scholarly journals Comparative efficacy and safety of Janus kinase inhibitors and biological disease-modifying antirheumatic drugs in rheumatoid arthritis: a systematic review and network meta-analysis

2021 ◽  
Vol 13 ◽  
pp. 1759720X2199956
Author(s):  
Chenghua Weng ◽  
Leixi Xue ◽  
Qing Wang ◽  
Wentian Lu ◽  
Jiajun Xu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Meta Analysis ◽  
Certolizumab Pegol ◽  
Janus Kinase ◽  
Efficacy And Safety ◽  
Jak Inhibitors ◽  
Comparative Efficacy ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Disease Modifying

Objective: To evaluate the comparative efficacy and safety of Janus kinase (JAK) inhibitors and biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) and an inadequate response to at least one disease-modifying antirheumatic drug (DMARD). Methods: PubMed, Embase, Cochrane library and ClinicalTrials.gov were searched for relevant randomized controlled trials (RCTs) from inception to April 2020. The active drugs included three JAK inhibitors and eight bDMARDs while the control drugs included placebo or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Outcomes include American College of Rheumatology 20% response (ACR20), Disease Activity Score in 28 joints (DAS28), Health Assessment Questionnaire–Disability Index (HAQ-DI) and discontinuations for adverse events (AEs). We estimated summary odds ratios (ORs) and weighted mean differences (WMDs) using network meta-analysis with random effects. Results: Eighty-eight RCTs with 31,566 patients were included. All JAK inhibitors and bDMARDs were more effective than placebo in ACR20 (ORs ranging between 3.05 and 5.61), DAS28 (WMDs ranging between −1.91 and −0.80) and HAQ-DI (WMDs ranging between −0.34 and −0.21). Tocilizumab, certolizumab pegol and upadacitinib showed relatively good efficacy in these three outcomes according to their relative ranking. Notably, tocilizumab was more effective than other active drugs in DAS28 (WMDs ranging between −1.11 and −0.49). Compared with the lower recommended doses, increasing the doses of JAK inhibitors (baricitinib 4 mg versus 2 mg, tofacitinib 10 mg versus 5 mg and upadacitinib 30 mg versus 15 mg) cannot provide significant additional benefits. In terms of discontinuations for AEs, all active drugs showed no significant difference compared with placebo except certolizumab pegol [OR 1.65, 95% credible interval (CrI) 1.06–2.61] and rituximab (3.17, 1.11–10.80). Conclusions: Tocilizumab, certolizumab pegol and upadacitinib may have relatively good efficacy in patients with RA after treatment failure with csDMARDs. RA patients taking a JAK inhibitor may have a preference for a lower recommended dose.

scholarly journals Biologic disease modifying antirheumatic drugs and Janus kinase inhibitors in paediatric rheumatology – what we know and what we do not know from randomized controlled trials

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Tatjana Welzel ◽  
Carolyn Winskill ◽  
Nancy Zhang ◽  
Andreas Woerner ◽  
Marc Pfister
Keyword(s):  
Certolizumab Pegol ◽  
Paediatric Rheumatology ◽  
Janus Kinase ◽  
Pharmacokinetic Data ◽  
Disease Course ◽  
Jak Inhibitors ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Age Dependent ◽  
Disease Modifying

Abstract Background Biologic disease modifying antirheumatic drugs (bDMARDs) and Janus Kinase (JAK) inhibitors are prescribed in adult and paediatric rheumatology. Due to age-dependent changes, disease course, and pharmacokinetic processes paediatric patients with inflammatory rheumatic diseases (PiRD) differ from adult rheumatology patients. Methods A systematic literature search for randomized clinical trials (RCTs) in PiRD treated with bDMARDs/JAK inhibitors was conducted on Medline, clinicaltrials.gov, clinicaltrialsregister.eu and conference abstracts as of July 2020. RCTs were included if (i) patients were aged ≤20 years, (ii) patients had a predefined rheumatic diagnosis and (iii) RCT reported predefined outcomes. Selected studies were excluded in case of (i) observational or single arm study or (ii) sample size ≤5 patients. Study characteristics were extracted. Results Out of 608 screened references, 65 references were selected, reporting 35 unique RCTs. All 35 RCTs reported efficacy while 34/3 provided safety outcomes and 16/35 provided pharmacokinetic data. The most common investigated treatments were TNF inhibitors (60%), IL-1 inhibitors (17%) and IL-6 inhibitors (9%). No RCTs with published results were identified for baricitinib, brodalumab, certolizumab pegol, guselkumab, risankizumab, rituximab, sarilumab, secukinumab, tildrakizumab, or upadacitinib. In patients with juvenile idiopathic arthritis (JIA) 25/35 RCTs were conducted. The remaining 10 RCTs were performed in non-JIA patients including plaque psoriasis, Kawasaki Disease, systemic lupus erythematosus and non-infectious uveitis. In JIA-RCTs, the control arm was mainly placebo and the concomitant treatments were either methotrexate, non-steroidal anti-inflammatory drugs (NSAID) or corticosteroids. Non-JIA patients mostly received NSAID. There are ongoing trials investigating abatacept, adalimumab, baricitinib, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, risankizumab, secukinumab, tofacitinib and tildrakizumab. Conclusion Despite the FDA Modernization Act and support of major paediatric rheumatology networks, such as the Pediatric Rheumatology Collaborative Study Group (PRCSG) and the Paediatric Rheumatology International Trials Organization (PRINTO), which resulted in drug approval for PiRD indications, there are limited RCTs in PiRD patients. As therapy response is influenced by age-dependent changes, pharmacokinetic processes and disease course it is important to consider developmental changes in bDMARDs/JAK inhibitor use in PiRD patients. As such it is critical to collaborate and conduct international RCTs to appropriately investigate and characterize efficacy, safety and pharmacokinetics of bDMARDs/JAK inhibitors in paediatric rheumatology.

scholarly journals EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update

2020 ◽  
pp. annrheumdis-2019-216655 ◽  
Author(s):  
Josef S Smolen ◽  
Robert B M Landewé ◽  
Johannes W J Bijlsma ◽  
Gerd R Burmester ◽  
Maxime Dougados ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Task Force ◽  
Certolizumab Pegol ◽  
Janus Kinase ◽  
Sustained Remission ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Levels Of Evidence ◽  
Eular Recommendations ◽  
Disease Modifying

ObjectivesTo provide an update of the European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) management recommendations to account for the most recent developments in the field.MethodsAn international task force considered new evidence supporting or contradicting previous recommendations and novel therapies and strategic insights based on two systematic literature searches on efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) since the last update (2016) until 2019. A predefined voting process was applied, current levels of evidence and strengths of recommendation were assigned and participants ultimately voted independently on their level of agreement with each of the items.ResultsThe task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering on sustained clinical remission is provided. Cost and sequencing of b/tsDMARDs are addressed. Initially, MTX plus GCs and upon insufficient response to this therapy within 3 to 6 months, stratification according to risk factors is recommended. With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD or JAK inhibitor should be added to the csDMARD. If this fails, any other bDMARD (from another or the same class) or tsDMARD is recommended. On sustained remission, DMARDs may be tapered, but not be stopped. Levels of evidence and levels of agreement were mostly high.ConclusionsThese updated EULAR recommendations provide consensus on the management of RA with respect to benefit, safety, preferences and cost.

Mixed Treatment Comparison of the Treatment Discontinuations of Biologic Disease-Modifying Antirheumatic Drugs in Adults with Rheumatoid Arthritis

2012 ◽  
Vol 46 (11) ◽  
pp. 1491-1505 ◽  
Author(s):  
Rishi J Desai ◽  
Richard A Hansen ◽  
Jaya K Rao ◽  
Tania M Wilkins ◽  
Elizabeth A Harden ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Meta Analysis ◽  
Mixed Treatment Comparison ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Biologic Dmards ◽  
Treatment Comparison ◽  
Mixed Treatment ◽  
Disease Modifying

BACKGROUND: Introduction of biologic disease-modifying antirheumatic drugs (DMARDs) has considerably changed treatment options for rheumatoid arthritis (RA) over the past decade. Very little information is available on comparative discontinuation rates of the biologics. OBJECTIVE: To compare treatment discontinuations for 9 biologic DMARDs in adults with RA. METHODS: We searched electronic databases through May 2012 to retrieve randomized controlled trials (RCTs) of patients with RA that compared biologic DMARDs with placebo or another biologic DMARD. The primary outcome was treatment discontinuation during the blinded phase of the trials, measured as overall withdrawals, withdrawals resulting from lack of efficacy, and withdrawals resulting from adverse events. Random-effects meta-analysis estimated the effect size for individual agents, and adjusted indirect comparisons were made between biologics using mixed treatment comparisons (MTC) meta-analysis. RESULTS: Forty-four trials were included in the analysis. In comparison with placebo, biologics were less likely to be withdrawn because of lack of efficacy (OR 0.22, 95% CI 0.17 to 0.27) and more likely to be withdrawn because of an adverse event (OR 1.41, 95% CI 1.16 to 1.70). Based on the MTC, certolizumab had the most favorable overall withdrawal profile, followed by etanercept and rituximab. Certolizumab had lower relative withdrawal rates resulting from lack of efficacy than adalimumab, anakinra, and infliximab. Anakinra had higher relative withdrawal rates resulting from lack of efficacy than most other biologics. Certolizumab and infliximab had more, while etanercept had fewer, withdrawals because of adverse events than most other drugs. CONCLUSIONS: Based on MTC using data from RCTs, differences in discontinuation rates were observed, generally favoring certolizumab, etanercept, and rituximab over other biologic DMARDs. These potential differences need to be further explored in head-to-head trials or well-conducted observational studies.

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