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 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 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.

scholarly journals EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2019 update

2020 ◽  
Vol 79 (6) ◽  
pp. 700-712 ◽  
Author(s):  
Laure Gossec ◽  
Xenofon Baraliakos ◽  
Andreas Kerschbaumer ◽  
Maarten de Wit ◽  
Iain McInnes ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Joint Damage ◽  
Janus Kinase ◽  
Collaborative Management ◽  
Sustained Remission ◽  
Tnf Inhibitor ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Eular Recommendations ◽  
Disease Modifying

ObjectiveTo update the European League Against Rheumatism (EULAR) recommendations for the pharmacological treatment of psoriatic arthritis (PsA).MethodsAccording to the EULAR standardised operating procedures, a systematic literature review was followed by a consensus meeting to develop this update involving 28 international taskforce members in May 2019. Levels of evidence and strengths of recommendations were determined.ResultsThe updated recommendations comprise 6 overarching principles and 12 recommendations. The overarching principles address the nature of PsA and diversity of both musculoskeletal and non-musculoskeletal manifestations; the need for collaborative management and shared decision-making is highlighted. The recommendations provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs and local glucocorticoid injections are proposed as initial therapy; for patients with arthritis and poor prognostic factors, such as polyarthritis or monoarthritis/oligoarthritis accompanied by factors such as dactylitis or joint damage, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drugs (bDMARDs) targeting tumour necrosis factor (TNF), interleukin (IL)-17A or IL-12/23 should be initiated, taking into account skin involvement if relevant. If axial disease predominates, a TNF inhibitor or IL-17A inhibitor should be started as first-line disease-modifying antirheumatic drug. Use of Janus kinase inhibitors is addressed primarily after bDMARD failure. Phosphodiesterase-4 inhibition is proposed for patients in whom these other drugs are inappropriate, generally in the context of mild disease. Drug switches and tapering in sustained remission are addressed.ConclusionThese recommendations provide stakeholders with an updated consensus on the pharmacological management of PsA, based on a combination of evidence and expert opinion.

scholarly journals Immediate Effect of Baricitinib on Arthritis and Biological Disease-Modifying Antirheumatic Drug-Induced Psoriasis-Like Skin Lesions in Two Patients with Rheumatoid Arthritis

2021 ◽  
Vol 2021 ◽  
pp. 1-4
Author(s):  
Yoshifumi Tada ◽  
Nobuyuki Ono ◽  
Syuichi Koarada
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Certolizumab Pegol ◽  
Skin Lesions ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Drug Induced ◽  
Beneficial Effects ◽  
Disease Modifying ◽  
Disease Modifying Antirheumatic Drug

Biological disease-modifying antirheumatic drugs (bDMARDs) are very effective for treating rheumatoid arthritis (RA). However, they sometimes induce adverse events such as psoriasis-like skin lesions. We describe psoriasis-like skin lesions that developed simultaneously with an RA flare in patient 1 during treatment with abatacept and in patient 2 soon after starting certolizumab pegol. The skin lesions persisted in patient 2 despite stopping certolizumab. Baricitinib was initiated because of RA flare and resulted in immediate beneficial effects on arthritis as well as skin lesions. The RA went into remission in both patients, and the psoriasis-like skin lesions disappeared within four weeks (patient 1) and three months (patient 2).

scholarly journals Impact of disease-modifying antirheumatic drugs on vaccine immunogenicity in patients with inflammatory rheumatic and musculoskeletal diseases

2021 ◽  
Vol 80 (10) ◽  
pp. 1255-1265 ◽  
Author(s):  
Marcia A Friedman ◽  
Jeffrey R Curtis ◽  
Kevin L Winthrop
Keyword(s):  
Musculoskeletal Diseases ◽  
Janus Kinase ◽  
Vaccine Response ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Substantial Impact ◽  
Vaccination Recommendations ◽  
Increased Risk ◽  
Disease Modifying ◽  
Vaccine Immunogenicity

Patients with rheumatic diseases are at increased risk of infectious complications; vaccinations are a critical component of their care. Disease-modifying antirheumatic drugs may reduce the immunogenicity of common vaccines. We will review here available data regarding the effect of these medications on influenza, pneumococcal, herpes zoster, SARS-CoV-2, hepatitis B, human papilloma virus and yellow fever vaccines. Rituximab has the most substantial impact on vaccine immunogenicity, which is most profound when vaccinations are given at shorter intervals after rituximab dosing. Methotrexate has less substantial effect but appears to adversely impact most vaccine immunogenicity. Abatacept likely decrease vaccine immunogenicity, although these studies are limited by the lack of adequate control groups. Janus kinase and tumour necrosis factor inhibitors decrease absolute antibody titres for many vaccines, but do not seem to significantly impact the proportions of patients achieving seroprotection. Other biologics (interleukin-6R (IL-6R), IL-12/IL-23 and IL-17 inhibitors) have little observed impact on vaccine immunogenicity. Data regarding the effect of these medications on the SARS-CoV-2 vaccine immunogenicity are just now emerging, and early glimpses appear similar to our experience with other vaccines. In this review, we summarise the most recent data regarding vaccine response and efficacy in this setting, particularly in light of current vaccination recommendations for immunocompromised patients.

scholarly journals Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2013 update of the EULAR recommendations for the management of rheumatoid arthritis

2014 ◽  
Vol 73 (3) ◽  
pp. 516-528 ◽  
Author(s):  
Jackie L Nam ◽  
Sofia Ramiro ◽  
Cecile Gaujoux-Viala ◽  
Kaoru Takase ◽  
Mario Leon-Garcia ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Literature Review ◽  
Systematic Literature Review ◽  
Initial Treatment ◽  
Certolizumab Pegol ◽  
Treatment Strategies ◽  
Treat To Target ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Disease Modifying

ObjectivesTo update the evidence for the efficacy of biological disease-modifying antirheumatic drugs (bDMARD) in patients with rheumatoid arthritis (RA) to inform the European League Against Rheumatism(EULAR) Task Force treatment recommendations.MethodsMedline, Embase and Cochrane databases were searched for articles published between January 2009 and February 2013 on infliximab, etanercept, adalimumab, certolizumab-pegol, golimumab, anakinra, abatacept, rituximab, tocilizumab and biosimilar DMARDs (bsDMARDs) in phase 3 development. Abstracts from 2011 to 2012 American College of Rheumatology (ACR) and 2011–2013 EULAR conferences were obtained.ResultsFifty-one full papers, and 57 abstracts were identified. The randomised controlled trials (RCT) confirmed the efficacy of bDMARD+conventional synthetic DMARDs (csDMARDs) versus csDMARDs alone (level 1B evidence). There was some additional evidence for the use of bDMARD monotherapy, however bDMARD and MTX combination therapy for all bDMARD classes was more efficacious (1B). Clinical and radiographic responses were high with treat-to-target strategies. Earlier improvement in signs and symptoms were seen with more intensive initial treatment strategies, but outcomes were similar upon addition of bDMARDs in patients with insufficient response to MTX. In general, radiographic progression was lower with bDMARD use, mainly due to initial treatment effects. Although patients may achieve bDMARD- and drug-free remission, maintenance of clinical responses was higher with bDMARD continuation (1B), but bDMARD dose reduction could be applied (1B). There was still no RCT data for bDMARD switching.ConclusionsThe systematic literature review confirms efficacy of biological DMARDs in RA. It addresses different treatment strategies with the potential for reduction in therapy, particularly with early disease control, and highlights emerging therapies.

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