Treatment of psoriatic arthritis

INTRODUCTION — Effective treatment of psoriatic arthritis (PsA) requires coordinated intervention to address the major domains of the disease, including peripheral and axial arthritis, enthesitis, dactylitis, and skin and nail involvement.

The severity of involvement in each domain may range from mild to severe; some patients experience debilitating disease in one or more domains. Each of these domains must be evaluated independently in order to develop a comprehensive treatment regimen.

The care of a patient with PsA also requires evaluation of comorbid conditions, many of which negatively impact therapeutic response.

The treatment of axial arthritis, enthesitis, and dactylitis is discussed in this topic review. The treatment of peripheral arthritis, psoriatic skin and nail involvement, the clinical manifestations and diagnosis of PsA, the pathogenesis of PsA, and the safety of specific drugs during pregnancy and lactation are presented separately:

●(See "Treatment of psoriasis in adults".)

●(See "Nail psoriasis".)

●(See "Clinical manifestations and diagnosis of psoriatic arthritis".)

●(See "Pathogenesis of psoriatic arthritis".)

●(See "Treatment of peripheral psoriatic arthritis".)

●(See "Safety of rheumatic disease medication use during pregnancy and lactation".)

PRETREATMENT RECOMMENDATIONS — The approach to treatment includes therapy for both musculoskeletal disease and disease of the skin and nails. The goal of therapy is to control inflammation and prevent discomfort, joint damage, and disability [1,2]. Psoriatic arthritis (PsA) often affects multiple disease domains simultaneously.

Disease domains and treatment selection — Treatment is guided initially by an assessment of disease impact on each of the following domains:

●Peripheral arthritis

●Axial arthritis

●Dactylitis

●Enthesitis

●Skin

●Nails

For patients with multidomain involvement, we try to select a therapy that treats all the domains. If this is not possible, we focus on the domain that is most troubling to the patient. For example, we would suggest a tumor necrosis factor (TNF), interleukin 17 (IL-17), or Janus kinase (JAK) inhibitor in patients presenting with both peripheral and axial disease (figure 1). (See "Treatment of peripheral psoriatic arthritis".)

Importance of early treatment — Patients benefit from early intervention [3,4]. One study of 283 PsA patients demonstrated that those who saw a rheumatologist within six months of symptom onset had better radiographic and functional outcomes than patients seen later [3]. Similarly, another study found that patients who presented to a clinic specializing in the care of PsA within two years of diagnosis had less joint damage than those who presented later [4].

Treat-to-target approach — Therapies should be selected using a treat-to-target approach, in which treatments are adjusted every three months to achieve remission or low disease activity [5-7]. Application of a treat-to-target strategy to the management of PsA is a principle recommendation of an international task force for PsA and spondyloarthritis [6,7].

●Choice of target – The choice of the target should be tailored with the patient; low disease activity may be a more appropriate target in patients with longstanding disease or multiple comorbidities, in whom remission may be particularly difficult to achieve.

The choice of the target also depends on which disease domains are most relevant to the patient. For example, some patients are most concerned about controlling arthritis, while others are more focused on psoriasis even in the presence of active joint inflammation.

●Shared decision-making – Treatment choices should reflect the patient’s goals and preferences. For example, shared decision-making should be employed in selecting the treatment target. Patients may also have preferences regarding certain medications because of the route of administration and/or potential side effects. Shared decision-making can result in better adherence, improved patient outcomes, and reduced disease progression [8-11].

Shared decision-making requires that patients are educated regarding the nature of their condition and the effect of stress on their disease, as well as the importance of managing the cardiovascular risk associated with the disease and other comorbidities. (See "Clinical manifestations and diagnosis of psoriatic arthritis", section on 'Comorbidities' and "Comorbid disease in psoriasis".)

●Multispecialty coordination – Patients benefit from evaluation and treatment early in the disease by clinicians with expertise in the care of patients with rheumatologic conditions [3,4]. (See 'Prognosis' below.)

Treatment should be coordinated between a rheumatologist, primary care clinician, and relevant specialists (eg, dermatologist). Patients should be referred as needed for prevention and medical management of comorbid conditions. Many patients may not have a primary care clinician who can coordinate the patient’s care, in which case this role may need to be assumed by the rheumatologist.

Comorbidities — Comorbidities (eg, diabetes, metabolic syndrome, fatty liver, coronary artery disease, depression, hyperuricemia) are prevalent in PsA and should be identified because they can affect overall health and treatment selection.

●Cardiovascular risk factors – All patients should be screened for cardiovascular risk factors (eg, lipids, blood pressure, and smoking history).

In patients with elevated cardiovascular risk, JAK inhibitors should be prescribed with great caution following a detailed discussion with the patient regarding risks and benefits of these drugs based on data in rheumatoid arthritis populations [12]. (See "Overview of the Janus kinase inhibitors for rheumatologic and other inflammatory disorders", section on 'Cardiovascular'.)

●Obesity – Weight loss improves PsA outcomes in patients with obesity [13,14]. Patients with an elevated body mass index (BMI) should undergo weight-loss counseling and evaluation for nonalcoholic fatty liver disease and diabetes.

When relevant, patients should be referred for physical and occupational therapy, encouraged to exercise, referred as needed for orthotics, and educated about joint protection. (See "Exercise prescription and guidance for adults", section on 'Prescribing an exercise program' and "Obesity in adults: Overview of management", section on 'Approach to therapy'.)

In patients with obesity, intravenous biologic agents (eg, infliximab, golimumab) may be preferred over subcutaneous biologic agents, which may have variable absorption. In patients with diabetes, agents with a lower risk of infection such as apremilast, IL-23 or IL-12/23 inhibitors may be preferred.

●Anxiety and depression – Many patients suffer from anxiety and depression, disorders that may result in medication nonadherence and avoidance of systemic therapies.

In patients with severe anxiety and depression, apremilast and brodalumab should be avoided due to a potential association with suicidality.

PERIPHERAL ARTHRITIS — The management of the peripheral arthritis of psoriatic arthritis (PsA) is discussed separately. (See "Treatment of peripheral psoriatic arthritis".)

AXIAL DISEASE

Mild axial symptoms — In patients with mild symptoms of axial disease, which includes patients with inflammatory back pain that does not interfere with function, we suggest the use of nonsteroidal antiinflammatory drugs (NSAIDs) in antiinflammatory dose regimens, which may be at the higher end of the dosing range (eg, naproxen 375 to 500 mg twice daily, indomethacin 100 to 150 mg daily in divided doses, celecoxib 200 mg twice daily) (table 1).

NSAIDs can lessen pain and stiffness in spondylitis, although support for their use for axial manifestations of psoriatic arthritis (PsA) is based upon their demonstrated benefit in patients with ankylosing spondylitis, expert opinion, and clinical experience [1,2,15-17]. (See "Treatment of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'Initial drug therapy with NSAIDs'.)

Moderate to severe axial disease — In patients with axial symptoms that do not respond adequately to treatment with NSAIDs, such as those with prolonged morning stiffness and severe pain interfering with function, we recommend a tumor necrosis factor (TNF) or interleukin 17 (IL-17) inhibitor rather than a traditional nonbiologic disease-modifying antirheumatic drug (DMARD), as the latter have been shown to be ineffective for axial spondyloarthritis [18-20]. (See "Treatment of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'TNF inhibitors'.)

Choosing between TNF versus IL-17 inhibition may be influenced by comorbid conditions. For example, IL-17 inhibitors are more effective for severe psoriasis but not for inflammatory bowel disease or iritis. In the absence of these considerations, treatment selection is based on patient, physician, and payor preference. Many clinicians reserve these agents for patients who do not have an adequate treatment response to at least one TNF inhibitor. (See 'Axial disease resistant to initial tumor necrosis factor inhibitor' below.)

Use of the TNF inhibitors for axial disease in patients with PsA is supported by evidence of benefit for axial spondyloarthritis in trials involving patients with ankylosing spondylitis [17] as well as by expert opinion [15,21,22] (see "Treatment of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'TNF inhibitors'). Available TNF inhibitors and recommendations for dosing are provided in the table (table 2).

Axial disease resistant to initial tumor necrosis factor inhibitor — In patients with axial symptoms that do not respond adequately to initial therapy with a TNF inhibitor, we switch to a second TNF inhibitor (table 2), IL-17 inhibitor (ie, secukinumab or ixekizumab), or Janus kinase (JAK) inhibitor.

Use of IL-17 inhibitors for axial disease has been supported in several clinical trials:

●Secukinumab – In the MAXIMIZE trial, secukinumab (150 or 300 mg weekly for four weeks, then monthly thereafter) was more effective than placebo for the treatment of PsA-associated axial disease at week 12 (ASAS20 64 versus 31 percent) with a safety profile that paralleled that observed in patients with PsA with peripheral joint involvement (table 3) [23]. Additionally, two ankylosing spondylitis trials (MEASURE 1 and 2) have shown a clear benefit of secukinumab compared with placebo, providing indirect evidence of benefit for this agent for the axial disease of PsA [24]. (See "Treatment of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'Secukinumab'.)

An intravenous formulation of secukinumab is also available.

●Ixekizumab – We use ixekizumab in axial PsA based on data from axial spondyloarthritis. (See "Treatment of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'Ixekizumab'.)

●JAK inhibitors – JAK inhibitors are recommended based on their efficacy for the treatment of ankylosing spondylitis. Two clinical trials for tofacitinib [25,26] and two phase 3 clinical trials for upadacitinib [27-29] have demonstrated significant improvements in magnetic resonance imaging (MRI) of the spine and sacroiliac joints compared with placebo in patients with ankylosing spondylitis.

●Ustekinumab – IL-12/23 inhibitors (eg, ustekinumab) are not currently recommended for axial disease given their lack of efficacy for the treatment of axial spondyloarthritis [30]. (See "Treatment of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'Biologic and other agents effective in other diseases but not axial SpA'.)

However, a post hoc analysis of a clinical trial suggest that it may be effective for axial spondyloarthritis [31]. A randomized clinical trial designed specifically to examine the efficacy of ustekinumab for axial PsA is underway [32].

Axial disease resistant to multiple agents — For patients who do not have an adequate response (or have a contraindication to) TNF inhibition and secukinumab, we transition the patient to ixekizumab. A case series reported clinically meaningful improvement in PsA axial disease outcomes (improvement of 1.1 or more points in Ankylosing Spondylitis Disease Activity Score [ASDAS]) in half of the patients (8 of 16) upon switching from secukinumab to ixekizumab [33]. This is consistent with our clinical experience with switching to a second IL-17 inhibitor.

For patient who do not have an adequate response (or have a contraindication to) JAK inhibition and multiple TNF and IL-17 inhibitors, an IL-23 inhibitor (ie, guselkumab) may be considered. However, the most recent Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) recommendations found that evidence was conflicting or insufficient to make a recommendation for this therapeutic class specifically in axial PsA [18,20].

●Guselkumab – In a post hoc analysis of PsA patients enrolled in two clinical trials (DISCOVER 1 and 2) who had axial involvement, patients treated with guselkumab 100 mg every eight weeks experienced improvements in spinal pain, as measured by a 10-point visual analog scale (-2.7 versus -1.2). Patients treated with guselkumab 100 mg every four weeks experienced similar improvements in spinal pain (-2.5 versus -1.2) [34]. (See "Treatment of peripheral psoriatic arthritis", section on 'Guselkumab'.)

ENTHESITIS AND DACTYLITIS — Enthesitis and dactylitis often benefit from the therapies being used to treat other clinical manifestations [35,36].

Enthesitis — In patients with enthesitis, which often affects the plantar fascia and the Achilles tendon insertion, we suggest initial treatment with nonsteroidal antiinflammatory drugs (NSAIDs) (table 1).

Local measures, including physical therapy and local glucocorticoid injection into the entheses, are sometimes beneficial, but their use has not been systematically evaluated in patients with psoriatic arthritis (PsA). We avoid glucocorticoid injection into the Achilles insertion, which has been associated with tendon rupture. Glucocorticoid injections into the plantar fascia and epicondyles are better tolerated.

In patients with functional limitation due to enthesitis, in whom NSAIDs, local measures, and treatments for other manifestations are insufficient to control the inflammation, we suggest either a biologic agent (eg, a tumor necrosis factor [TNF] inhibitor) or conventional nonbiologic disease-modifying antirheumatic drugs (DMARDs) [37].

●Most of the biologic DMARDs (TNF, interleukin 17 [IL-17], IL-12/23, IL-23 inhibitors) and Janus kinase (JAK) inhibitors used for peripheral arthritis have also been reported to be effective for enthesitis [38].

•In a head-to-head trial of upadacitinib versus adalimumab for PsA, enthesitis resolved by week 24 in over half of patients taking oral upadacitinib (either 15 or 30 mg daily), 47 percent of patients taking subcutaneous adalimumab (40 mg every other week), and 32 percent of patients taking placebo [39].

•In a study of 403 patients with enthesitis from PsA, ixekizumab (80 mg subcutaneous every four weeks) resulted in a significantly higher resolution of enthesitis than placebo (39 versus 21 percent) [40].

●Methotrexate may be effective for the treatment of enthesitis. The SEAM-PsA clinical trial compared etanercept and combination etanercept and methotrexate treatments with methotrexate alone in active PsA and found no difference in enthesitis change scores or enthesitis resolution among the treatment arms [41]. However, a placebo group was not included in this trial.

●Apremilast has also been shown to improve enthesitis and may be more effective than methotrexate for the treatment of enthesitis [42].

Dactylitis — Dactylitis generally occurs in association with disease activity in other domains (eg, peripheral joint disease). In such cases, treatments are generally selected based on these other domains, rather than the dactylitis alone.

When present in isolation, we treat mild dactylitis (ie, affecting one or two digits and not interfering with function) with NSAIDs or conventional DMARDs (eg, methotrexate 15 to 25 mg once weekly). We treat moderate to severe dactylitis (ie, affecting multiple digits or interfering with function) with biologic DMARDs or JAK inhibitors.

We treat dactylitis refractory to systemic therapies with glucocorticoid injection (eg, triamcinolone 10 mg). Ultrasound guidance may be useful for clinicians who are not experienced in the delivery of glucocorticoids into the intraarticular space of the small joints or inside the tendon sheaths that are involved by dactylitis. Flexor or extensor tendons or their insertions should never be directly injected due to risk of injury or rupture and loss of tendon function.

In a study of 44 patients with PsA presenting with dactylitis (who had not previously been treated with either methotrexate or biologic DMARDs), treatment with golimumab and methotrexate was superior to methotrexate alone when measured either with MRI or clinical assessment at 24 weeks [43].

Other studies of biologic DMARDs and JAK inhibitors have reported improvements in dactylitis as secondary outcomes [44]. However, less than half of patients in these trials had dactylitis. For example:

●In the SEAM-PsA trial, efficacy for dactylitis (measured as change in the Leeds dactylitis index at 24 weeks, as well as percentage with complete resolution of dactylitis) was similar among patients treated with subcutaneous etanercept (50 mg weekly) versus oral methotrexate (20 mg weekly) [41]. Combining methotrexate and etanercept did not improve the dactylitis response rate.

●In a head-to-head trial of upadacitinib versus adalimumab for PsA, dactylitis resolved by week 24 in over 75 percent of patients taking oral upadacitinib (either 15 or 30 mg daily), 74 percent of patients taking subcutaneous adalimumab (40 mg every other week), and 40 percent of patients taking placebo [39].

●In a study of 155 patients with dactylitis from PsA, ixekizumab (80 mg subcutaneous every four weeks) resulted in a significantly higher resolution of dactylitis than placebo (78 versus 24 percent) [40].

LIMITED ROLE OF GLUCOCORTICOIDS — Use of oral glucocorticoids in patients with psoriatic arthritis (PsA) should generally be avoided due to the risk of psoriatic flare. However, oral glucocorticoids are prescribed for rare patients with severe flares unresponsive to nonsteroidal antiinflammatory drugs (NSAIDs) and conventional or biologic disease-modifying antirheumatic drugs (DMARDs). Glucocorticoids are sometimes prescribed for other conditions, in which case there needs to be collaborative management.

We suggest tapering glucocorticoids slowly (eg, every three days); rapid reductions in glucocorticoid dose are associated with an increased risk of erythroderma or pustular psoriasis. A systematic review of studies including patients with PsA or psoriasis indicated that glucocorticoids (in the absence of taper) are associated with a low risk of flare affecting the joints [45]. In patients requiring chronic therapy with systemic glucocorticoids, the lowest dose necessary (eg, less than 5 mg daily of prednisone) should be employed.

Injection of glucocorticoids into tendon insertions should not be performed because of a risk of tendon rupture, and data supporting efficacy of this approach are not available.

Intraarticular glucocorticoids are sometimes used, and care should be taken in patients who require such injections to avoid injection through psoriatic plaques. We use intraarticular triamcinolone 40 mg for large joints and 20 mg for small joints. (See "Intraarticular and soft tissue injections: What agent(s) to inject and how frequently?", section on 'Use of glucocorticoid injections'.)

MONITORING — Patients require monitoring at regular intervals to assess the response to therapy for the psoriatic arthritis (PsA) and related morbidities and to adjust therapy based upon treatment response and adverse medication effects. Patients should be monitored more closely when new medications are being initiated, depending upon the expected response time.

We monitor patients at three-month intervals when the disease is more active or when treatments are changed. Stable patients may be monitored at six-month intervals. Depending upon the medication, laboratory monitoring may be required more often, sometimes at monthly intervals (table 4).

●Disease activity – Disease activity should be assessed by use of joint counts for detection of painful and swollen joints.

In addition, the number of areas affected by enthesitis should be assessed, with particular attention, at a minimum, to the Achilles tendon insertions and the plantar fascia in each foot, as well as the epicondyles, since these areas have been shown to be most commonly affected [46].

An identification and a count of the number of digits affected by dactylitis should be made. Dactylitis is more common in toes than in fingers and may be missed if feet are not examined.

Other measures created for use in rheumatoid arthritis, such as the RAPID3 (a modification of the Routine Assessment of Patient Index Data) and the DAS28-CRP (Disease Activity Score using a 28 joint count and C-reactive protein), may be helpful, but they only reflect peripheral arthritis. Active PsA may still be present in patients with a good response based upon these measures; thus, they cannot be used alone to determine when to stop escalation of therapy.

●Imaging and joint injury – We use plain-film radiography of clinically involved peripheral joints, sacroiliac joints, and the spine to assess the extent of disease and to track disease progression. We obtain radiographs at these sites every two years, or more frequently if there is clinical evidence of disease progression.

●Laboratory testing – Laboratory testing depends primarily upon the specific therapeutic agents being used (table 4).

Acute phase measures (eg, the sedimentation rate and CRP) should be included in the initial assessment, in part because of their prognostic implications. (See 'Risk factors for progressive joint damage' below.)

In the treat-to-target approach, treatment is adjusted at frequent and defined intervals (eg, every three months) if the target is not met (see 'Treat-to-target approach' above). The benefits of this strategy were supported by a multicenter open-label trial in the United Kingdom involving 206 patients with recent-onset active PsA who had not previously received DMARD therapy [11]. Patients who were assigned to tight control (every four week visits with prespecified treatment escalation if the target was not met) were significantly more likely to achieve American College of Rheumatology (ACR) composite criteria for at least 20 percent improvement (an ACR20 response) at 48 weeks, compared with patients receiving standard care as defined by their treating clinician (ACR20 in 44 versus 18 percent; odds ratio [OR] 1.91, 95% CI 1.03-3.55). It is important to note, however, that combination therapies prescribed in this trial for some patients, including cyclosporine and combined treatment with methotrexate and leflunomide, are not commonly prescribed in the United States for PsA. While patients were evaluated every four weeks in this study, this frequency may not be feasible or necessary in clinical practices.

ROLE OF SURGERY — We consider joint replacement surgery for patients with severe joint destruction that impacts their daily activities and is unlikely to improve with immunosuppression. We also consider surgical repair of tendons in the hands and the Achilles in patients with significant pain and dysfunction.

When a patient may have a partial tendon rupture in addition to tendonitis, ultrasound and/or MRI imaging are recommended to establish the correct diagnosis. Such patients should be referred to a plastic or orthopedic surgeon if the patient is at imminent risk of tendon rupture.

In general, surgical outcomes among psoriatic arthritis (PsA) patients are comparable to the outcomes in patients with osteoarthritis [47]. However, the long-term outcomes of joint replacement surgery in patients with PsA have not been well studied [47-49]. Total hip joint replacement and small joint arthroplasty may result in excess bone proliferation or periarticular fibrosis that impair long-term mobility [50].

The joint replacement procedures available to patients with PsA are similar to the procedures available to patients with end-stage rheumatoid arthritis. (See "Surgical management of end-stage rheumatoid arthritis", section on 'Surgical options'.)

PROGNOSIS

Clinical course — Psoriatic arthritis (PsA) was once considered a mild disease for which clinicians were reluctant to use disease-modifying antirheumatic drugs (DMARDs). However, it has since become clear that the disease is more severe than previously described [51]. Two years after disease onset in an early disease cohort, 47 percent of patients had radiographic erosions in the hands and feet, and 56 percent were taking DMARDs. In another prospective cohort study of 100 patients with PsA, the majority of patients showed progression in the number of joints involved, and 68 percent manifested radiographic progression at five years [52,53]. (See "Clinical manifestations and diagnosis of psoriatic arthritis".)

Some clinical and genetic risk factors for disease progression have been identified. Such information can help to prospectively identify patients who will benefit from aggressive early treatment. Severe disease may adversely affect survival.

Complete relief of joint tenderness and swelling may occur in a substantial minority of treated patients. As an example, in a study of 391 patients, 69 (18 percent) achieved remission, and nearly one-half remained free of active joint disease without continued use of medication [54]. Periods of remission lasted an average of approximately 2.5 years. However, the majority experienced at least one relapse after a mean duration of remission of 2.6 years.

Predictors of achieving remission include [54,55]:

●Male sex

●Mild disease

●Less disability at presentation

●Low body mass index (BMI)

●Use of biologic agents

The Madrid Sonographic Enthesis Index (MASEI) was significantly more severe in association with human leukocyte antigen B27 (HLA-B27) in the presence of longer disease duration in a PsA cohort [56]. In the same cohort, a high MASEI was associated with peripheral joint damage (higher modified Steinbrocker Score, ankyloses, arthritis mutilans, and periostitis) and axial damage (modified Stoke Ankylosing Spondylitis Spine Score and sacroiliitis) [57] after adjustment for age, sex, PsA duration, BMI, smoking, and current use of DMARDs and biologics.

Females with PsA have worse quality of life, higher disease activity, and shorter biologic drug survival than males with PsA [58,59].

Risk factors for progressive joint damage — PsA patients with the following risk factors for progressive joint damage may merit more aggressive therapy and closer follow-up:

●Increased numbers of actively inflamed joints – Polyarticular rather than oligoarticular presentation, higher tender and swollen joint counts, a high number of joint effusions, and the damage present predict progression of clinical and radiologic damage [60-64]. Of 129 patients with PsA identified in an early arthritis clinic, the number of patients with at least one erosion in the hands or feet increased from 27 percent at baseline to 47 percent by the two-year follow-up [65].

●Elevated acute phase reactants – A low erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) generally indicates that the patient is at low risk for progression [63]. In addition, each mm/hour increase in the ESR is associated with a 2 percent increased risk of progression of both clinical and radiologic damage [64].

●Failure of previous medication trials – A high level of past medication use (particularly glucocorticoids) predicts progression of clinical damage [60,61].

●Joint damage – The importance of aggressive treatment of inflammatory joint disease is supported by the finding that inflammation in a particular joint predicts progression of damage in that joint [66].

●Anti-citrullinated peptide antibodies – The presence of anti-citrullinated peptide antibodies (ACPA) is associated with an increased prevalence of polyarthritis and of erosive joint disease in a cross-sectional study of patients with PsA [67]. In one study of 588 patients with PsA, ACPA were detected in 7 percent [68]. It is not known whether these antibodies are present in early disease (and could help predict disease course) or if they develop later in the illness.

●Elevated MASEI sonographic enthesitis score – As above.

HLA typing provides important predictive information, but we do not perform such testing routinely in our practice. However, with further developments, HLA testing may have greater potential to provide clinically useful prognostic information. In univariate analysis, patients who are HLA-B27-, -B39-, or -DQw3-positive are at a higher risk for progression of clinical damage; these antigens are stronger prognostic factors than the clinical variables [69]. The presence of HLA-DR7 appears to be "protective," predicting less progression. The best multivariate model identified HLA-B27 when -DR7 is present, and -DQw3 when -DR7 is not present, as predicting disease progression. HLA-B39 was associated with progression in early disease [69]. HLA-B22 is protective when all HLA antigens are added to the model [70].

Haplotypes HLA-B27:05:02/C-02:02:02 and HLA-B08:01:01/C-07:01:01 were associated with the highest tertile of a PsA severity propensity score based on the presence of enthesitis, dactylitis, sacroiliitis, joint deformity, joint fusion, erosion, and osteolysis [71].

Cardiovascular disease and mortality

●Cardiovascular disease – Patients with PsA may be at increased risk for cardiovascular disease and/or death. In one study, patients with either psoriasis or PsA had a significant increased risk of myocardial infarction, angina, and hypertension versus the general population [72].

●Mortality – Conflicting data exist concerning the association between PsA and increased mortality [73-76]. Survival appears to have improved since the late 1970s and early 1980s, possibly related to more effective therapeutic approaches [73]. A single-center study of 453 patients with PsA in the United Kingdom between 1985 and 2007 found no increase in mortality risk compared with the general population [77]. A meta-analysis of 12 studies of PsA demonstrated a slightly increased mortality among female (relative risk [RR] 1.19) but not in male (RR 1.02) patients [78]. In this meta-analysis, PsA patients had a higher risk of mortality from cardiovascular (RR 1.21), respiratory (RR 3.37) and infectious (RR 2.43) causes but not malignancy (RR 1.01).

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Psoriatic arthritis in adults" and "Society guideline links: Spondyloarthritis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Psoriatic arthritis in adults (The Basics)")

●Beyond the Basics topic (see "Patient education: Psoriatic arthritis (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Pretreatment recommendations – Treatment of psoriatic arthritis (PsA) should be started early in disease and be coordinated among a rheumatologist, a primary care clinician, and other specialists (eg, a dermatologist). Differences in response to individual therapies between the skin and joints, and among different musculoskeletal manifestations, are commonly observed.

Treatment is guided initially by an assessment of disease severity, including the degree of disease activity, damage, and impact on the patient for each clinical domain. A treat-to-target approach should be employed, with a target of remission/inactive disease or low/minimal disease activity. Attention to the most severely and impactful involved region should guide therapy (figure 1). (See 'Pretreatment recommendations' above.)

●Management of peripheral arthritis – The management of the peripheral arthritis of PsA is discussed separately. (See "Treatment of peripheral psoriatic arthritis".)

●Management of axial disease

•Mild axial disease – In patients with mild axial disease (eg, patients with inflammatory back pain that does not interfere with function), we suggest nonsteroidal antiinflammatory drugs (NSAIDs) in antiinflammatory-dose regimens (table 1) (Grade 2B). Suggested regimens include naproxen 375 to 500 mg twice daily, indomethacin 100 to 150 mg daily in divided doses, or celecoxib 200 mg twice daily. (See 'Mild axial symptoms' above.)

•Moderate to severe axial disease – In patients with axial symptoms that do not respond adequately to treatment with NSAIDs, we recommend a tumor necrosis factor (TNF) or interleukin 17 (IL-17) inhibitor (Grade 1B). Nonbiologic disease-modifying antirheumatic drugs (DMARDs) appear to be ineffective in axial spondylitis, and therefore are not used for axial disease in PsA.

The choice of agent and dosing are the same as those used for peripheral arthritis, except that IL-12/23 inhibitors (eg, ustekinumab) are not recommended due to lack of consistent evidence for benefit in axial spondyloarthritis (table 2). (See 'Moderate to severe axial disease' above.)

•Axial disease unresponsive to initial tumor necrosis factor inhibitor – In patients with axial symptoms that do not respond adequately to initial therapy with a TNF inhibitor, we switch to a second TNF inhibitor or an alternative agent such as secukinumab, ixekizumab, or a Janus kinase (JAK)/signal transducer and activator of transcription (STAT) inhibitor. Other options may include guselkumab and ustekinumab. (See 'Axial disease resistant to initial tumor necrosis factor inhibitor' above.)

•Axial disease unresponsive to multiple agents – In patients with axial symptoms that do not respond adequately to therapy with TNF inhibition or secukinumab, we switch to ixekizumab.

For patients who do not respond adequately to therapy with several agents, including JAK inhibition and multiple TNF and IL-17 inhibitors, we would consider guselkumab, although the data supporting the use of this drug for axial PsA are poor. (See 'Axial disease resistant to multiple agents' above.)

●Management of enthesitis – In patients with enthesitis, a response is often seen with medications used for other manifestations of PsA.

In patients with enthesitis causing functional impairment who do not respond to NSAIDs and local therapy, we suggest using a biologic agent, initially a TNF inhibitor (table 2) (Grade 2C). (See 'Enthesitis' above.)

●Management of dactylitis – In patients with dactylitis who do not respond to NSAIDs, we treat with a conventional DMARD (eg, methotrexate 15 to 25 mg once weekly), and if that is inadequate, we use a biologic agent (Grade 2C). Treatment with a biologic agent is likely to be necessary in patients with severe dactylitis that affects multiple digits. (See 'Dactylitis' above.)

●Limited role for glucocorticoids – Use of oral glucocorticoids in patients with PsA should be avoided, and when required (eg, for severe flares), the dose should be the minimum needed. It is important to taper the glucocorticoids with close observation for the development of erythroderma or pustular psoriasis.

Intraarticular glucocorticoids are sometimes used, and care should be taken in patients who require such injections to avoid injection through psoriatic plaques. (See 'Limited role of glucocorticoids' above.)

●Disease monitoring – Clinical monitoring of disease should include joint counts that assess both the upper and lower extremities as well as the number of areas involved by enthesitis and by dactylitis.

Plain film radiography of clinically involved peripheral joints, the sacroiliac joints, and the spine are also used to assess the extent and progression of disease at these sites.

Laboratory and clinical monitoring is also advised for certain medication regimens (table 4). (See 'Monitoring' above.)

●Surgery – Joint replacement surgery may be necessary for patients with severe joint destruction. However, long-term outcomes of joint replacement surgery in patients with PsA have not been well described (See 'Role of surgery' above.)

●Prognosis – PsA has variable disease expression; a significant proportion of patients may develop destructive and potentially disabling disease. Factors predicting a poor prognosis include a higher number of actively inflamed joints, an elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), failure of previous medication trials, the presence of joint damage, loss of function, and diminished quality of life. (See 'Prognosis' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Christopher Ritchlin, MD, MPH, who contributed to earlier versions of this topic review.