Table 6.

Recommendations for treatment of patients with active psoriatic arthritis and comorbidities, including concomitant diabetes and recurrent serious infections (PICOs 63–66)^*

	Level of evidence (evidence [refs.] reviewed) †
In adult patients with active PsA and diabetes who are both OSM- and biologic treatment–naive,‡
1. Start an OSM other than MTX over a TNFi biologic (PICO 63a)	Very low (118, 119)
Conditional recommendation based on very-low-quality evidence; may consider starting a TNFi, if the patient has severe PsA§ or severe/active skin disease,¶ when diabetes is well controlled.
In adult patients with active PsA and frequent serious infections who are both OSM- and biologic treatment–naive,
2. Start an OSM over a TNFi biologic (PICO 64)	Moderate (33, 120)
Strong recommendation supported by moderate-quality evidence, including a black box warning against the use of a TNFi biologic with regard to increased risk of serious infection.
3. Start an IL-12/23i biologic over a TNFi biologic (PICO 65)	Very low (33)
Conditional recommendation based on very-low-quality evidence; may consider starting a TNFi if the patient has severe PsA.
4. Start an IL-17i biologic over a TNFi biologic (PICO 66)	Very low
Conditional recommendation based on very-low-quality evidence; may consider starting a TNFi biologic in patients with concomitant IBD.

^*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).

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

^‡Oral small molecules (OSMs) are defined as methotrexate (MTX), sulfasalazine, leflunomide, cyclosporine, or apremilast 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 naive 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, glucocorticoids, and/or other pharmacologic and nonpharmacologic interventions.

^§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.