Table 4.

Recommendations

1. Goals of therapy 1. Treatment should be aimed at reaching the target of remission or, alternatively, minimal/low disease activity, by regular monitoring and appropriate adjustment of therapy. In PsA, there exist few data regarding natural history, treatment objectives and remission. However, since in PsA inflammation is related to long-term outcomes of joint involvement, this recommendation states that the objective in patients with PsA is remission or if remission cannot be achieved, a low or minimal disease activity state. Remission is defined here as the absence of clinical and laboratory evidence of significant inflammatory disease activity. In addition to absence of inflammation in the joints, absence of enthesitis and dactylitis are also important. It should be noted that this remission of inflammation may not equate to complete absence of all symptoms for many patients. Indeed, recent work in PsA demonstrated that the impact of the disease on quality of life is related to pain, skin problems and functional disability, and fatigue, as well as emotional and social aspects of impact. Some of these aspects of impact may be less accessible to pharmacological therapies of PsA, thus leading to a ‘residual’ impact in the absence of inflammation. Furthermore, remission may be difficult to achieve in PsA. Factors associated with higher remission rates appear to be younger age, lower functional impairment and higher C reactive protein levels in some cases. Remission is still insufficiently defined in PsA. We suggest that the use of outcomes where remission/low disease activity have been defined, should be considered. This is now the case for several scores used in PsA, some of which focus only on arthritis whereas others encompass various aspects of psoriatic disease. As regards joint involvement, a stringent remission definition and criteria for low disease activity by the Disease Activity index for Psoriatic Arthritis (DAPSA) have been recently defined and validated. However, minimal/low disease may also be a relevant target especially for long-standing disease, as stringent remission may not be achievable in these patients or in some patients with comorbidities that preclude escalation of therapy. Minimal disease activity in PsA has been defined as five of the seven criteria comprising musculoskeletal and skin manifestations and patient-reported outcomes. This outcome has been shown in one study to be predictive of less structural degradation, and in the recent Tight control in PsA (TICOPA) trial to be a valid treatment target. Definitions of remission and acceptable residual disease activity levels in PsA, its predictors and its relationship with long-term outcomes are still a part of the research agenda and more thorough assessment of prognostic markers of severity (related to risk of progressive disease, structural damage, physical disability and quality of life) must still be addressed. (EULAR recommendation 1)

2. Screening and management of TB, HIV, HB/CV, Chagas’ disease, leishmaniasis, leprosy, and other concomitant comorbidities GRAPPA treatment of PsA and concomitant comorbidities. See Table 5. Since the SLR did not find evidence to make recommendations, expert opinion is provided. Given the endemic nature of TB, HIV, HBV/HCV, Chagas’ disease, leishmaniasis, leprosy, and other infectious diseases, it is recommended that appropriate screening for prevalent infections be conducted as per local and national guidelines prior to initiation of immunosuppressive therapies (especially bDMARDs). Periodically thereafter and ideally at each clinical encounter careful assessment for active infection should be conducted to avoid serious, life threatening infectious complications.

3. Frequency of monitoring Since the SLR did not find evidence to make recommendations, expert opinion is provided. Patients need to be evaluated periodically to assess response to therapy and identify complications and adverse events. The frequency of monitoring should depend on the time to expected response when starting a new csDMARD/bDMARD and the degree of disease activity. Less frequent follow up may be acceptable when disease is well controlled, and changes in therapy are not anticipated.

4. Safety and efficacy of pharmacotherapy in all domains GRAPPA treatment schema, recommendations for each domain. See Fig. 3. Since the SLR did not find evidence to make recommendations about safety of bDMARDs in TB endemic areas, expert opinion is provided. We recommend that the GRAPPA recommendations on treatment be followed although we recognize that access to many therapies, especially bDMARDs may be difficult in resource poor settings. Appropriate screening for endemic disease such as tuberculosis (such as chest X-ray and Mantoux or IGRAs) prior to therapy and periodic evaluation during therapy with bDMARDs, especially TNFi agents as per local guidelines are recommended.

5. Efficacy and safety of combination therapy Recent data suggest that continuation of a concomitant csDMARD therapy in combination with TNFis is beneficial in PsA in terms of treatment maintenance and levels of response, especially in patients using monoclonal antibodies, but more data are warranted including the effect of concomitant csDMARD on immunogenicity. (EULAR recommendation 5) Since the SLR did not find evidence to make recommendations, expert opinion is provided. The efficacy and safety of combination of biologic therapy with csDMARDs as well as combination with tsDMARD therapy is not well established. Such therapy may be used carefully with frequent monitoring of response and adverse events, especially organ toxicity and infections.

6. Safety and efficacy of biosimilars and intended copies Since the SLR did not find evidence to make recommendations, expert opinion is provided. Use of biosimilars may be considered in the management of psoriatic arthritis with careful monitoring of adverse events, especially infections, as recommended when using bDMARDs. We do not recommend the use of intended copies, until proper evaluation of their efficacy and safety.

bDMARDs biological DMARD, csDMARDs conventional synthetic DMARDs, such as methotrexate, sulfasalazine, or leflunomide; DMARDs disease-modifying anti-rheumatic drugs, tsDMARDs targeted synthetic DMARDs, HIV human immunodeficiency virus, HB/CV hepatitis B/C virus, PsA psoriatic arthritis, SLR systematic literature review, TB tuberculosis, TNFi tumor necrosis factor inhibitors, GRAPPA Group for Research and Assessment of Psoriasis and Psoriatic Arthritis, EULAR European League Against Rheumatism