Safety of biologic immunosuppressants in pregnant women with immune-mediated inflammatory diseases.

BACKGROUND: Immune-mediated inflammatory diseases (IMIDs) typically affect women of childbearing age. One of the challenges in treating these women during pregnancy is to manage the disease while minimizing or avoiding the use of disease-modifying antirheumatic drugs (DMARDs) that may increase the risk to the mother or fetus. Biologic therapy has transformed the management of these patients. This study aimed to evaluate the maternal-fetal safety and perinatal outcomes in pregnant women with IMID exposed to biologic DMARDs either preconceptionally or during pregnancy and compare them with women using conventional DMARDs and a group of healthy pregnant women. METHODS: We conducted a retrospective study with prospective follow-up of pregnant women with IMID at a single center. We analyzed baseline maternal demographic characteristics, diseases, DMARDs, and maternal-fetal outcomes. RESULTS: A cohort of 244 pregnancies was studied. One hundred twenty-eight patients met classificatory criteria for rheumatic and musculoskeletal diseases (RMD) or inflammatory bowel disease (IBD), and 116 pregnancies of healthy women were evaluated from the same study period. One hundred and one pregnancies in IMID patients (89.84 %) occurred under immunosuppressive treatment, 78.91 % of IMID pregnancies were under cDMARD (33.59 % exclusive cDMARD), 56.25 % under bDMARD, and 27.34 % under oral glucocorticoids. Anti-TNF was the most frequent (88.88 %) bDMARD and was used in 50.78 % of the IMIDs. There was at least one flare in 37.10 % of the IMID pregnancies, and 9.38 % experienced more than one. Among flares, 43.48 % happened in the first trimester, 34.78 % in the second trimester, and 19.57 % in the third. Flares were more frequent in the RMD patients compared with IBD (p = 0.041; OR 2.15, 95%CI: 1.03-4.52). Flare was associated with discontinuation of bDMARD before the eighth week of gestation (p = 0.016), but especially in the second (p = 0.042) and third trimester (p = 0.012). Maternal infections were an infrequent complication overall (7.66 %), although more frequent in patients with IMIDs (p = 0.004) but were not associated with cDMARD or bDMARD. IMID patients needed assisted reproductive techniques (ART) more often (p = 0.001, OR 2.83, 95%CI: 1.02-7.90). More cesarean sections were performed in gestations under treatment with bDMARD (p = 0.020) and especially in those under treatment with anti-TNF. Aneuploidies calculation risk and fetal malformations were not correlated with DMARDs (cDMARDs, bDMARDs, or its combination) nor with any of the DMARDs individually preconcepcionally or during gestation. Small for gestational age (SGA) newborns were higher in patients with IMIDs however, it was not associated with DMARD use. DISCUSSION: In general, patients with IMIDs who require treatment with bDMARDs have a more severe or refractory disease prior to gestation. In our cohort, we found a higher risk of flare among patients with bDMARDs, especially when those were suspended early. Among maternal outcomes, we found that IMID patients needed ART more often. This is probably, first of all, because of maternal age. Among fetal outcomes, there are no differences in congenital malformations in the IMIDs and healthy patients and were not correlated with DMARDs. CONCLUSION: The use of bDMARDs was effective in disease control and safe from a maternal-fetal point of view, with no increase in prematurity, SGA, malformations, or infections.

New-onset atrial fibrillation in seropositive rheumatoid arthritis: association with disease-modifying anti-rheumatic drugs treatment.

OBJECTIVE: Atrial fibrillation (AF) is a potentially lethal complication that leads to increased hospitalization, disability and mortality. Furthermore, the risk of cardiovascular disease is increased in RA. We evaluated whether DMARD treatment is associated with incident AF in patients with seropositive RA (SPRA). METHODS: The South Korean Health Insurance Review and Assessment Service database was used to identify patients newly diagnosed with SPRA between 2010 and 2020. A nested case-control analysis was performed to match AF-affected patients to unaffected controls for age, sex, follow-up duration, and index year of SPRA diagnosis at a 1:4 ratio. Adjusted conditional logistic regression was used to identify the predictive factors for AF. RESULTS: Of the 108 085 patients with SPRA, 2,629 (2.4%) developed new-onset AF, and the proportion of females was ∼67%. In the matched population, pre-existing comorbidities of hypertension, chronic kidney disease, and heart failure were associated with increased risk of AF. Meanwhile, the use of methotrexate (MTX) decreased the risk of incident AF [adjusted odds ratio (aOR), 0.89], whereas the use of leflunomide (LEF) increased AF (aOR, 1.21). In a subgroup of patients aged ≥50 years, LEF and adalimumab increased the occurrence of AF, while MTX decreased AF in males and LEF increased this risk in females. CONCLUSION: Although the number of subjects developing new-onset AF was small, MTX decreased and LEF increased incident AF in patients with RA. Especially, a distinct pattern of AF risk with DMARDs usage was observed according to age and sex.

The information required by people with inflammatory arthritis to take methotrexate: a mixed-methods systematic review.

OBJECTIVES: This mixed-methods systematic review aimed to identify and synthesize knowledge of the characteristics, content, and preferred format of information to support people with inflammatory arthritis (IA) to take methotrexate. METHODS: A literature search using MEDLINE, The Cochrane Library, Embase, CINAHL, PsychInfo, GreyEU, Web of Science and Open Dissertation was conducted to identify all studies published from 2000 to December 2022. Included studies detailed factors related to methotrexate (MTX) related information needs of people with inflammatory arthritis ≥ 18 years in English. Joanna Briggs Institute Guidelines (JBI) for convergent integrated mixed-methods systematic reviews were followed using validated tools for data extraction and quality. Data was analysed using reflexive thematic analysis. RESULTS: Thirteen studies (seven quantitative, two mixed-methods and four qualitative) were included involving 3425 adults, mainly female n = 2434 (71%), age 20-84 years. An overarching theme of a requirement for person-centred care was developed with three interlinking themes: 1: Accepting the need for treatment with MTX, 2: Concerns about taking MTX, 3: A need for tailored information and support. Limitations of the evidence were use of heterogeneous outcome measures and instruments to measure information needs. CONCLUSION: People with IA have individual, multi-faceted information, and support needs about MTX that are often unresolved when a one-size-fits-all approach is used. The findings can inform rheumatology training to support a person-centred approach to identifying and addressing specific needs, concerns and the development of consistent easy-to-understand accessible MTX information.

Treatment patterns of individualized real-life tapering approaches based on shared decision-making in rheumatoid arthritis.

OBJECTIVE: To provide real-world evidence on patient-individual tapering patterns of disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients in daily clinical practice. METHODS: Data obtained through a controlled prospective cohort study in Germany conducted from July 2018 to March 2021 were analyzed. Participants consist of RA patients in sustained remission who were eligible for DMARD tapering at enrolment. Data from RA patients who experienced tapering of DMARDs at least once during the observational period (n = 200) were used. Descriptive analyses of medical outcomes at baseline and at time of first tapering, time to first tapering, tapering patterns by substance group, and tapering intensity were documented. RESULTS: We did not observe meaningful differences in either disease activity or quality of life measures between substance groups at enrolment, time of first tapering, and at 6 or 12 months after tapering. Median time until first tapering varied between substance groups (csDMARDs: 108 days; bDMARDs: 189 days; combination: 119 days). Most patients received one iteration of tapering only (147/200 patients, 73.5%). Dose reduction was applied for patients treated with csDMARDs (79/86 patients, 91.8%), spacing of interval was the most frequent strategy for patients treated with bDMARDs only (43/48 patients, 89.5%). Necessity for increased DMARD dosage was observed in only 10% of patients (20/200). Tapering intensity by substance was overall heterogenous, indicating high individualization. CONCLUSION: We identify highly heterogeneous tapering patterns between substance groups and within substances. Identification and recognition of patient-individual approaches of tapering will help to further improve the management of RA for both patients and rheumatologists.

Pharmacological treatment patterns in patients with juvenile idiopathic arthritis in the Netherlands: a real-world data analysis.

OBJECTIVE: To investigate medication prescription patterns among children with JIA, including duration, sequence and reasons for medication discontinuation. METHODS: This study is a single-centre, retrospective analysis of prospective data from the electronic medical records of JIA patients receiving systemic therapy aged 0-18 years between 1 April 2011 and 31 March 2019. Patient characteristics (age, gender, JIA subtype) and medication prescriptions were extracted and analysed using descriptive statistics, Sankey diagrams and Kaplan-Meier survival methods. RESULTS: Over a median of 4.2 years follow-up, the 20 different medicines analysed were prescribed as monotherapy (n = 15) or combination therapy (n = 48 unique combinations) among 236 patients. In non-systemic JIA, synthetic DMARDs were prescribed to almost all patients (99.5%), and always included MTX. In contrast, 43.9% of non-systemic JIA patients received a biologic DMARD (mostly adalimumab or etanercept), ranging from 30.9% for oligoarticular persistent ANA-positive JIA, to 90.9% for polyarticular RF-positive JIA. Among systemic JIA, 91.7% received a biologic DMARD (always including anakinra). When analysing medication prescriptions according to their class, 32.6% involved combination therapy. In 56.8% of patients, subsequent treatment lines were initiated after unsuccessful first-line treatment, resulting in 68 unique sequences. Remission was the most common reason for DMARD discontinuation (44.7%), followed by adverse events (28.9%) and ineffectiveness (22.1%). CONCLUSION: This paper reveals the complexity of pharmacological treatment in JIA, as indicated by: the variety of mono- and combination therapies prescribed, substantial variation in medication prescriptions between subtypes, most patients receiving two or more treatment lines, and the large number of unique treatment sequences.

A real-world 2-year prospective study of medication tapering in patients with well-controlled rheumatoid arthritis within the rheumatoid arthritis medication tapering (RHEUMTAP) cohort.

OBJECTIVES: This study had two aims: (i) to investigate outcomes of medication tapering in stable RA patients on biologic or targeted synthetic disease-modifying anti-rheumatic drugs (bDMARDs/tsDMARDs) and conventional synthetic DMARDs (csDMARDs) in a real-world prospective cohort; and (ii) to evaluate possible predictors of flare with medication taper. METHODS: A prospective cohort of patients with RA in sustained remission or low disease activity while on stable bDMARD/tsDMARDs +/- csDMARDs for at least 6 months underwent medication tapering/stopping and was tracked for 2 years. Patients were evaluated for flares in four groups: no taper, only bDMARD/tsDMARD taper, only csDMARD taper and both csDMARD and bDMARD/tsDMARD taper. RESULTS: The RHEUMTAP cohort included 131 patients that met eligibility criteria, of which 52 patients underwent a medication taper. Flare was experienced by 15 patients in the taper and two in the no-taper groups. Patients undergoing any taper/stop overall were 10 times more likely to experience a flare compared with those not tapered (HR 10.43, 95% CI 2.98-36.53, P = 0.0002). The group tapering bDMARD/tsDMARD had 31 times higher risk of flare (HR 31.43, 95% CI 6.35-155.55, P <0.0001) than the no-taper group. Patients tapering both csDMARDs and bDMARD/tsDMARDs had 18 times higher risk of flare than the no-taper group (HR 18.45, 95% CI 2.55-133.37, P = 0.0039). The only csDMARD taper group had a 91% lower risk of flare than the bDMARD/tsDMARD taper group (HR 0.09, 95% CI 0.01-0.69, P = 0.0213). CONCLUSION: In our real-world prospective RHEUMTAP cohort study on the outcomes of different medication tapering groups in well-controlled RA, patients who tapered or stopped bDMARDs/tsDMARDs with or without background therapy were more likely to experience a flare than patients that did not taper any medications and those that tapered only csDMARDs.

Patient perspectives on tapering biologic or targeted synthetic therapy in well-controlled rheumatoid arthritis and comparison with providers' perspectives.

OBJECTIVE: We examined patient and providers' perspectives on tapering biologic or targeted synthetic disease modifying antirheumatic drugs (bDMARD or tsDMARD) in well-controlled RA to determine which factors influence their long-term treatment decisions. METHODS: A standardized phone survey was administered to patients with well-controlled RA based on electronic health record review. Providers were also surveyed. Univariate and multivariable regression analysis was performed with odds ratios (OR) and 95% CI. RESULTS: Sixty-two patients and 11 providers completed the survey. In total, 39 (63%) patients would consider a bDMARD/tsDMARD taper. Patients were more likely to consider a taper if they thought their RA was well-controlled (OR 8.02, 95% CI 2.15-29.99, P = 0.002) and of shorter duration (OR 0.94, 95% CI 0.89-0.99, P = 0.02). Patients were less likely to consider a taper if older (OR 0.95, 95% CI 0.91-1.0, P = 0.05), if they were being treated with conventional synthetic DMARDs (OR 0.25, 95% CI 0.07-0.86, P = 0.0275) or daily glucocorticoids (OR 0.08, 95% CI 0.02-0.44, P = 0.0033). Patients' and providers' top concerns about long-term bDMARD/tsDMARD use were malignancy and infection. Their concerns about tapering were worsening pain, flare and loss of function. Patients were more likely to consider a bDMARD/tsDMARD taper than providers (63% vs 36%). CONCLUSION: Patients who have had well-controlled RA are more likely to consider tapering bDMARD/tsDMARD when not being treated with csDMARDs or glucocorticoids. Patients and providers shared similar concerns regarding long-term use and tapering of bDMARD/tsDMARD, but patients were more likely to consider a taper.

The added value of predictive biomarkers in treat-to-target strategies for rheumatoid arthritis patients: a conceptual modelling study.

OBJECTIVES: To quantify the additional value of a hypothetical biomarker predicting response to treatment for RA regarding efficacy and costs by using a modelling design. METHODS: A Markov model was built comparing a usual care T2T strategy with a biomarker-steered strategy for RA patients starting biologic therapy. Outcome measures include time spent in remission or low disease activity (LDA) and costs. Four additional scenario analyses were performed by varying biomarker or clinical care characteristics: (i) costs of the biomarker; (ii) sensitivity and specificity of the biomarker; (iii) proportion of eligible patients tapering; and (iv) medication costs. RESULTS: In the base model, patients spent 2.9 months extra in LDA or remission in the biomarker strategy compared with usual care T2T over 48 months. Total costs were €43 301 and €42 568 for, respectively, the usual care and biomarker strategy, and treatment costs accounted for 91% of total costs in both scenarios. Cost savings were driven due to patients in the biomarker strategy experiencing remission or LDA earlier, and starting tapering sooner. Cost-effectiveness was not so much driven by costs or test characteristics of the biomarker (scenario 1/2), but rather by the level of early and proactive tapering and drug costs (scenarios 3/4). CONCLUSIONS: The use of a biomarker for prediction of response to b/tsDMARD treatment in RA can be of added value to current treat-to-target clinical care. However, gains in efficacy are modest and cost gains are depending on a combination of early proactive tapering and high medication costs.

Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from the KEEPsAKE 1 study.

OBJECTIVE: PsA is a chronic disease with heterogeneous clinical manifestations requiring treatment options with long-term efficacy and safety. In this follow-up analysis, the 52-week efficacy and safety of risankizumab 150 mg in patients with active PsA who had previous inadequate response/intolerance to one or more conventional synthetic DMARDs (csDMARD-IR) were evaluated. METHODS: KEEPsAKE 1 is an ongoing, global, phase 3 study with a 24-week, double-blind, placebo-controlled period (period 1) and an open-label extension period (period 2). In period 1, eligible patients were randomized 1:1 to receive subcutaneous risankizumab 150 mg or placebo at weeks 0, 4 and 16. At week 24 (period 2), all continuing patients received open-label risankizumab 150 mg every 12 weeks through week 208. RESULTS: At week 24, 57.3% of risankizumab-treated patients (n = 483) achieved ≥20% improvement in ACR criteria (ACR20) vs 33.5% of placebo-treated patients (n = 481; P < 0.001). At week 52, 70.0% of patients who were randomized to receive continuous risankizumab therapy and 63.0% of patients who were randomized to receive placebo in period 1 and then receive risankizumab at week 24 achieved ACR20. Similar result trends were observed for other efficacy measures. Risankizumab was well tolerated through 52 weeks of treatment with a consistent safety profile from week 24 through week 52. CONCLUSION: In patients with active PsA who were csDMARD-IR, continuous risankizumab treatment demonstrated robust long-term efficacy and was well tolerated through 52 weeks of treatment. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, KEEPsAKE1, NCT03675308.

Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from the KEEPsAKE 2 study.

OBJECTIVE: PsA is a chronic inflammatory disease in which the skin and joints are affected. In this follow-up analysis, the 52-week efficacy and safety of risankizumab 150 mg in patients with active PsA who had previous inadequate response/intolerance to one or two biologic therapies (Bio-IR) or one or more conventional synthetic DMARDs (csDMARD-IR) were evaluated. METHODS: In the ongoing, phase 3, KEEPsAKE 2 trial, patients with active PsA were randomized 1:1 to receive subcutaneous risankizumab 150 mg or placebo at weeks 0, 4 and 16 (period 1). At week 24 (period 2), patients who received placebo were switched to risankizumab, and all patients received risankizumab 150 mg every 12 weeks from weeks 28 to 208. RESULTS: At week 24, 51.3% of risankizumab-treated patients (n = 224) achieved ≥20% improvement in ACR criteria (ACR 20) vs 26.5% of placebo-treated patients (n = 220; P < 0.001). At week 52, 58.5% of patients randomized to receive continuous risankizumab achieved ACR20, and 55.7% of patients who switched from placebo to risankizumab at week 24 achieved ACR20. Similar trends were observed for other efficacy measures. Rates of serious treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation remained stable through week 52, and no deaths were reported. CONCLUSION: Risankizumab was well tolerated and improved symptoms of PsA in Bio-IR/csDMARD-IR patients, with a consistent long-term safety profile from weeks 24 to 52. TRIAL REGISTRATION: United States National Library of Medicine clinical trials database www.clinicaltrials.gov; KEEPsAKE 2; NCT03671148.

The effect of anti-inflammatory treatment on depressive symptoms in spondyloarthritis: does the type of drug matter?

OBJECTIVE: To investigate the effect of pharmacological treatment of SpA on depressive symptoms and explore whether this effect differs between drug classes. METHODS: Data from the observational Assessment of SpondyloArthritis international Society Health Index Validation Study were used. Patients were assessed at baseline and after initiation of NSAIDs/conventional synthetic DMARDs (csDMARDs)/TNF inhibitors (TNFis). Depressive symptoms were assessed with the Hospital Anxiety and Depression Scale depression subscale [HADS-D; 0-21 (best-worst)]. Covariables included demographics and disease characteristics, including disease activity [Ankylosing Spondylitis Disease Activity Score (ASDAS)/BASDAI]. The change in HADS-D from baseline was compared between treatments (NSAIDs/csDMARDs/TNFis) with analysis of variance and multivariable regression analysis. RESULTS: A total of 304 patients were included; 102/45/157 initiated NSAIDs/csDMARDs/TNFis and 260 (85%) / 44 (15%) had axial/peripheral SpA. At baseline, the mean HADS-D was 6.9 (s.d. 4.2); 126 (42%) were possibly depressed (HADS-D ≥8) and 66 (22%) were probably depressed (HADS-D ≥11). At follow-up, depressive symptoms significantly improved in all treatment groups. In multivariable regression without disease activity measures, initiating TNFis compared with NSAIDs was associated with greater improvement in depressive symptoms [ß = -1.27 (95% CI -2.23, -0.32)] and lower odds of possible depression at follow-up [odds ratio 0.47 (95% CI 0.23, 0.94)]. This association was attenuated after additional adjustment for disease activity (ASDAS/BASDAI) but not CRP. csDMARDs did not differ from NSAIDs regarding their effect on HADS-D. Between-drug class results were confirmed in axial SpA (axSpA), although less clear in peripheral SpA. CONCLUSION: Treatment of active SpA also improves depressive symptoms. Especially in axSpA, TNFis have a greater effect than NSAIDs, which is mainly explained by a stronger effect on disease activity. We found no evidence for a direct link between CRP-mediated inflammation and depressive symptoms in SpA.

Quantifying hospital-associated costs, and accompanying travel costs and productivity losses, before and after withdrawing tumour necrosis factor-alfa inhibitors in juvenile idiopathic arthritis.

OBJECTIVE: To quantify differences in hospital-associated costs, and accompanying travel costs and productivity losses, before and after withdrawing TNFi in JIA patients. METHODS: Retrospective analysis of prospectively collected data from electronic medical records of paediatric JIA patients treated with TNFi, which were either immediately discontinued, spaced (increased treatment interval) or tapered (reduced subsequent doses). Costs of hospital-associated resource use (consultations, medication, radiology procedures, laboratory testing, procedures under general anaesthesia, hospitalisation) and associated travel costs and productivity losses were quantified during clinically inactive disease until TNFi withdrawal (pre-withdrawal period) and compared with costs during the first and second year after withdrawal initiation (first and second year post-withdrawal). RESULTS: Fifty-six patients were included of whom 26 immediately discontinued TNFi, 30 spaced and zero tapered. Mean annual costs were €9,165/patient on active treatment (pre-withdrawal) and decreased significantly to €5,063/patient (-44.8%) and €6,569/patient (-28.3%) in the first and second year post-withdrawal, respectively (p< 0.05). Of these total annual costs, travel costs plus productivity losses were €834/patient, €1,180/patient, and €1,320/patient, in the three periods respectively. Medication comprised 80.7%, 61.5% and 72.4% of total annual costs in the pre-withdrawal, first, and second year post-withdrawal period, respectively. CONCLUSION: In the first two years after initiating withdrawal, the total annual costs are decreased compared with the pre-withdrawal period. However, cost reductions were lower in the second year compared with the first year post-withdrawal, primarily due to restarting or intensifying biologics. To support biologic withdraw decisions, future research should assess the full long-term societal cost impacts, and include all biologics.

JAK inhibitors in difficult-to-treat adult-onset Still's disease and systemic-onset juvenile idiopathic arthritis.

OBJECTIVES: Excessive and inappropriate production of pro-inflammatory cytokines plays a key role in Still's disease. Janus kinase inhibitor (JAKi) agents mainly block pro-inflammatory cytokine pathways, notably IL-6 and IFN. The objective was to assess the efficacy and safety of JAKi agents in difficult-to-treat systemic JIA or adult-onset Still's disease (AOSD). METHODS: This retrospective study was based on a national survey conducted in the departments of rheumatology, paediatric rheumatology and internal medicine of French hospitals regarding systemic JIA and AOSD patients who received JAKi agents. The data were collected with a standardized questionnaire and analysed at different times (treatment initiation, months 1, 3 and 6 and the end of follow-up). RESULTS: Nine patients (seven adults) were included. All patients showed inadequate response to CS or conventional synthetic or biologic DMARDs. Baricitinib was used in five patients, ruxolitinib in two, tofacitinib in two and upadacitinib in one. A JAKi was used combined with CS in all but two patients. A JAKi was associated with anakinra and CS in one patient, and with MTX, anakinra and CS in another. The median (range) follow-up was 16 (1-33) months. Two cases out of nine showed complete remission, 3/9 partial response and 4/9 treatment failure. At the last visit, CS could be decreased but not stopped. Tolerance of the JAKi was acceptable (no severe adverse events). CONCLUSION: JAKi agents may be a therapeutic option for some patients with difficult-to-treat Still's disease, especially those with partial response to medium- or high-dose CS or biologics.

COVID-19 admissions and mortality in patients with early inflammatory arthritis: results from a UK national cohort.

OBJECTIVE: To describe the risks and predictors of coronavirus disease 2019 (COVID-19) hospitalization and mortality among patients with early inflammatory arthritis (EIA), recruited to the National Early Inflammatory Arthritis Audit (NEIAA). METHODS: NEIAA is an observational cohort. We included adults with EIA from Feb 2020 to May 2021. Outcomes of interest were hospitalization and death due to COVID-19, using NHS Digital linkage. Cox proportional hazards were used to calculate hazard ratios for outcomes according to initial treatment strategy, with adjustment for confounders. RESULTS: From 14 127 patients with EIA, there were 143 hospitalizations and 47 deaths due to COVID-19, with incidence rates per 100 person-years of 0.93 (95% CI 0.79, 1.10) for hospitalization and 0.30 (95% CI 0.23, 0.40) for death. Increasing age, male gender, comorbidities and ex-smoking were associated with increased risk of worse COVID-19 outcomes. Higher baseline DAS28 was not associated with COVID-19 admissions [confounder adjusted hazard ratio (aHR) 1.10; 95% CI 0.97, 1.24] or mortality (aHR 1.11; 95% CI 0.90, 1.37). Seropositivity was not associated with either outcome. Higher symptom burden on patient-reported measures predicted worse COVID-19 outcomes. In unadjusted models, CS associated with COVID-19 death (HR 2.29; 95% CI 1.02, 5.13), and SSZ monotherapy associated with COVID-19 admission (HR 1.92; 95% CI 1.04, 3.56). In adjusted models, associations for CS and SSZ were not statistically significant. CONCLUSION: Patient characteristics have stronger associations with COVID-19 than the initial treatment strategy in patients with EIA. An important limitation is that we have not looked at treatment changes over time.

How to Use Janus Kinase Inhibitors in the Treatment of Rheumatoid Arthritis? A Clinical Assessment of Risks and Benefits.

PURPOSE OF REVIEW: To provide an updated understanding of risks and benefits of Janus kinase inhibitors (JAKi) versus biologic disease-modifying antirheumatic drugs (bDMARDs) in the management of rheumatoid arthritis (RA). RECENT FINDINGS: Shared decision-making is needed in choosing between JAKi and bDMARDs. Cardiovascular disease, malignancy, and thromboembolic events guide this choice. In patients with active RA despite methotrexate use, tumor necrosis factor inhibitor is conditionally favored over JAKi for low-cardiovascular-risk patients and strongly favored in those with pre-existing cardiovascular disease or multiple cardiovascular risk factors. Suboptimal treatment of treatment-refractory RA patients may pose a greater absolute cardiovascular risk than with JAKi use. Use of aspirin and statin may be considered to reduce cardiovascular risk. New safety data on JAKi has redefined the treatment approach in RA. JAKi remains an important oral medication option in active RA despite treatment with bDMARDs, especially in those with low cardiovascular risk.

Efficacy and safety of curcumin in maintaining remission during disease-modifying antirheumatic drug withdrawal in rheumatoid arthritis at 52 weeks: a phase III double-blind, randomized placebo-controlled trial.

Curcumin has anti-inflammatory properties but current evidence is limited to advocate its use in rheumatoid arthritis (RA). We explored whether curcumin could maintain remission in patients with RA while tapering conventional synthetic Disease-Modifying Antirheumatic Drugs (csDMARD). In this patient-and investigator-blinded trial, adults with RA in sustained remission for more than six months were randomized to oral curcumin (1 g) with piperine (5 mg) twice daily or matching placebo. Patients who had received biological DMARDs or curcumin supplements in the last 6 months were excluded. csDMARD were tapered and stopped sequentially as per a fixed protocol. The primary outcome was flare-free survival at 52 weeks. The secondary outcomes were flare rate, correlation of serum curcuminoid levels with flares and safety. 200 patients (100 per arm) entered the trial with comparable baseline characteristics. Per protocol analysis included 92 and 93 participants in the curcumin and the placebo group, respectively. Flare-free survival at week 52 was similar between both groups (60% versus 64%; p = 0.76). The median time to flare was similar [Curcumin: 219 days (IQR: 123) versus placebo: 214 days (95.8); p = 0.067]. Cox proportionate regression modelling showed that the flare-free survival was independent of serum curcuminoid levels [adjusted HR = 0.99 (95% CI: 0.97-1.0)]. The model showed that flare-free survival was not associated with age, gender, seropositivity, or csDMARD used at baseline. No serious adverse effects were noted. Curcumin did not impact the flare-free survival in patients with RA in remission during the tapering of csDMARDs despite achieving adequate serum levels.Trial registration: CTRI/2018/04/013279.

[Psoriatic arthritis : Clinical challenges and pharmaceutical management]. / Psoriasisarthritis : Klinische Herausforderungen und medikamentöses Management.

Psoriatic arthritis (PsA) is a systemic immune-mediated inflammatory disease of the musculoskeletal system, which is accompanied by a chronic and progressive course. It is characterized by different clinical manifestations and can severely impair the quality of life and function of patients due to the existing heterogeneity of the manifestations. The (early) diagnosis of PsA and individualized therapeutic management in routine clinical practice are difficult due to the enormous clinical variability. In addition to the appearance of arthritis of the peripheral joints, there can be involvement of the axial skeleton, skin psoriasis, nail psoriasis, enthesitis and dactylitis. The clinical appearance, course of the disease, risk factors and pathophysiological mechanisms of PsA have been extensively researched in recent decades. With the associated better understanding of the disease, new treatment options and goals for effective treatment have also been established.

The effect of smoking on response to methotrexate in rheumatoid arthritis patients: A systematic review and meta-analysis.

OBJECTIVES: In the current study, we aimed to investigate the effect of smoking on inadequate response to methotrexate (MTX-IR) in rheumatoid arthritis (RA) patients. METHODS: We searched PubMed, Embase, and Web of Science until 6 June 2022. Observational or interventional studies investigating MTX-IR in RA patients based on smoking status were included. Two independent reviewers assessed the risk of bias and the certainty of the evidence using the Risk of Bias in Nonrandomized Studies-of Interventions and Grades of Recommendation, Assessment, Development, and Evaluation tools, respectively. RESULTS: We included 23 studies in the systematic review and 13 in the meta-analysis. Of the 13 included studies, 6 had a moderate risk, 3 had a serious risk, and 4 had a critical risk of bias. The overall random-effect meta-analysis suggested that smokers were 58% more likely to be MTX-IR when compared with nonsmokers [odds ratio (OR) 1.58, 95% confidence interval 1.21-2.06; P = .001; I2 = 69.3%]. The common-effect meta-analysis of the adjusted ORs demonstrated an overall OR of 2.69 (1.88-3.83; P < .001; I2 = 27.1%). CONCLUSIONS: The current study showed that smoking is a significant predictor of MTX-IR, especially in disease-modifying antirheumatic drug-naïve early RA patients, as most of the included studies in the meta-analysis consisted of this population.

Selection of treatment regimens based on shared decision-making in patients with rheumatoid arthritis on remission in the FREE-J study.

OBJECTIVE: To compare the outcome of various treatment de-escalation regimens in patients with RA who achieved sustained remission. METHODS: At period 1, 436 RA patients who were treated with MTX and bDMARDs and had maintained DAS28(ESR) at <2.6 were divided into five groups based on shared patient/physician decision-making; continuation, dose reduction and discontinuation of MTX or bDMARDs. At end of year 1, patients who achieved DAS28(ESR) <3.2 were allowed to enrol in period 2 for treatment using the de-escalation regimens for another year. The primary and secondary endpoints were the proportion of patients with DAS28(ESR) <2.6 at year 1 and 2, respectively. RESULTS: Based on shared decision-making, 81.4% elected de-escalation of treatment and 48.4% selected de-escalation of MTX. At end of period 1, similar proportions of patients maintained DAS28(ESR) <2.6 (continuation, 85.2%; MTX dose reduction, 79.0%; MTX-discontinuation, 80.0%; bDMARD dose reduction, 73.9%), although the rate was significantly different between the continuation and bDMARD-discontinuation. At end of period 2, similar proportions of patients of the MTX groups maintained DAS28(ESR) <2.6 (continuation or de-escalation), but the rates were significantly lower in the bDMARD-discontinuation group. However, half of the latter group satisfactorily discontinued bDMARDs. Adverse events were numerically lower in MTX and bDMARD-de-escalation groups during period 1 and 2, compared with the continuation group. CONCLUSIONS: After achieving sustained remission by combination treatment of MTX/bDMARDs, disease control was achieved comparably by continuation, dose reduction or discontinuation of MTX and dose reduction of bDMARDs at end of year 1. Subsequent de-escalation of MTX had no impacts on disease control but decreased adverse events in year 2.

Patient and rheumatologist perspectives on tapering DMARDs in rheumatoid arthritis: a qualitative study.

OBJECTIVES: To understand the perspectives of patients and rheumatologists for tapering DMARDs in RA. METHODS: Using semi-structured interview guides, we conducted individual interviews and focus groups with RA patients and rheumatologists, which were audiotaped and transcribed. We conducted a pragmatic thematic analysis to identify major themes, comparing and contrasting different views on DMARD tapering between patients and rheumatologists. RESULTS: We recruited 28 adult patients with RA (64% women; disease duration 1-54 y) and 23 rheumatologists (52% women). Attitudes across both groups towards tapering DMARDs were ambivalent, ranging from wary to enthusiastic. Both groups expressed concerns, particularly the inability to 'recapture' the same level of disease control, while also acknowledging potential positive outcomes such as reduced drug harms. Patient tapering perspectives (whether to and when) changed over time and commonly included non-biologic DMARDs. Patient preferences were influenced by lived experiences, side effects, previous tapering experiences, disease trajectory, remission duration and current life roles. Rheumatologists' perspectives varied on timing and patient profile to initiate tapering, and were informed by both data and clinical experience. Patients expressed interest in shared decision-making (SDM) and close monitoring during tapering, with ready access to their health-care team if problems arose. Rheumatologists were generally open to tapering (not stopping), though sometimes only when requested by their patients. CONCLUSION: The perspectives of patients and rheumatologists on tapering DMARDs in RA vary and evolve over time. Rheumatologists should periodically discuss DMARD tapering with patients as part of SDM, and ensure monitoring and flare management plans are in place.