scholarly journals Safety of synthetic and biological DMARDs: a systematic literature review informing the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis

2020 ◽  
pp. annrheumdis-2019-216653 ◽  
Author(s):  
Alexandre Sepriano ◽  
Andreas Kerschbaumer ◽  
Josef S Smolen ◽  
Désirée van der Heijde ◽  
Maxime Dougados ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Literature Review ◽  
Systematic Literature Review ◽  
Observational Studies ◽  
Janus Kinase ◽  
Jak Inhibitors ◽  
Eular Recommendations ◽  
Increased Risk ◽  
Safety Outcomes ◽  
Risk Of Cancer

ObjectivesTo perform a systematic literature review (SLR) concerning the safety of synthetic (s) and biological (b) disease-modifying anti rheumatic dugs (DMARDs) to inform the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis (RA).MethodsAn SLR of observational studies comparing safety outcomes of any DMARD with another intervention for the management of RA. A comparator group was required for inclusion. For treatments still without registry data (eg, sarilumab and the Janus kinase (JAK) inhibitors baricitinib, upadacitinib), randomised controlled trials (RCTs) and long-term extensions (LTEs) were used. Risk of bias (RoB) was assessed according to standard procedures.ResultsForty-two observational studies fulfilled the inclusion criteria, addressing safety outcomes with bDMARDs and sDMARDs. Nine studies showed no difference in the risk of serious infections across bDMARDs and two studies (high RoB) showed an increased risk with bDMARDs compared with conventional synthetic (cs) DMARDs (adjusted incidence rate ratio 3.1–3.9). The risk of Herpes zoster infection was similar across bDMARDs, but one study showed an increased risk with tofacitinib compared with abatacept (adjusted HR (aHR) 2.0). Five studies showed no increased risk of cancer for bDMARDs compared with csDMARDs. An increased risk of lower intestinal perforation was found for tocilizumab compared with csDMARDs (aHR 4.5) and tumour necrosis factor inhibitor (TNFi) (aHR 2.6–4.0). Sixty manuscripts reported safety data from RCTs/LTEs. Overall, no unexpected safety outcomes were found, except for the possibly increased risk of venous thromboembolism (VTE) with JAK inhibitors.ConclusionData obtained by this SLR confirm the known safety profile of bDMARDs. The risk of VTE in RA, especially in patients on JAK inhibitors, needs further evaluation.

scholarly journals Safety of synthetic and biological DMARDs: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis

2014 ◽  
Vol 73 (3) ◽  
pp. 529-535 ◽  
Author(s):  
Sofia Ramiro ◽  
Cécile Gaujoux-Viala ◽  
Jackie L Nam ◽  
Josef S Smolen ◽  
Maya Buch ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Literature Review ◽  
Systematic Literature Review ◽  
Observational Studies ◽  
Certolizumab Pegol ◽  
Eligibility Criteria ◽  
Biological Dmards ◽  
Eular Recommendations ◽  
Increased Risk ◽  
Safety Outcomes

ObjectivesTo update the evidence for the safety of synthetic disease-modifying antirheumatic drugs (sDMARDs), glucocorticoids (GC) and biological DMARDs (bDMARDs) in patients with rheumatoid arthritis (RA) to inform the European League Against Rheumatism (EULAR) recommendations for the management of RA.MethodsSystematic literature review (SLR) of observational studies (including registries). Interventions were any bDMARD (anakinra, infliximab, etanercept, adalimumab, rituximab, abatacept, tocilizumab, golimumab or certolizumab pegol) or sDMARD (methotrexate, leflunomide, hydroxychloroquine, sulfasalazine, gold/auranofin, azathioprine, chlorambucil, chloroquine, cyclosporin, cyclophosphamide, mycophenolate, minocycline, penicillamine, tacrolimus or tofacitinib) and a comparator was required. Information on GCs was collected from the included studies. All safety outcomes were included.ResultsForty-nine observational studies addressing diverse safety outcomes of therapy with bDMARDs met eligibility criteria. Substantial heterogeneity precluded meta-analysis of any of the outcomes. Patients on tumour necrosis factor inhibitors (TNFi) compared to patients on conventional sDMARDs had a higher risk of serious infections (adjusted HR (aHR) 1.1–1.8), a higher risk of tuberculosis, and an increased risk of infection by herpes zoster cannot be excluded. Patients on TNFi did not have an increased risk for malignancies in general, lymphoma or non-melanoma skin cancer, but the risk of melanoma may be slightly increased (aHR 1.5). From the studies identified on conventional sDMARDs, no new safety signals were found.ConclusionsThe findings from this SLR confirm the known safety pattern of sDMARDs and bDMARDs for the treatment of RA.

Sicherheit von synthetischen und biologischen DMARDs für die Behandlung der rheumatoiden Arthritis

2020 ◽  
Vol 2 (4) ◽  
pp. 161-162
Author(s):  
Carmen-Marina Mihai
Keyword(s):  
Observational Studies ◽  
Safety Data ◽  
Janus Kinase ◽  
Jak Inhibitors ◽  
Eular Recommendations ◽  
Increased Risk ◽  
Safety Outcomes ◽  
Factor Inhibitor ◽  
Adjusted Incidence Rate ◽  
Risk Of Cancer

<b>Objectives:</b> To perform a systematic literature review (SLR) concerning the safety of synthetic (s) and biological (b) disease-modifying anti rheumatic dugs (DMARDs) to inform the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis (RA). <b>Methods:</b> An SLR of observational studies comparing safety outcomes of any DMARD with another intervention for the management of RA. A comparator group was required for inclusion. For treatments still without registry data (eg, sarilumab and the Janus kinase (JAK) inhibitors baricitinib, upadacitinib), randomized controlled trials (RCTs) and long-term extensions (LTEs) were used. Risk of bias (RoB) was assessed according to standard procedures. <b>Results:</b> Forty-two observational studies fulfilled the inclusion criteria, addressing safety outcomes with bDMARDs and sDMARDs. Nine studies showed no difference in the risk of serious infections across bDMARDs and two studies (high RoB) showed an increased risk with bDMARDs compared with conventional synthetic (cs) DMARDs (adjusted incidence rate ratio 3.1–3.9). The risk of Herpes zoster infection was similar across bDMARDs, but one study showed an increased risk with tofacitinib compared with abatacept (adjusted HR (aHR) 2.0). Five studies showed no increased risk of cancer for bDMARDs compared with csDMARDs. An increased risk of lower intestinal perforation was found for tocilizumab compared with csDMARDs (aHR 4.5) and tumour necrosis factor inhibitor (TNFi) (aHR 2.6–4.0). Sixty manuscripts reported safety data from RCTs/LTEs. Overall, no unexpected safety outcomes were found, except for the possibly increased risk of venous thromboembolism (VTE) with JAK inhibitors. <b>Conclusion:</b> Data obtained by this SLR confirm the known safety profile of bDMARDs. The risk of VTE in RA, especially in patients on JAK inhibitors, needs further evaluation.

scholarly journals Safety of synthetic and biological DMARDs: a systematic literature review informing the 2016 update of the EULAR recommendations for management of rheumatoid arthritis

2017 ◽  
Vol 76 (6) ◽  
pp. 1101-1136 ◽  
Author(s):  
Sofia Ramiro ◽  
Alexandre Sepriano ◽  
Katerina Chatzidionysiou ◽  
Jackie L Nam ◽  
Josef S Smolen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Literature Review ◽  
Systematic Literature Review ◽  
Observational Studies ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Eligibility Criteria ◽  
Increased Risk ◽  
Serious Infections ◽  
Safety Outcomes

ObjectivesTo assess the safety of synthetic (s) and biological (b) disease-modifying antirheumatic drugs (DMARDs) for the management of rheumatoid arthritis (RA) to inform the European League Against Rheumatism recommendations for the management of RA.MethodsSystematic literature review (SLR) of observational studies comparing any DMARD with another intervention for the management of patients with RA. All safety outcomes were included. A comparator group was required for the study to be included. Risk of bias was assessed with the Hayden's tool.ResultsTwenty-six observational studies addressing diverse safety outcomes of therapy with bDMARDs met eligibility criteria (15 on serious infections, 4 on malignancies). Substantial heterogeneity precluded meta-analysis. Together with the evidence from the 2013 SLR, based on 15 studies, 7 at low risk of bias, patients on bDMARDs compared with patients on conventional sDMARDs had a higher risk of serious infections (adjusted HR (aHR) 1.1 to 1.8)—without differences across bDMARDs—a higher risk of tuberculosis (aHR 2.7 to 12.5), but no increased risk of infection by herpes zoster. Patients on bDMARDs did not have an increased risk of malignancies in general, lymphoma or non-melanoma skin cancer, but the risk of melanoma may be slightly increased (aHR 1.5).ConclusionsThese findings confirm the known safety pattern of bDMARDs, including both tumour necrosis factor-α inhibitor (TNFi) and non-TNFi, for the treatment of RA.

scholarly journals SAT0052 THERAPEUTIC STRATEGIES IN DIFFICULT-TO-TREAT RHEUMATOID ARTHRITIS: PRELIMINARY RESULTS OF A SYSTEMATIC LITERATURE REVIEW INFORMING THE 2020 EULAR RECOMMENDATIONS FOR THE MANAGEMENT OF DIFFICULT-TO-TREAT RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 957-957
Author(s):  
N. M. T. Roodenrijs ◽  
A. Hamar ◽  
M. Kedves ◽  
G. Nagy ◽  
J. M. Van Laar ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Literature Review ◽  
Systematic Literature Review ◽  
Therapeutic Strategies ◽  
Eular Recommendations ◽  
Management Interventions ◽  
Fatigue Exercise ◽  
Factor Inhibitor ◽  
Management Recommendations ◽  
Sat 1

Background:Rheumatoid arthritis (RA) patients treated according to European League Against Rheumatism (EULAR) recommendations failing ≥2 biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) with a different mode of action who still have complaints which may be suggestive of active disease may be defined as suffering from ‘difficult-to-treat RA’. Management recommendations for RA focus predominantly on the earlier phases of the disease and specific recommendations for difficult-to-treat RA patients are currently lacking.1Objectives:To systematically summarise evidence in the literature on pharmacological and non-pharmacological therapeutic strategies for difficult-to-treat RA patients, informing the 2020 EULAR recommendations for the management of difficult-to-treat RA.Methods:A systematic literature review (SLR) was performed: PubMed, Embase and Cochrane databases were searched up to December 2019. Relevant papers were selected and appraised.Results:Thirty articles were selected for therapeutic strategies in patients with limited DMARD options due to contraindications, 73 for patients in whom previous b/tsDMARDs were not effective (‘true refractory RA’), and 51 for patients with predominantly non-inflammatory complaints. For patients with limited DMARD options, limited evidence was found on effective DMARD options for patients with concomitant obesity, and on safe DMARD options for patients with concomitant hepatitis B and C. In patients who failed ≥2 bDMARDs, tocilizumab, tofacitinib, baricitinib, upadacitinib and filgotinib were found to be more effective than placebo, but evidence was insufficient to prioritise. In patients who failed ≥1 bDMARD, there was a tendency of non-tumour necrosis factor inhibitor (TNFi) bDMARDs to be more effective than TNFi (Figure 1). Generally, b/tsDMARDs become less effective when patients failed more bDMARDs, this tendency was not clear for upadacitinib and filgotinib (Figure 2). In patients with predominantly non-inflammatory complaints (mainly function, pain and fatigue), exercise, education, psychological and self-management interventions were found to be of additional benefit.Conclusion:This SLR underscores the scarcity of evidence on the optimal treatment of difficult-to-treat RA patients. As difficult-to-treat RA is a newly defined disease state, all evidence is to an extent indirect. Several b/tsDMARDs were found to be effective in patients who failed ≥2 bDMARDs and generally effectiveness decreased with a higher number of failed bDMARDs. Additionally, a beneficial effect of non-pharmacological interventions was found on non-inflammatory complaints.References:[1] Smolen JSet al. Ann Rheum Dis2020. Epub ahead of print.Disclosure of Interests:Nadia M. T. Roodenrijs: None declared, Attila Hamar: None declared, Melinda Kedves: None declared, György Nagy: None declared, Jacob M. van Laar Grant/research support from: MSD, Genentech, Consultant of: MSD, Roche, Pfizer, Eli Lilly, BMS, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV, Paco Welsing: None declared

scholarly journals Paracetamol: not as safe as we thought? A systematic literature review of observational studies

2015 ◽  
Vol 75 (3) ◽  
pp. 552-559 ◽  
Author(s):  
Emmert Roberts ◽  
Vanessa Delgado Nunes ◽  
Sara Buckner ◽  
Susan Latchem ◽  
Margaret Constanti ◽  
...  
Keyword(s):  
Literature Review ◽  
Systematic Literature Review ◽  
Dose Response ◽  
Observational Studies ◽  
Relative Rate ◽  
Adult Population ◽  
Assessment Development ◽  
Increased Risk ◽  
General Adult Population ◽  
Paracetamol Toxicity

ObjectivesWe conducted a systematic literature review to assess the adverse event (AE) profile of paracetamol.MethodsWe searched Medline and Embase from database inception to 1 May 2013. We screened for observational studies in English, which reported mortality, cardiovascular, gastrointestinal (GI) or renal AEs in the general adult population at standard analgesic doses of paracetamol. Study quality was assessed using Grading of Recommendations Assessment, Development and Evaluation. Pooled or adjusted summary statistics were presented for each outcome.ResultsOf 1888 studies retrieved, 8 met inclusion criteria, and all were cohort studies. Comparing paracetamol use versus no use, of two studies reporting mortality one showed a dose–response and reported an increased relative rate of mortality from 0.95 (0.92 to 0.98) to 1.63 (1.58 to 1.68). Of four studies reporting cardiovascular AEs, all showed a dose–response with one reporting an increased risk ratio of all cardiovascular AEs from 1.19 (0.81 to 1.75) to 1.68 (1.10 to 2.57). One study reporting GI AEs reported a dose–response with increased relative rate of GI AEs or bleeds from 1.11 (1.04 to 1.18) to 1.49 (1.34 to 1.66). Of four studies reporting renal AEs, three reported a dose–response with one reporting an increasing OR of ≥30% decrease in estimated glomerular filtration rate from 1.40 (0.79 to 2.48) to 2.19 (1.4 to 3.43).DiscussionGiven the observational nature of the data, channelling bias may have had an important impact. However, the dose–response seen for most endpoints suggests a considerable degree of paracetamol toxicity especially at the upper end of standard analgesic doses.

Current evidence for a strategic approach to the management of rheumatoid arthritis with disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis

2010 ◽  
Vol 69 (6) ◽  
pp. 987-994 ◽  
Author(s):  
R Knevel ◽  
M Schoels ◽  
T W J Huizinga ◽  
D Aletaha ◽  
G R Burmester ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Literature Review ◽  
Clinical Outcome ◽  
Physical Function ◽  
Systematic Literature Review ◽  
Structural Damage ◽  
Task Force ◽  
Treatment Strategies ◽  
Current Evidence ◽  
Eular Recommendations

ObjectivesTo perform a systematic literature review of effective strategies for the treatment of rheumatoid arthritis (RA).MethodsAs part of a European League Against Rheumatism (EULAR) Task Force investigation, a literature search was carried out from January 1962 until February 2009 in PubMed/Ovid Embase/Cochrane and EULAR/American College of Rheumatism (ACR)) abstracts (2007/2008) for studies with a treatment strategy adjusted to target a predefined outcome. Articles were systematically reviewed and clinical outcome, physical function and structural damage were compared between intensive and less intensive strategies. The results were evaluated by an expert panel to consolidate evidence on treatment strategies in RA.ResultsThe search identified two different kinds of treatment strategies: strategies in which the reason for treatment adjustment differed between the study arms (‘steering strategies’, n=13) and strategies in which all trial arms used the same clinical outcome to adjust treatment with different pharmacological treatments (‘medication strategies’, n=7). Both intensive steering strategies and intensive medication strategies resulted in better outcome than less intensive strategies in patients with early active RA.ConclusionIntensive steering strategies and intensive medication strategies produce a better clinical outcome, improved physical function and less structural damage than conventional steering or treatment. Proof in favour of any steering method is lacking and the best medication sequence is still not known.

scholarly journals Efficacy of glucocorticoids, conventional and targeted synthetic disease-modifying antirheumatic drugs: a systematic literature review informing the 2016 update of the EULAR recommendations for the management of rheumatoid arthritis

2017 ◽  
Vol 76 (6) ◽  
pp. 1102-1107 ◽  
Author(s):  
Katerina Chatzidionysiou ◽  
Sharzad Emamikia ◽  
Jackie Nam ◽  
Sofia Ramiro ◽  
Josef Smolen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Literature Review ◽  
Systematic Literature Review ◽  
Treat To Target ◽  
Tight Control ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Eular Recommendations ◽  
Synthetic Dmards ◽  
Disease Modifying

ObjectivesTo perform a systematic literature review (SLR) informing the 2016 update of the recommendations for the management of rheumatoid arthritis (RA).MethodsAn SLR for the period between 2013 and 2016 was undertaken to assess the efficacy of glucocorticoids (GCs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and targeted synthetic DMARDs (tsDMARDs) (tofacitinib and baricitinib) in randomised clinical trials.ResultsFor GCs, four studies were included in the SLR. Patients without poor prognostic factors experienced benefit when GCs were added to methotrexate (MTX). Lower doses of GCs were similar to higher doses. For csDMARDs, two new studies comparing MTX monotherapy with combination csDMARD were included in the SLR. In the tREACH trial at the end of 12 months no difference between the groups in disease activity, functional ability and radiographic progression was seen, using principles of tight control (treat-to-target). In the CareRA trial, combination therapy with csDMARDs was not superior to MTX monotherapy and monotherapy was better tolerated.For tsDMARDs, tofacitinib and baricitinib were shown to be more effective than placebo (MTX) in different patient populations.ConclusionsAddition of GCs to csDMARD therapy may be beneficial but the benefits should be balanced against the risk of toxicity. Under tight control conditions MTX monotherapy is not less effective than combination csDMARDs, but better tolerated. Tofacitinib and baricitinib are efficacious in patients with RA, including those with refractory disease.

scholarly journals Risk and prognosis of SARS-CoV-2 infection and vaccination against SARS-CoV-2 in rheumatic and musculoskeletal diseases: a systematic literature review to inform EULAR recommendations

2021 ◽  
pp. annrheumdis-2021-221575
Author(s):  
Féline P B Kroon ◽  
Aurélie Najm ◽  
Alessia Alunno ◽  
Jan W Schoones ◽  
Robert B M Landewé ◽  
...  
Keyword(s):  
Risk Factor ◽  
Literature Review ◽  
Quality Assessment ◽  
Systematic Literature Review ◽  
Kinase Inhibitors ◽  
Musculoskeletal Diseases ◽  
Data Extraction ◽  
Case Definition ◽  
Janus Kinase ◽  
Increased Risk

ObjectivesPerform a systematic literature review (SLR) on risk and prognosis of SARS-CoV-2 infection and vaccination against SARS-CoV-2 in patients with rheumatic and musculoskeletal diseases (RMDs).MethodsLiterature was searched up to 31 May 2021, including (randomised) controlled trials and observational studies with patients with RMD. Pending quality assessment, data extraction was performed and risk of bias (RoB) was assessed. Quality assessment required provision of (1) an appropriate COVID-19 case definition, and (2a) a base incidence (for incidence data) or (2b) a comparator, >10 cases with the outcome and risk estimates minimally adjusted for age, sex and comorbidities (for risk factor data).ResultsOf 5165 records, 208 were included, of which 90 passed quality assessment and data were extracted for incidence (n=42), risk factor (n=42) or vaccination (n=14). Most studies had unclear/high RoB. Generally, patients with RMDs do not face more risk of contracting SARS-CoV-2 (n=26 studies) or worse prognosis of COVID-19 (n=14) than individuals without RMDs. No consistent differences in risk of developing (severe) COVID-19 were found between different RMDs (n=19). Disease activity is associated with worse COVID-19 prognosis (n=2), possibly explaining the increased risk seen for glucocorticoid use (n=13). Rituximab is associated with worse COVID-19 prognosis (n=7) and possibly Janus kinase inhibitors (n=3). Vaccination is generally immunogenic, though antibody responses are lower than in controls. Vaccine immunogenicity is negatively associated with older age, rituximab and mycophenolate.ConclusionThis SLR informed the July 2021 update of the European Alliance of Associations for Rheumatology recommendations for the management of RMDs in the context of SARS-CoV-2.

scholarly journals Risk of venous thromboembolism associated with Janus kinase inhibitors for rheumatoid arthritis: case presentation and literature review

2021 ◽  
Author(s):  
Shunsuke Mori ◽  
Fumihiko Ogata ◽  
Ryusuke Tsunoda
Keyword(s):  
Rheumatoid Arthritis ◽  
Diabetes Mellitus ◽  
Risk Factors ◽  
Pulmonary Embolism ◽  
Venous Thromboembolism ◽  
Disease Activity ◽  
Janus Kinase ◽  
Advanced Age ◽  
Jak Inhibitors ◽  
Increased Risk

AbstractJanus kinase (JAK) inhibitors have been developed as disease-modifying antirheumatic drugs. Despite the positive therapeutic impacts of JAK inhibitors, concerns have been raised regarding the risk of venous thromboembolism (VTE), such as deep vein thrombosis (DVT) and pulmonary embolism (PE). A recent post hoc safety analysis of placebo-controlled trials of JAK inhibitors in rheumatoid arthritis (RA) reported an imbalance in the incidence of VTE for a 4-mg daily dose of baricitinib versus placebo. In a recent postmarketing surveillance trial for RA, a significantly higher incidence of PE was reported in treatment with tofacitinib (10 mg twice daily) compared with tofacitinib 5 mg or tumor necrosis factor inhibitors. We also experienced a case of massive PE occurring 3 months after starting baricitinib (4 mg once daily) for multiple biologic-resistant RA. Nevertheless, the evidence to support the role of JAK inhibitors in VTE risk remains insufficient. There are a number of predisposing conditions and risk factors for VTE. In addition to the known risk factors that can provoke VTE, advanced age, obesity, diabetes mellitus, hypertension, hyperlipidemia, and smoking can also contribute to its development. Greater VTE risk is noted in patients with chronic inflammatory conditions, particularly RA patients with uncontrolled disease activity and any comorbidity. Prior to the initiation of JAK inhibitors, clinicians should consider both the number and strength of VTE risk factors for each patient. In addition, clinicians should advise patients to seek prompt medical help if they develop clinical signs and symptoms that suggest VTE/PE. Key Points• Patients with rheumatoid arthritis (RA) are at increased risk of venous thromboembolism (VTE), especially those with uncontrolled, high disease activity and those with comorbidities.• In addition to the well-known risk factors that provoke VTE events, advanced age and cardiovascular risk factors, such as obesity, diabetes mellitus, hypertension, hyperlipidemia, and smoking, should be considered risk factors for VTE.• Although a signal of VTE/pulmonary embolism (PE) risk with JAK inhibitors has been noted in RA patients who are already at high risk, the evidence is currently insufficient to support the increased risk of VTE during RA treatment with JAK inhibitors.• If there are no suitable alternatives, clinicians should prescribe JAK inhibitors with caution, considering both the strength of individual risk factors and the cumulative weight of all risk factors for each patient.

scholarly journals Pharmacological and non-pharmacological therapeutic strategies in difficult-to-treat rheumatoid arthritis: a systematic literature review informing the EULAR recommendations for the management of difficult-to-treat rheumatoid arthritis

RMD Open ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. e001512
Author(s):  
Nadia M T Roodenrijs ◽  
Attila Hamar ◽  
Melinda Kedves ◽  
György Nagy ◽  
Jacob M van Laar ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Literature Review ◽  
Goal Setting ◽  
Systematic Literature Review ◽  
Functional Disability ◽  
Therapeutic Strategies ◽  
Self Management ◽  
Eular Recommendations ◽  
Management Interventions ◽  
Pregnancy And Lactation

ObjectivesTo summarise, by a systematic literature review (SLR), the evidence regarding pharmacological and non-pharmacological therapeutic strategies in difficult-to-treat rheumatoid arthritis (D2T RA), informing the EULAR recommendations for the management of D2T RA.MethodsPubMed, Embase and Cochrane databases were searched up to December 2019. Relevant papers were selected and appraised.ResultsTwo hundred seven (207) papers studied therapeutic strategies. Limited evidence was found on effective and safe disease-modifying antirheumatic drugs (DMARDs) in patients with comorbidities and other contraindications that limit DMARD options (patients with obesity, hepatitis B and C, risk of venous thromboembolisms, pregnancy and lactation). In patients who previously failed biological (b-)DMARDs, all currently used b/targeted synthetic (ts-)DMARDs were found to be more effective than placebo. In patients who previously failed a tumour necrosis factor inhibitor (TNFi), there was a tendency of non-TNFi bDMARDs to be more effective than TNFis. Generally, effectiveness decreased in patients who previously failed a higher number of bDMARDs. Additionally, exercise, psychological, educational and self-management interventions were found to improve non-inflammatory complaints (mainly functional disability, pain, fatigue), education to improve goal setting, and self-management programmes, educational and psychological interventions to improve self-management.The identified evidence had several limitations: (1) no studies were found in patients with D2T RA specifically, (2) heterogeneous outcome criteria were used and (3) most studies had a moderate or high risk of bias.ConclusionsThis SLR underscores the scarcity of high-quality evidence on the pharmacological and non-pharmacological treatment of patients with D2T RA. Effectiveness of b/tsDMARDs decreased in RA patients who had failed a higher number of bDMARDs and a subsequent b/tsDMARD of a previously not targeted mechanism of action was somewhat more effective. Additionally, a beneficial effect of non-pharmacological interventions was found for improvement of non-inflammatory complaints, goal setting and self-management.

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