54 to 0.99, P = 0.04, I2 = 88). New-onset diabetes was less frequent in patients with TNF-α inhibitor treatment (RR = 0.54, 95 % CI, 0.48 to 0.60, P < 0.001, I2 = 42 %) and abatacept treatment (RR = 0.44, 95 % CI, 0.34 to 0.58, P < 0.001, I2 = 3 %), which might be associated with the inhibition of TNF-α mediated inflammatory responses and dysregulated T cell activation and immune responses respectively. Further investigations are required to validate the glucose metabolism protective effect of bDMARDs and clarify the underlying mechanisms of the crosstalk between bDMARDs and diabetes.

Anti-rheumatic treatment and prosthetic joint infection: an observational study in 494 elective hip and knee arthroplasties.

BACKGROUND: Surgical site infections are more frequent among patients with rheumatic disease. To what extent this is related to immunosuppressive antirheumatic drugs is unclear, as is the value of discontinuing medication perioperatively. The aim of study was to assess the rate of surgical site infections after knee and hip replacement in patients with inflammatory joint disease, with an emphasis on periprosthetic joint infection, and to investigate the influence of treatment with disease-modifying antirheumatic drugs (DMARDs) in this regard. METHODS: Data were collected from 494 primary elective hip (51.4%) and knee arthroplasties, along with demographic and medication data. The primary outcome was surgical site infection during the first year after surgery. RESULTS: In 78% (n = 385) of the cases the patient used 1 to 3 disease-modifying antirheumatic drugs perioperatively. Thirty-two percent (n = 157) of patients used a TNF-alpha inhibitor. The rate of surgical site infection was 3.8% (n = 19). The rate of periprosthetic joint infection was 1.4% (n = 7), all of which occurred after knee arthroplasty. Periprosthetic joint infection occurred in only 1 patient medicating perioperatively with a TNF-alpha inhibitor. CONCLUSION: Surgical site infections were not associated with ongoing medication with disease-modifying antirheumatic drugs. Due to the low event rate this should be interpreted with caution, but our center will maintain its routine of continuing treatment with TNF-alpha inhibitors perioperatively.