TNF inhibitors
Adalimumab is a human monoclonal antibody with a high affinity for TNFα. Adalimumab is licensed for use in adults with severe psoriasis and PsA in whom conventional therapies have failed or are not tolerated.
Evidence of its efficacy in treating both psoriasis and PsA is available from numerous RCTs. Different outcome measures were improved in the treatment arms, such as Psoriasis Area and Severity Index (PASI75) [
4], American College of Rheumatology (ACR) responses and PsA Response Criteria (PsARC), together with Health Assessment Questionnaires (HAQ), Health Assessment Questionnaire Disability Index (HAQ-DI), Short form-36 health survey (SF-36
), Dermatology Life Quality Index (DLQI) score, Mental Component Summary Score (MCSS) and Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale [
5‐
8]. Radiographic progression as measured by the modified total Sharp score at weeks 24 and 48 was lower in those treated with adalimumab irrespective of whether they were receiving methotrexate (MTX) at baseline [
5,
8].
Adalimumab has also demonstrated its superiority when compared to conventional therapies, such as methotrexate and cyclosporine [
9,
10]. In addition, combination of DMARDs and adalimumab also showed superiority to monotherapy [
10].
Adalimumab has been compared directly and indirectly with other drugs in the TNF inhibitor group (infliximab, etanercept, adalimumab and golimumab) in patients with PsA [
11‐
13]. All treatments have demonstrated similar outcomes and safety profiles. There is also evidence of additional benefit when switching from one anti-TNF drug to another [
14,
15].
The clinicians’ choice for a biologic therapy in a particular patient may be guided by the drug ability to tackle specific manifestations of these diseases, such as axial disease, dactylitis, enthesitis and nail disease. Adalimumab is effective for the treatment of dactylitis and enthesitis [
16]. One RCT [
17] and three observational studies have shown effectiveness of adalimumab in nail disease as assessed by Nail Psoriasis Severity Index (NAPSI) [
18‐
20]. A recent publication by the medical board of the National Psoriasis Foundation has recommended the use of adalimumab in patients with nail disease alone, skin and nail disease or for patients with a combination of nail, skin and joint disease [
21]. Adalimumab was ranked with the “highest enthusiasm” compared to all other drugs recommended for nail psoriasis.
Adalimumab showed improvement of axial disease in patients with ankylosing spondylitis (AS), regardless of concomitant presence of psoriasis [
22]. In summary, adalimumab has shown clear benefits in joint and skin disease. Studies have shown a clear reduction in disability and improved quality of life. Adalimumab may also be the drug of choice for patients with dactylitis, enthesitis and nail disease. It may also be of use in patients in whom MTX is ineffective, or other TNF inhibitors have failed, or in combination with cyclosporine [
23].
Etanercept is a fusion protein consisting of the p75 receptor bound to the Fc region of human immunoglobulin (Ig) G1. It has shown efficacy at 12 weeks for PsARC, ACR20, ACR50 and ACR70, PASI75 response criteria and improvement in the quality of life, patient rating of pruritus and patient global assessment of psoriasis and physician global assessment (PGA) [
24‐
31]. It was also shown to inhibit radiographic progression at 12 and 24 months [
32,
33]. A meta-analysis assessing etanercept efficacy in comparison with other TNF inhibitors has found a lower relative risk (RR) for a PASI75 response at week 12, as well as a lower RR for PASI75 at 24 weeks than for adalimumab, golimumab and infliximab [
3].
An observational study looking at patients with PsA with axial disease found that 72 % of patients had an improved Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score whilst taking etanercept [
34].
Etanercept is an effective treatment for enthesitis and dactylitis, with improvements documented at week 12 and week 24 in a multiple-dose study [
35]. Similar efficacy has also been demonstrated in psoriatic nail treatment [
36,
37]. Etanercept is currently recommended by the medical board of the National Psoriasis Foundation for use in isolated nail disease, skin and nail disease, and nail and skin and joint disease [
21].
In summary, etanercept has proven efficacy in skin and joint disease as well as nail disease, dactylitis and enthesitis, and may relieve symptoms of fatigue and depression, although, as detailed above, it appears as it is less effective than other anti-TNF drugs.
Infliximab is a chimeric monoclonal antibody against TNFα, with demonstrated efficacy for treating psoriasis [
38‐
41]. In parallel, the drug has also been proven effective in PsA. The IMPACT RCT demonstrated significant ACR20 response at week 16 [
39], and additional improvement in quality of life as assessed by HAQ score and SF-36 health survey at week 14 [
42] and week 16 [
39]. The efficacy in improving PASI75, PASI90, ACR20, ACR50 and ACR70 responses was sustained at week 54, regardless of baseline methotrexate use [
43]. Infliximab significantly inhibited progression of radiographic damage at week 24 [
44].
The EXPRESS RCT found significant improvement in nail disease for % improvement in NAPSI score and nail matrix and bed features at weeks 10 and 24 (26.8 and 57.2 %, respectively, in the infliximab group versus −7.7 and −4.1 %, respectively, in the placebo group, both
p < 0.001). The IMPACT RCT found significant improvement in dactylitis and enthesitis scores at week 16 [
39], and these were maintained until week 54 in the IMPACT-2 RCT [
43].
Infliximab has demonstrated superiority compared to conventional treatments, as assessed by both PsA and psoriatic outcome measures [
45,
46].
Infliximab has also demonstrated efficacy in psoriasis for patients with an inadequate response to etanercept: in the PSUNRISE RCT, at week 10, 65.4 % of patients had achieved a PGA score of 0 or 1 (indicating clear or almost clear disease), and this was sustained until week 26: 61.3 % [
47].
Certolizumab is a PEGylated Fab’ fragment of a humanised TNF inhibitor monoclonal antibody, which has been proven beneficial in treating psoriasis [
48] and PsA. Certolizumab has also been associated with preserved efficacy in patients with previous exposure to TNF inhibitors [
49], sustained effectiveness [
50], and additional benefit in improving the quality of life [
51] and productivity [
52]. In addition, there was significant inhibition of radiographic progression as measured by the modified total Sharp score at week 24 [
53].
Certolizumab is also effective in treating enthesitis, dactylitis and nail disease associated with PsA and psoriasis, showing a significant difference versus placebo regardless of the dose [
49].
Golimumab is a novel monoclonal antibody against TNFα, engineered in a transgenic mice model. The GO-REVEAL RCT demonstrated significant efficacy for treating psoriasis and PsA at week 14 as measured by ACR20 and PASI75 responses, and positive impact on quality of life, as reflected by significant improvements in the HAQ [
54]. Efficacy was maintained at 5 years [
55]; however, 31 % of patients had discontinued treatment after 5 years. Golimumab also proved to be effective in treating enthesitis at week 24 [
54,
56]; however, dactylitis score was only significantly decreased with the 100-mg dose of golimumab compared to placebo [
56]. Golimumab was also effective in treating nail disease [
54].