Prescribe adalimumab.

Psoriatic arthritis (PsA) is an inflammatory, seronegative, human leukocyte allele-B27 (HLA-B27) associated spondyloarthropathy. The exact prevalence of PsA is controversial, but estimates vary from 0.3% to 1.0% (Gladman et al. 2005). Among patients with psoriasis, the prevalence of coexisting PsA varies significantly from 6% to 42% (Gottlieb et al. 2008). Patients with PsA often have a family history of psoriasis or PsA. Some studies indicate up to 39% of patients with PsA are HLA-B27 carriers (Queiro et al. 2016). Patients with PsA can present with tenderness, stiffness, reduced range of motion, and swelling of the affected joints. Any joint can be affected; however, PsA has a predilection to affect the distal joints of the upper and lower extremities. Involvement of the sacroiliac, wrist, knee, or ankle joints is also possible. Classically, the patient will experience prolonged morning stiffness with symptoms that are worse at rest and alleviated with activity. In a large clinical trial, 84% of patients with PsA had cutaneous psoriasis for a mean of 12 years before clinically recognized PsA (Gottlieb et al. 2006).

The distribution and extent of joint inflammation in PsA can differ considerably. Patients can develop peripheral arthritis, skin and nail disease, axial disease, dactylitis, or enthesitis. The course and severity of PsA can range from mild and nondestructive to severe with debilitating destruction of joints. The severity of skin disease and arthritis do not necessarily correlate with each other (Cohen et al. 1999). Nail changes or dystrophy is commonly found in patients with PsA. Studies have shown that 40–60% of patients with PsA develop erosive and deforming arthritis. If left untreated, patients will develop severe physical limitations and reduced quality of life. Characteristic radiographic findings of PsA include joint erosions, joint space narrowing, periosteal reaction, joint lysis, ankylosis, spur formation, and spondylitis. Dactylitis is common in PsA and can indicate a greater degree of radiologic damage (Brockbank et al. 2005). The time from arthritis symptom onset to radiographic evidence of disease varies considerably. Kane et al. demonstrated that joint erosions were present in 27% of patients at initial assessment and in 47% of patients at 2-year follow-up (Kane et al. 2003).

Tumor necrosis factor (TNF) inhibitors have proven to be a viable treatment option in the management of PsA. The efficacy of adalimumab was demonstrated in the ADEPT trial, a double-blind randomized controlled trial. At the conclusion of the 24-week study, adalimumab was found be effective in reducing the symptoms of arthritis and inhibiting the progression of structural changes seen on radiographs. By week 24 57% of patient receiving adalimumab achieved a 20% improvement in tender joint counts as well as a 20% improvement in three of five other criteria mandated by the American College of Rheumatology (ACR20). Likewise, the ACR50 and ACR70 response rates were 39% and 23%, respectively (Mease et al. 2005). Similar response rates were observed in the 48-week open-label extension (Gladman et al. 2007). Their study also demonstrated sustained inhibition of radiographic disease progression.

Patients with PsA were randomized to receive etanercept or placebo for 24 weeks. Fifty-nine percent of patients in the etanercept group achieved ACR20 at week 12 (Mease et al. 2004). In the open-label 48-week extension, the majority of patients who received etanercept sustained or improved their clinical response. Additionally, patients who were initially in the placebo arm and switched to receive etanercept exhibited a similar response to therapy. Imaging analysis of the hands and wrists demonstrated inhibition of radiographic disease progression. The PRESTA (Psoriasis Randomized Etanercept STudy in Subjects with Psoriatic Arthritis) trial documented significant reduction in the number of participants with dactylitis and enthesitis (Sterry et al. 2010).

A double-blind trial evaluating the efficacy of infliximab in 200 patients with active PsA showed a considerable improvement in ACR20 response at week 14. ACR50 and ACR70 responses continued to improve throughout the 24-week study (Antoni et al. 2005). A significant proportion of patients with dactylitis and enthesitis at baseline experienced improvement. At the conclusion of a 2-year study, 62% of patients maintained an ACR20 response (Antoni et al. 2008). Additional studies have shown radiographic evidence of infliximab preventing disease progression (Kavanaugh et al. 2006).

Two double-blind, multicenter, controlled trials demonstrated that patients who received ustekinumab for PsA experienced clinically meaningful improvements in physical function and health-related quality of life (Rahman et al. 2016). The first study included 615 biologic naïve patients with active PsA from 104 sites (PSUMMIT 1). Patients were randomized to receive 45 mg ustekinumab, 90 mg ustekinumab, or placebo. Of the three groups, 42%, 50%, and 23% of patients achieved ACR20 at week 24, respectively (McInnes et al. 2013). The majority of participants reported improvements in dactylitis and enthesitis and maintained an ACR20 response through week 100 (Kavanaugh et al. 2015a, b). Of note, despite the limitations of cross-study comparisons, ustekinumab appears to have a longer time to maximum effect when compared to TNF inhibitor studies. The second study (PSUMMIT 2) had efficacy findings that were consistent with the PSUMMIT 1 study. However, more than half of the participants had previously discontinued a TNF inhibitor due to lack of efficacy or intolerance (Ritchlin et al. 2014). In both studies, patients treated with ustekinumab had significantly less evidence of joint damage and disease progression on radiography when compared to placebo (Kavanaugh et al. 2014a, b).

Two double-blind, phase 3 studies were conducted to evaluate the efficacy of secukinumab in patients with psoriatic arthritis. The first study (FUTURE 1) observed 606 participants for 104 weeks. At week 24, among the patients who were biologic-naïve, 54.5% of patients who received 150 mg of secukinumab achieved ACR20 response (Mease et al. 2015). A lower (39%) ACR20 response was seen among patients with prior exposure to TNF inhibitors. At week 104, 67% of patients achieved ACR20 response (Kavanaugh et al. 2016). Eighty-four percent of patients did not show radiographic disease progression. Of note, there was no significant difference in ACR20 response rates in patients who were using methotrexate simultaneously. At the conclusion of the second study (FUTURE 2), the ACR20 response rate was 51% in patients who received 150 mg of secukinumab for 24 weeks (McInnes et al. 2015). Similar to the FUTURE 1 study, response rates were higher in the TNF inhibitor naïve group compared to the group with prior TNF inhibitor exposure.

Methotrexate is considered to be a second-line agent in the treatment of PsA. There is an insufficient amount of evidence demonstrating the efficacy of methotrexate in PsA (Ravindran et al. 2008). A randomized placebo-controlled trial with 221 patients found no statistically significant evidence that methotrexate improves any rheumatology-related response indices in PsA (Kingsley et al. 2012). Additionally, there was no observed benefit on objective measures of synovitis (joint counts, ESR, and CRP levels). However, methotrexate did seem to improve subjective symptom assessments. A study comparing the effectiveness of TNF inhibitors and methotrexate showed that disease activity and clinical improvement were significantly larger in the TNF inhibitor group (Heiberg et al. 2007). Of note, many randomized controlled trials studying biologic agents allow the concomitant use of methotrexate during study participation. The majority of the studies have not documented a significant difference in ACR20 response rates in patients taking a biologic in combination with methotrexate and patients taking a biologic alone (Combe et al. 2016).

Apremilast is also considered to be a second-line agent in the management of PsA. At week 16 in the PALACE 1 study, 40% of patients who received apremilast 30 mg BID achieved ACR20 (Kavanaugh et al. 2014a, b). The 24-week analysis showed similar results. A dose-related effect was observed with higher clinical response in patients receiving 30 mg BID compared to 20 mg BID. Similar to biologic studies, biologic-naïve patients had higher ACR20 response rates compared to patients with prior exposure to biologics. In the 52-week follow-up of the PALACE 1 study, 55% of patients receiving apremilast 30 mg BID achieved an ACR20 response (Kavanaugh et al. 2015a, b). However, only 25% and 14% of patients achieved ACR50 and ACR70, respectively. Improvements from baseline enthesitis and dactylitis were also noted. Efficacy results from the PALACE 2 study showed 53% of patients achieving ACR20 response at week 52 (Cutolo et al. 2016). Similar to PALACE 1, there was a significant decline in ACR50 and ACR70 response rates. The progression of radiographic joint damage has not been documented.