Priority 8 from the Psoriatic Arthritis PSP

UNCERTAINTY: What are the long-term risks and benefits of medications used for psoriatic arthritis?  (JLA PSP Priority 8)
Overall ranking 8
JLA question ID 0108/8
Explanatory note People living with psoriatic arthritis and the healthcare professionals looking after them can often worry about the long-term risks the medications may cause to someone's general health. These are examples of some of these concerns that were submitted. Will the long-term usage of biologics that allow you to stay more mobile adversely affect you as you get older? Can some biologic medications make psoriasis worse? How long can you safely take biologic drugs?  There is a recognised need to expand and further develop this evidence base. Particularly for people who take multiple medications for psoriatic arthritis and other health complaints.

This question has been partially addressed in the evidence base from the following systematic reviews and guidelines:
**Coates, 2012. Key recommendations from the guidelines with reference to the management algorithm for considering using anti-TNF drugs in patients with PsA for both peripheral and axial disease
Venegas-Iribarren, 2018. Ustekinumab leads to clinical improvement in psoriatic arthritis, and probably is not associated to severe adverse effects
Vaengeberg, 2020. Data on cancer in patients with psoriatic arthritis remain scarce, and further research is warranted in this area.
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
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
Reygaerts, 2018. Biological disease modifying antirheumatic drugs and apremilast had a small effect on fatigue at 24 weeks in psoriatic arthritis randomized controlled trials and a higher effect on pain. These results are important to take into account in shared decision-making
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
Holroyd, 2019. DMARD safety guidelines in inflammatory arthritis. Biologics covered by this guideline are as follows: anti-TNF inhibitors: infliximab (IFX); etanercept (ETN); adalimumab (ADA); certolizumab pegol; golimumab; anti-CD20: rituximab (RTX); CTLA4-Ig: abatacept (ABA); anti-IL-6 receptor: tocilizumab (TCZ); and anti-IL-12/IL-23: ustekinumab. Recommendation: The decision to initiate a biologic should be made in conjunction with the patient/carer and initiated by an expert in the management of rheumatic disease. Patients should be assessed for co-morbidities as these may influence biologic choice, including evaluation for respiratory disease and screening for infection
Iragorri, 2018. Treatment with infliximab, golimumab, certolizumab pegol, ustekinumab, and apremilast resulted in improvements in self-reported work productivity. A pooled analysis was not possible because of the clinical heterogeneity of the trials and variability in outcome reporting
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
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
Finelli, 2021. Systematic review of studies reporting semen analysis, evaluation of seminal oxidative stress, and/or sperm DNA fragmentation in patients affected by psoriasis and psoriatic arthritis, celiac disease, inflammatory bowel diseases, systemic lupus erythematosus, ankylosing spondylitis, hidradenitis suppurativa, uveitis, dermatomyositis, and rheumatoid arthritis. Evidence suggested that various autoimmune diseases or relevant medications can adversely affect male fertility parameters and that patients may benefit of counseling and sperm cryopreservation. Clinical trials further investigating any adverse effect of autoimmunity and related thereby on male infertility are warranted, to develop appropriate guidelines for males diagnosed and treated for autoimmune disorders
Dai, 2019. Leflunomide is an effective and well-tolerated treatment for PsA, and would be a safe and convenient option

Health Research Classification System category Inflammatory and immune system
Extra information provided by this PSP
Original uncertainty examples How long can you safely take biologic drugs? 
Submitted by 34 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