Biologic efficacy for complications associated with moderate-to-severe psoriasis

Different manifestations of psoriasis

Psoriasis is a multi-faceted disease, with patients often experiencing more than one psoriasis associated complication at some point in their lifetime. These manifestations include the typical skin-affecting disease, the most common of which is plaque psoriasis (80–90% of cases) (Figure 1). Other skin-affecting manifestations include inverse psoriasis, erythrodermic psoriasis, guttate psoriasis and pustular psoriasis. 

​

Figure 1: Commonly affected areas for the different manifestations of psoriasis; skin-affecting disease, psoriatic arthritis (enthesitis, nail enthesitis, dactylitis, nail psoriasis) and nail psoriasis.​

Non-skin complications associated with psoriasis include psoriatic arthritis and nail psoriasis. Psoriatic arthritis affects 20–30% of psoriasis patients. It is a chronic inflammatory disease that can affect multiple joints including peripheral joints (peripheral disease), sacroiliac joints and the spine (axial disease). In 20% of affected patients, psoriatic arthritis is severe and leads to debilitating and progressive damage to the joints, particularly when left untreated. Besides the typical features, psoriatic arthritis patients may experience inflammatory musculoskeletal lesions such as enthesitis and dactylitis. Enthesitis is present in 60–80% of psoriatic arthritis patients and affects the attachments of tendons and ligaments or nails at distal interphalangeal (DIP) joints. Dactylitis is characterised by uniform swelling and inflammation of digits of the feet and hands and occurs in 16–49% of patients who have psoriatic arthritis1. Early treatment of psoriatic arthritis can limit the amount of damage caused by both enthesitis and dactylitis. 
Nail psoriasis is another visible manifestation of psoriasis and is associated with higher prevalence of psoriatic arthritis. Nail psoriasis mostly affects the fingernails and can involve nail crumbling, ridging, splitting, discolouration and separation. 

Treatment for psoriasis complications- is there a two-in-one hit solution? 

One of the key unmet needs in psoriasis is selecting the right treatment for a patient based on their individual disease features. Indeed, there are limited treatment options for patients who present with multiple manifestations of psoriasis. Treatment selection should also be based on other patient circumstances not associated directly with psoriasis. For instance, not all treatments are suitable for women who are likely to have children, who are pregnant or who are breastfeeding.

For more on suitable treatments for young women, please visit Part 2 of this series.   

Many of the clinical manifestations of psoriasis, including psoriatic arthritis and nail psoriasis, appear to share mechanisms of onset related to the deregulation of the inflammation pathways associated with skin-based disease. Subsequently, some biologic agents that target the inflammation pathways have proven to be efficacious in more than one setting, with indications for more than one psoriasis manifestation, and indeed, other chronic inflammatory diseases (Figure 2). This is particularly true for the biologic treatments which have been approved earlier on. 

​

​Figure 2: EMA approved biologic treatments for moderate-to-severe psoriasis and psoriatic arthritis

In Europe, the TNF-α inhibitors (etanercept, infliximab, adalimumab and certolizumab pegol) are all indicated for both moderate-to-severe plaque psoriasis and psoriatic arthritis. Other biologic treatments with both indications include the IL-12/IL-23 inhibitor ustekinumab and the IL-17 inhibitors secukinumab and ixekizumab (Figure 2). All of these biologic treatments show vast improvements in both PASI and ACR20 scores when compared to placebo alone. However, very few clinical trials have directly compared one biologic to another. It is therefore not possible to conclude which biologic is best in efficacy for either moderate-to-severe psoriasis or psoriatic arthritis. Whilst the limited existing data provide an indication on superiority, many of these studies require further validation.

Are the biologic treatments approved for both moderate-to-severe psoriasis and psoriatic arthritis also suitable for patients with enthesitis, dactylitis and nail psoriasis? 

Psoriatic arthritis may be further complemented by enthesitis, dactylitis and nail psoriasis. The RAPID-PsA study on certolizumab pegol highlights vast improvements in the total resolution of dactylitis (93.3%), enthesitis (87.5%) and nail psoriasis (67.7%) at week 2164. Ustekinumab (PSUMMIT II), secukinumab (FUTURE I) and ixekizumab (UNCOVER-3, SPIRIT-P1 and SPIRIT-P2) also demonstrated improvements in all three manifestations. Similarly, infliximab also significantly improved enthesitis and dactylitis (IMPACT II) and nail psoriasis (EXPRESS).
The data on etanercept and adalimumab is currently less clear and requires further validation. Etanercept significantly improved nail psoriasis in one study, whilst another uncontrolled study (no placebo, PRESTA) showed improvements in both enthesitis and dactylitis. For adalimumab, early data (ADEPT) indicated that there was no significant improvement in enthesitis, dactylitis or nail psoriasis, whereas the BELIEVE study found improvements in nail psoriasis. 
Based on these findings, not all of the seven biologics that are indicated for both moderate-to-severe psoriasis and psoriatic arthritis are suitable for patients who suffer with additional manifestations of psoriatic arthritis. 

How should we treat psoriasis patients who have failed prior biologic treatment?

Some patients experience biologic treatment response failure that may be due to lack of initial efficacy, loss of efficacy over time or development of adverse events. For moderate-to-severe psoriasis, overall data indicates that switching biologic treatments for patients who experience response failure is a reasonable option. The outcomes range from partial to near expected response in patients who failed on one previous biologic to partial response in patients who failed on multiple biologic treatments. This is also true when switching from one TNF- α inhibitor to another since the biologic structures vary enough despite targeting the same factor. For instance, etanercept given to patients who don’t respond to infliximab and adalimumab also provides partial improvements in both PASI and PGA scores. Infliximab also showed some efficacy in patients who failed on etanercept.   

For psoriatic arthritis, certolizumab pegol and secukinumab are recommended for patients who have stopped responding to a previous TNF- α inhibitor after the first 12 weeks. For certolizumab pegol, the phase 3 randomised RAPID-PsA study indicated that psoriatic arthritis response was maintained over four years, in patients both with and without prior TNF-a inhibitor exposure5. This study also indicated maintained improvements in psoriasis, nail disease, enthesitis and dactylitis over the four-year study, with little radiographic progression in structural joint damage.

Concluding remarks

The discussion from this three-part series focussed on the use of biologic treatments for women of childbearing age, in patients with multiple psoriasis-related disease features, and variable biologic responses. The discussion highlights that health care providers need to give very careful consideration to the individual patient circumstance and psoriasis disease features when planning treatment.

Further reading 

Part 1 : Moderate-to-severe psoriasis: the disease burden and unmet needs in different patient groups
Part 2 : Moderate-to-severe psoriasis: treatment for young women