Introduction
Background and definition
Purpose, aim, and scope
Target population, audience/end-users
Materials & methods
Results
Eligibility criteria for biological treatment
Monitoring for disease activity and assessment tools
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swollen joint count of 66 joints,
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tender joint count of 68 joints,
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patient’s global assessment on a 10 cm visual analogue score (VAS) (in cm): (0 for not active, up to 10 for very active)
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patient’s pain score on a 10 cm VAS (in cm): (0 for none up to 10 for very severe), and
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CRP (mg/dL).
DAPSA | MDA | ||
---|---|---|---|
Score | Interpretation | Criteria | Score |
≤ 4 | Remission | Tender joint count | ≤ 1 |
> 4 and ≤ 14 | Low disease activity | Swollen joint count | ≤ 1 |
> 14 and ≤ 28 | Moderate disease activity | PASI or BSA | ≤ 1 or ≤ 3 |
> 28 | High disease activity | Patient pain VAS | ≤ 15 |
Patient global activity VAS | ≤ 20 | ||
HAQ | ≤ 0.5 | ||
Tender entheseal points | ≤ 1 |
Treatment goals
Screening, precautions, and monitoring of biologics
Parameter | Baseline | Follow-upa |
---|---|---|
CBC with differential | ✓ | 3 to 6 months |
Creatinine | ✓ | 3 to 6 months |
Liver Enzymes (ALT, AST) | ✓ | 3 to 6 months |
Lipid profileb | ✓ | 3 to 6 months |
HBV/HCV HIVc | ✓ ✓ | - |
TST or IGRAd | ✓ | - |
Chest X-ray | ✓ | - |
bDMARDs and JAKi therapies for the treatment of severe PsA
Pharmacologic Category | Agent Name | Authority approval | Dosing in adults | Efficacy | Half life | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Loading | Maintenance | ACR50 | PASI 75 | MDA | Resolution of enthesitis | Resolution of dactylitis | vdHS | HAQ-DIe | ||||
TNFi | Adalimumaba [63] | SFDA: Yes FDA: Yes EMA: Yes | 40 mg SQ every other week | 32.6%e | 42.8%e | 38.7%e | 38%e | 77.8%e | 0.30e | -0.40 | 14 days | |
Certolizumab pegol [64] | SFDA: Yes FDA: Yes EMA: Yes | 400 mg SQ at week 0, 2and 4 | 200 mg SQ every 2 weeks or 400 mg every 4 weeks | 44%c | 62%c | 33.3%e | 64%e | NA | 0.41c | 0.41 | 14 days | |
Etanercept [65] | SFDA: Yes FDA: Yes EMA: Yes | 50 mg SQ once weekly | 25mg: 38.7%e | 25mg: 21.4%e | NA | 53%e | NA | 25mg:0.13e | NA | 3.5 days | ||
Infliximabb [66] | SFDA: Yes FDA: Yes EMA: Yes | 5 mg/kg IV for 2 h at 0, 2, and 6 weeks | 5 mg/kg IV for 2 h every 8 weeks | 39.8%d | 60%d | 58e | 53%c | 12e | -0.83c | -0.51 | 10 – 15 days | |
IL-17i | Secukinumab [67] | SFDA: Yes FDA: Yes EMA: Yes | 150 mg SQ at weeks 0, 1, 2, 3, and 4 | 150mg or 300 mg SQ every 4 weeks as needed | 150mg: 35%e 300mg: 39%e | 150mg:51.7%e 300mg:59.1%e | 150mg: 28%e 300mg:33%e | 150mg:54.6%e 300mg: 61%e | 150mg:63.7%e 300mg: 63.4% | 150 mg: 0.10e 300 mg: 0.27e | 150 mg: -0.48 300 mg: -0.56 | 27 days |
Ixekizumab [68] | SFDA: Yes FDA: Yes EMA: Yes | 160 mg SQ once at weeks 0 | 80 mg SQ every 4 weeks | 40%e | 61.3%e | 29.9%e | 42.6%e | 79.5%e | 0.37e | -0.44 | 13 days | |
IL-12/23i | Ustekinumab [69] | SFDA: Yes FDA: Yes EMA: Yes | 100 kg or less:45 mg SQ at 0 and 4 weeks Greater than 100 kg: 90 mg SQ at 0 and 4 weeks | 100 kg or less:45 mg SQ every 12 weeks Greater than 100 kg: 90 mg SQ every 12 | 45mg:20.2%e 90mg: 23.8%e | 45mg: 52.6%e 90mg: 57.3%e | NA | 36.2%e | 42.9e | NA | 45mg: -0.21 90mg: -0.22 | 21 days |
IL23i | Guselkumab [70] | SFDA: Yes FDA: Yes EMA: No | 100 mg SQ at weeks 0 and 4 | 100 mg SQ every 8 weeks | 33%e | 76.8%e | 25%e | 54%e | 59.4%e | 0.26e | -0.40 | 18 days |
IL23i | Risankizumab [34] | SFDA: Yes FDA: Yes EMA: Yes | 150 mg at weeks 0, 4 | 150 mg every 12 weeks | 33.4%e | 88.8%c | 25%e | 48.4e | 68.1%e | NA | -0.31 | 28 days |
JAKi | Tofacitinib | SFDA: Yes FDA: Yes EMA: Yes | 5 mg orally twice daily (IR tablet) or 11mg once daily (ER tablet) | 25%c | 32.2%c | 26%d | 33.3%e | 34.4%e | NA | -0.56 | ER: 6 – 8 h. IR: 3 h | |
Upadacitinib | SFDA: Yes FDA: Yes EMA: Yes | 15 mg once daily | 52.4%e | 62.6%d | 37%e | 53.7%e | 76.5%e | -0.04e | -0.47 | 8 – 14 h | ||
PDE4i | Apremilast [71] | SFDA: Yes FDA: Yes EMA: Yes | Day 1: 10 mg orally in AM Day 2: 10 mg twice daily Day 3: 10 mg in AM, 20 mg in PM Day 4: 20 mg twice daily Day 5: 20 mg in AM, 30 mg in PM | 30 mg orally twice dailyf | 13.7%d | 21.2%d | NA | NA | NA | NA | -0.26 | 6 – 9 h |
Treatment algorithm
Peripheral arthritis
Dactylitis and enthesitis
Axial PsA
Recommendations for the treatment of PsA with biological therapies
Adjusting/maintenance biological therapy
Combination
Biologic therapy discontinuation
Management of inadequate response
Use of bDMARDs and JAKi in special patient populations
Patient Population / Comorbidity | Recommendations |
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Infection | In the presence of serious active infections (defined as the need of intravenous antibiotics or hospitalization excluding TB, biologics should be avoided [47, 88] Biologics should be used with caution in patients at risk for severe infection after discussing the risks and benefits with the patients [47, 88] IL-17i may be considered, however, it is associated with increased risk of infection, particularly mucocutaneous Candida infection [72] |
Latent or reactivated TB | Patients with LTBI should be treated with anti-TB treatment at least 1 month before initiating biologic therapy and are to be monitored every 3 months during the treatment course [47, 88, 96‐98] |
Active TB | |
HBV and HCV | Biologics may be used safely in HBV positive after risk-benefit discussion made with a hepatologist and if appropriate antiviral treatment is given [47, 88, 106‐113] The use of TNFi in patients with HBV infection is not recommended due to risk of infection reactivation in comparison to other biologics (IL-12/23i, IL-17i, and IL-23i) [114] IL-17i, IL-23i, and JAKi appear to have a favorable safety profile with HBV, but the available data are limited [115, 116] Studies to date continue to show that biologics do not seem to have a detrimental effect on HCV infection (especially TNFi). However, a risk-benefit decision should be discussed with a hepatologist [117‐120] TNFi and IL-12/23i appear to be well tolerated in patients with HCV infection. However, IL-17i and IL-23i should be used with caution in patients with HCV due to the lack of available data [116] Apremilast can be considered as a treatment option for HBV and HCV [116] |
HIV | Decisions regarding start of biologics in HIV positive patients should be discussed with an HIV specialist [47, 88] |
Malignancy | In patients with a history of malignancy, it is recommended to discuss the decision to initiate immunosuppressive therapies, biologics, JAKi, and apremilast with the treating oncologist. The time of starting biologics post malignancy depends on multiple factors (type and stage of malignancy, risk of metastasis and patient’s characteristics) [47, 88] Although data shows that a considerable percentage of malignancy survivors initiated biologic therapy within 3 to 5 years post malignancy, risk and benefit should be discussed with the treating oncologist [121] |
Cardiovascular diseases | Biologics can be used in patients with history of myocardial infarction or other cardiovascular events [47, 88]. The use of TNFi, IL-17i and IL-12/23i does not seem to increase the risk of adverse cardiovascular outcomes [47, 88] TNFi, IL-17i, and IL12/23i are associated with improved cardiovascular risk in patients with PsA and therefore, they are suggested to be used in patients with concomitant ischemic heart disease [122] After ruling out other potential causes, discontinuation of TNFi is considered in patients with worsening heart failure with the cardiologist decision [47, 88]. JAKi may increase risk of cardiovascular disease in high-risk population and should be avoided in this population [124] |
Respiratory diseases | Biologics should be used with caution in patients with interstitial lung disease (ILD) with poor respiratory reserve with a close follow up with the pulmonologist [47, 88]. |
Uveitis | Monoclonal TNFi can be considered for the treatment of uveitis |
Demyelinating disease | Use of TNFi is contraindicated in patients with demyelinating diseases including Multiple Sclerosis (MS). Other non-TNFi biologics should be considered [47, 88]. In patients with a first degree relative with MS or other demyelinating disease, it is suggested to not use TNFi if other suitable treatment options are available [104, 123] Once demyelination develops while on TNFi, they should be discontinued and rechallenging with other TNFi is not recommended [16, 23] IL-17i can be considered in patients with demyelinating disease [125]. Data are limited for the IL-23i and JAKi, but there are no reports of MS worsening with these agents Patients with a history of concomitant MS might benefit from IL-12/23i therapy [72] |
Connective tissue disease | TNFi therapy should be discontinued if a lupus-like syndrome or other significant connective tissue diseases develops, and other non- TNFi biological agent should be considered [47, 88] There are not enough data regarding the use of IL-17i, IL-23i, and JAKi in this patient population [47, 88] IL-12/23i could be considered as a treatment option in patients with SLE [126] |
Obesity | Obesity can reduce TNFi efficacy, but a higher BMI has not been associated with a poor treatment response with IL-17i, IL12/23i, IL23i, or JAKi [127] |
Surgery | |
IBD | Patients with a history of concomitant IBD might benefit from monoclonal TNFi and IL-12/23i since they are effective in IBD. Moreover, IL-23i, and JAKi are suggested to be used in patients with PsA and IBD [72, 122] Decisions regarding optimal therapeutic agent should be discussed with a gastroenterologist [122] |
Pregnancy and lactation | Rheumatologists are expected to be familiar with drug safety during pregnancy and lactation to ensure that the disease is well controlled and to minimize the risks to both the mother and the infant. However, since the data regarding this field are derived from case reports, small series, and observational studies only, this area is still challenging to the treating clinicians The decision to initiate biologic therapy and treatment option should be determined on an individual basis based on risk management plans. TNFi could be considered as a treatment option in pregnancy [143] |
Paediatrics/adolescents | Juvenile psoriatic arthritis (JPsA) can have a diverse clinical presentation, with peripheral arthritis, dactylitis, enthesitis, as well as axial spondylitis. Disease activity is mainly measured clinically, as laboratory and radiographic tests might not be a timely indicator of disease progression [131, 132]. Disease pattern in younger age groups and females, usually has an oligoarticular pattern with or without dactylitis, while in older youth and males, enthesitis related disease and axial involvement is more common [133]. Uveitis has been more commonly reported with JPsA in comparison to psoriasis skin limited disease, which warrants regular screening [134, 135] Treatment recommendations for this group are pooled from JIA guidelines, although the subcategory of JPsA might require a more aggressive treatment [136]. Evidence for treatment choice is also gathered from adult clinical trials, while treatment choice is based on disease involvement similar to adults DMARDs are preferred over NSAIDs which can only be used temporarily, as they are not known to halt disease progression and achieve remission [137] MTX is recommended over leflunomide, specifically for arthritis, yet it has not shown good response for dactylitis. Similar to other JIA subtypes, Intra-articular corticosteroids injection can be considered for mono-arthritis and dactylitis [131, 138] Biological DMARDs are recommended in case of continued disease activity, where choice of biological therapy depends on disease involvement. TNFi are recommended for PsA, sacroiliitis, and dactylitis [139, 140] Secukinumab is indicated for the treatment of active PsA in patients 2 years of age and older. Tofacitiniba is used for the treatment of active JIA and JPsA in patients two years of age and older IL-23i and other JAKi are not yet approved for the use in pediatrics population but can be a promising option in peripheral and axial PsA [141] |
Vaccination | Timing of DMARD therapy with live vaccines should be taken in consideration [142] |