scholarly journals Pharmacological treatment of psoriatic arthritis: a systematic literature review for the 2015 update of the EULAR recommendations for the management of psoriatic arthritis

2015 ◽  
Vol 75 (3) ◽  
pp. 490-498 ◽  
Author(s):  
Sofia Ramiro ◽  
Josef S Smolen ◽  
Robert Landewé ◽  
Désirée van der Heijde ◽  
Maxime Dougados ◽  
...  

ObjectiveTo update the evidence on the efficacy and safety of pharmacological agents in psoriatic arthritis (PsA).MethodsSystematic literature review of randomised controlled trials comparing pharmacological interventions in PsA: non-steroidal anti-inflammatory drugs, glucocorticoid, synthetic disease modifying antirheumatic drugs (sDMARDs) either conventional or targeted, biologicals (bDMARDs), placebo or any combination. Main outcomes were American College of Rheumatology (ACR)20–50, Psoriasis Area Severity Index 75, radiographic progression, and withdrawals due to adverse events (AEs). Multiple studies of the same intervention were meta-analysed using random effects.ResultsIn total, 25 papers and 12 abstracts were included. The efficacy of tumour necrosis factor inhibitors (including the recently added golimumab and certolizumab pegol) was confirmed and 16 articles/abstracts focused on 3 drugs with new modes of action: ustekinumab (UST), secukinumab (SEC) and apremilast (APR). All were placebo-compared trials and met their primary end point, ACR20. In 2 studies with UST ACR20 was met by 50% and 44% of patients with UST 90 mg, 42% and 44% with UST 45 mg vs 23% and 20% with placebo, respectively. In two studies with SEC ACR20 ranged 54% (SEC 300 mg), 50–51% (SEC 150 mg), 29–51% (SEC 75 mg) and 15–17% (placebo). In four studies with APR, ACR20 ranged 32–43% (APR 30 mg), 29–38% (APR 20 mg) and 17–20% (placebo). For all three drugs, no more withdrawals due to AEs than placebo were seen and, in general, safety appeared satisfactory. A strategy trial, TIght COntrol of Psoriatic Arthritis (TICOPA), showed better ACR responses with treatment adaptations upon tight control compared with standard care.ConclusionsUST, SEC and APR are new drugs with efficacy demonstrated for the treatment of PsA. No major safety signals arise, but long-term studies are needed. This review informed about the European League Against Rheumatism recommendations for management of PsA.

2017 ◽  
Vol 76 (6) ◽  
pp. 1102-1107 ◽  
Author(s):  
Katerina Chatzidionysiou ◽  
Sharzad Emamikia ◽  
Jackie Nam ◽  
Sofia Ramiro ◽  
Josef Smolen ◽  
...  

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.


2014 ◽  
Vol 73 (3) ◽  
pp. 529-535 ◽  
Author(s):  
Sofia Ramiro ◽  
Cécile Gaujoux-Viala ◽  
Jackie L Nam ◽  
Josef S Smolen ◽  
Maya Buch ◽  
...  

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.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 957-957
Author(s):  
N. M. T. Roodenrijs ◽  
A. Hamar ◽  
M. Kedves ◽  
G. Nagy ◽  
J. M. Van Laar ◽  
...  

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


2017 ◽  
Vol 20 (9) ◽  
pp. A533
Author(s):  
C Rubio-Terrés ◽  
D Rubio-Rodrígues ◽  
S Grau ◽  
R Blanco ◽  
JD Sanchez ◽  
...  

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