Priority 10 from the Psoriatic Arthritis PSP

UNCERTAINTY: What treatments present the most benefit (considering efficacy, tolerability and safety) for the different body tissues involved in psoriatic arthritis, for example, joints, tendons, spine, skin and nails? (JLA PSP Priority 10)
Overall ranking 10
JLA question ID 0108/10
Explanatory note Because psoriatic arthritis can affect multiple different tissues in the body it is important to know which treatments help the most with specific problems. For example, for joints, for nails or for skin. For example, what medications are most useful for joint pain and skin psoriasis? What are the best medications for enthesitis? What treatments are best for nails? What is the best way to treat the back and neck when they are involved? 

This question has been partially addressed in the evidence base from the following systematic reviews and guidelines:
**Coates, 2012. Safety recommendations made for using patients considering anti-TNF medication who have tuberculosis, HIV, hepatitis, maligancy and who are pregnant
Abdelghani, 2020. A review of rheumatic inflammatory diseases including PsA. Limited evidence to suggest US-guided injection in retroclacneal bursistis with a lateral approach was beneficial in terms of preventing side effects
Venegas-Iribarren, 2018. Ustekinumab leads to clinical improvement in psoriatic arthritis, and probably is not associated to severe adverse effects
Torres, 2021. Evidence for psoriatic disease (including psoriasis and peripheral arthritis. Secukinumab and ixekizumab were the treatments with the highest probability of reaching both PASI100 and ACR70 outcomes. Due to the lack of a standard evaluation of outcomes of the other psoriatic disease domains, a network meta-analysis for all the domains was not possible to perform
Bilal, 2018. Our meta-analysis shows that the inhibitors of IL-6 (clazakizumab), IL-12/23 (ustekinumab), and IL-17A (secukinumab, brodalumab, ixekizumab) are efficacious and generally well tolerated when used to treat patients with PsA
Ruyssen-Witrand, 2020. Network meta-analysis confirms the efficacy and acceptable safety profile of bDMARDs in patients with active PsA. There were generally few statistically significant differences between most treatments
Qui, 2020. Direct and indirect comparisons and integrated results suggested that the 3 anti- tumor necrosis factor -α biologics (GOL, ETN, and IFX) can be considered the best treatments for PsA after comprehensive consideration of efficacy and safety
Ruhoff, 2019. Clinical benefits have been found in the treatment of PsA with Methotrexate (MTX). MTX has demonstrated clinical efficacy in the treatment of psoriasis; however, the treatment of peripheral arthritis still lacks supportive evidence. More controlled trials need to be conducted to underpin evidence-based use of MTX
Mourad, 2020. The pooled analysis demonstrated that anti-TNF-α agents have the same efficacy as novel agents (ustekinumab, secukinumab, and ixekizumab) in dactylitis and enthesitis
McInnes, 2018. Secukinumab demonstrated good efficacy across all outcomes. All treatments for active PsA included in this comprehensive network meta-analysis demonstrated superiority to placebo across full-study populations, biologic-naive patients and biologic-experienced patients
Kaely, 2020. Factors that affected responsiveness in clinical trials included the entheseal instrument used, the number of subjects available for comparison, as well as the therapeutic agent. In general, anti-TNF and anti-IL-17 agents, as well as Janus kinase inhibitors, show moderate responsiveness for enthesitis. The data for IL-23 targeting is contradictory
Huang, 2019. Both dosages of tofacitinib (5mg and 10mg) were safe to use. Even if similar adverse drug events were observed with 5 mg versus 10 mg tofacitinib twice daily for the treatment of autoimmune disorders, anemia was more prominent with 10 mg tofacitinib at a 3 month follow-up. Further research needed
Gratacos Masmitja, 2020. Ofacitinib has been demonstrated to be efficacious for the treatment of peripheral and axial involvement, enthesitis, and dactylitis manifestation in PsA. Further research needed
Gladman, 2020. Tofacitinib provides an additional treatment option for patients with psoriatic arthritis, both in patients naïve to TNFi and in those with TNFi-IR
NICE, 2018. Ixekizumab (Taltz) is available on the NHS as a possible treatment for active psoriatic arthritis in adults:
1. With at least 3 tender and 3 swollen joints who have already tried at least 2 disease-modifying antirheumatic drugs given on their own or together, but they haven’t worked or 2. Who have had a tumour necrosis factor (TNF)‑alpha inhibitor but this hasn’t worked well enough within 12 weeks or after 12 weeks of treatment or 3.When TNF-alpha inhibitors would be used but the person cannot have them. Only people whose psoriatic arthritis improves enough by 16 weeks may carry on with treatment. Ixekizumab can be taken alone or with a drug called methotrexate
NICE, 2018. Tofacitinib (Xeljanz), taken with a drug called methotrexate, is available on the NHS. It is a possible treatment for active psoriatic arthritis in adults: With at least 3 tender and 3 swollen joints, who have already tried at least 2 disease-modifying antirheumatic drugs given on their own or together, but they haven’t worked or, who have had a tumour necrosis factor (TNF)-alpha inhibitor but this hasn’t worked well enough within 12 weeks or after 12 weeks of treatment or, when TNF-alpha inhibitors would be used but the person cannot have them. Only people whose psoriatic arthritis improves enough by 12 weeks may carry on with treatment
Dressler, 2019. For ACR20/50, HAQ-DI and SF-36, the active treatment was efficacious and the quality of the evidence was mostly moderate to low (15 of 18 comparisons). The quality of evidence for (serious) adverse events was mostly low; differences were rare. In three placebo-controlled comparisons, leflunomide, MTX and sulfasalazine failed to show statistical superiority for ACR. Besides the established treatment of anti-TNF antibodies and ustekinumab for psoriatic arthritis, the newer treatment options of IL17 antibodies and apremilast are also effective for the treatment of psoriatic arthritis. Based on just one comparative trial and one drug each, the new class of anti-IL 17 antibodies appears to be equally effective as the group of anti-TNF antibodies; for apremilast, this is yet unclear
Dai, 2019. Leflunomide is an effective and well-tolerated treatment for PsA, and would be a safe and convenient option
D'Angiolella, 2018. Biologic therapies are more effective than disease-modifying anti-rheumatic drugs for the symptoms and signs of psoriatic arthritis and for improving quality of life and inhibiting structural radiological damage. Therefore, biologic therapies are cost effective compared with conventional therapies: the increased direct cost associated with biologic drugs is offset by the significant improvement in the efficacy of treatments and in patient management of psoriatic arthritis
Tahir, 2018. Golimumab was found to be clinically effective and also have a good safety profile in the treatment of RA, PsA, and AS based on data available from large studies
Champs, 2019. 77 randomised controlled studies did not reveal any significant change in the short-term risk of MACE or CHF in patients with PsA or psoriasis initiating a biological therapy
Balsa, 2018. Observations in other rheumatic diseases, the incidence of anti-drug antibodies formation to biologic agents in patients with PsA is often decreased when patients are given concomitant treatment with disease-modifying anti-rheumatic drugs. These data strongly suggest that the immune response is a characteristic of the biologic agent. Using therapeutic drug monitoring may be an approach to assess the immune response to the agent and to mitigate the potential impact on efficacy and safety, and consequently optimise treatment
Luo, 2019. A significant positive association between therapy and increased risk for overall malignancy was found relative to the general population as the reference group. : This study allowed the estimation of cancer risk in PsA patients during therapy. Large-scale longitudinal studies will be essential to draw firm conclusions regarding PsA-associated risk for treatment-induced malignancy
Lu, 2019. The overall risk-benefit profile, infliximab, guselkumab, adalimumab, golimumab, secukinumab, and ustekinumab may be safer and more efficacious treatments than the other targeted DMARDs for active PsA during induction therapy
Loft, 2020. Biologics targeting interleukin (IL)-17 and IL-23 are generally well-tolerated and considered safe, though adverse events are seen more often compared with placebo. Across therapies, the most prevalent AEs were infections, nasopharyngitis and headache. For ixekizumab one of the most prevalent AEs was injection site reactions, reported in 15.7% of the patients after 52 weeks. Overall, IL-17 and IL-23 inhibitors appear to be well-tolerated with good safety profiles
Kawalec, 2018. No significant differences among non-anti-TNF-α biologics in the treatment of PsA in the comparisons performed with regards to the highest efficacy and safety. Both in the overall population and in the analyzed subpopulations, secukinumab 300 mg was ranked the highest for the ACR20 response rate. Secukinumab 300 mg was the safest drug in terms of any adverse events, and ustekinumab 90 mg presented the lowest overall risk of serious adverse events. Further studies needed
Kerschbaumer, 2020. Review of efficacy and safety of Janus kinase (JAK) inhibition in immune-mediated inflammatory diseases (IMIDs). Efficacy of JAKi was shown for tofacitinib (TOFA) and filgotinib (FILGO) in psoriatic arthritis
Knowles, 2020. A systematic review of studies examining effects of mono- clonal antibodies against TNFα on subclinical measures of arteriosclerosis and atherosclerosis in chronic inflammatory disease, including PsA. There is no strong evidence from randomised trials that anti-TNFα treatment causes durable improvement in such measures. TNFα antagonism could still have positive effects on clinical outcomes in this population through other mechanisms
Ureyen, 2018. There is evidence in the literature to guide clinicians on how to treat PsA patients with polyarticular disease, but there is a gap in knowledge about the other subtypes
Wu, 2018. Secukinumab may be the safest and most efficacious short-term treatment for peripheral PsA among all the new biologics targeting IL-6, IL-12/23 and IL-17 pathways
Simons, 2020. All bDMARDs showed higher ACR20 response rates and better HAQ-DI mean reduction compared to placebo. This meta-analysis highlights the variability of bDMARD efficacy on ACR50/70, PASI75/90 and enthesitis or dactylitis response rates. Head-to-head studies are needed to draw definitive conclusions on potential efficacy-related differences between bDMARDs in PsA
Maese, 2018. Review of efficacy of DMARDs in PsA. The studies included were not robust, and there are arguments to support the effectiveness of methotrexate, the evidence observed with the treatment of DMARDs in PsA is not conclusive. Further research needed
Luttropp, 2019. Systematic review of immune-mediated rheumatic diseases including PsA. Golimumab persistence at 24 months approximates 50%, with a lower persistence among AxSpA (43%) patients. However, as the number of studies in these populations was low, they warrant further research. In 12 studies comparing various TNFi treatments, golimumab was shown to have significantly better or equal persistence to its comparators
Song, 2019. In patients with active psoriatic arthritis, tofacitinib 10 mg and apremilast 30 mg were the most efficacious interventions and were not associated with a significant risk of serious adverse events
Song, 2018. Assessed the relative efficacy and safety of apremilast, secukinumab, and ustekinumab at different doses in patients with active psoriatic arthritis (PsA). All drug treatments were more efficacious than placebo; however, there were no significant differences in the efficacy and safety between the drugs at the different doses

Health Research Classification System category Inflammatory and immune system
Extra information provided by this PSP
Original uncertainty examples What are the best treatments for enthesitis?  
Submitted by 45 uncertainties submitted 
PSP information
PSP unique ID 0108
PSP name Psoriatic Arthritis
Total number of uncertainties identified by this PSP. 46  (To see a full list of all uncertainties identified, please see the detailed spreadsheet held on the JLA website)
Date of priority setting workshop 12 July 2021