Table 1.

Recommendations for the initial treatment of patients with active psoriatic arthritis who are OSM- and other treatment–naive (PICOs 9–15)^*

	Level of evidence (evidence [refs.] reviewed)†
In OSM- and other treatment–naive patients with active PsA,
1. Treat with a TNFi biologic over an OSM (MTX, SSZ, LEF, CSA, or APR) (PICO 10a–e)	Low (53–66)
Conditional recommendation based on low-quality evidence; may consider an OSM if the patient does not have severe PsA,‡ does not have severe psoriasis,§ prefers oral therapy, has concern over starting a biologic as the first therapy, or has contraindications to TNFi biologics, including recurrent infections, congestive heart failure, or demyelinating disease.
2. Treat with a TNFi biologic over an IL-17i biologic (PICO 14)	Very low
Conditional recommendation based on very-low-quality evidence; may consider an IL-17i biologic if the patient has severe psoriasis or has contraindications to TNFi biologics, including recurrent infections, congestive heart failure, or demyelinating disease.
3. Treat with a TNFi biologic over an IL-12/23i biologic (PICO 13)	Very low
Conditional recommendation based on very-low-quality evidence; may consider an IL-12/23i biologic if the patient has severe psoriasis, prefers less frequent drug administration, or has contraindications to TNFi biologics, including recurrent infections, congestive heart failure, or demyelinating disease.
4. Treat with an OSM over an IL-17i biologic (PICO 12)	Very low
Conditional recommendation based on very-low-quality evidence; may consider an IL-17i biologic if the patient has severe psoriasis and/or severe PsA.
5. Treat with an OSM over an IL-12/23i biologic (PICO 11)	Very low
Conditional recommendation based on very-low-quality evidence; may consider an IL-12/23i biologic if the patient has concomitant IBD and/or severe psoriasis and/or severe PsA or prefers less frequent drug administration.
6. Treat with MTX over NSAIDs (PICO 9)	Very low (67)
Conditional recommendation based on very-low-quality evidence; may consider NSAIDs before starting MTX in patients with less active disease, after careful consideration of cardiovascular risks and renal risks of NSAIDs.
7. Treat with an IL-17i biologic over an IL-12/23i biologic (PICO 15)	Very low
Conditional recommendation based on very-low-quality evidence; may consider an IL-12/23i biologic if the patient has concomitant IBD or prefers less frequent drug administration.

^*Active psoriatic arthritis (PsA) is defined as disease causing symptoms at an unacceptably bothersome level as reported by the patient, and judged by the examining clinician to be due to PsA based_on ≥1 of the following: swollen joints, tender joints, dactylitis, enthesitis, axial disease, active skin and/or nail involvement, and extraarticular inflammatory manifestations such as uveitis or inflammatory bowel disease (IBD). Oral small molecules (OSMs) are defined as methotrexate (MTX), sulfasalazine (SSZ), leflunomide (LEF), cyclosporine (CSA), or apremilast (APR) and do not include tofacitinib, which was handled separately since its efficacy/safety profile is much different from that of other OSMs listed above. OSM- and other treatment–naive is defined as naïve to treatment with OSMs, tumor necrosis factor inhibitors (TNFi,) interleukin-17 inhibitors (IL-17i), and IL-12/23i; patients may have received nonsteroidal antiinflammatory drugs (NSAIDs), glucocorticoids, and/or other pharmacologic and nonpharmacologic interventions.

^†When there were no published studies, we relied on the clinical experience of the panelists, which was designated very-low-quality evidence.

^‡Because there are currently no widely agreed-upon definitions of disease severity, PsA severity should be established by the health care provider and patient on a case-by-case basis. For the purposes of these recommendations, severity is considered a broader concept than disease activity in that it encompasses the level of disease activity at a given time point, as well as the presence of poor prognostic factors and long-term damage. Examples of severe PsA disease include the presence of ≥1 of the following: a poor prognostic factor (erosive disease, elevated levels of inflammation markers such as C-reactive protein or erythrocyte sedimentation rate attributable to PsA), long-term damage that interferes with function (e.g., joint deformities, vision loss), highly active disease that causes major impairment in quality of life (i.e., active psoriatic inflammatory disease at many sites [including dactylitis, enthesitis] or function-limiting inflammatory disease at few sites), and rapidly progressive disease.

^§Because there are currently no widely agreed-upon definitions of disease severity, psoriasis severity should be established by the health care provider and patient on a case-by-case basis. In clinical trials, severe psoriasis has been defined as a Psoriasis Area and Severity Index (PASI) score (25) of ≥12 and a body surface area score of ≥10. In clinical practice, however, the PASI tool is not standardly utilized given its cumbersome nature. In 2007, the National Psoriasis Foundation published an expert consensus statement, which defined moderate-to-severe disease as a body surface area of ≥5% (68). In cases in which the involvement is in critical areas, such as the face, hands or feet, nails, intertriginous areas, scalp, or where the burden of the disease causes significant disability or impairment of physical or mental functioning, the disease can be severe despite the lower amount of surface area of skin involved. The need to factor in the unique circumstances of the individual patient is of critical importance, but this threshold provides some guidance in the care of patients.