Skyrizi vs Tremfya (Risankizumab Vs Guselkumab) is a comparison of the two monoclonal antibodies which selectively target and block Interleukin-23.
IL-23 is an inflammatory cytokine that activates CD4 + T-helper (Th17) cell pathway to activate the inflammation cascade that is responsible for psoriatic plaque formation. Both of these drugs are indicated in the treatment of plaque psoriasis in adults who are eligible for systemic therapy or phototherapy.
Mechanism of action (MOA) of Skyrizi vs Tremfya (Risankizumab Vs Guselkumab):
Skyrizi (Risankizumab) MOA:
Risankizumab acts to inhibit the release of cytokines and chemokines that are responsible for inflammatory skin conditions. It binds with high affinity to the p19 subunit of IL-23 and inhibits its attachment to IL-23 receptor.
This in turn stops the type-1 T cell-mediated inflammatory response. Type 1 T-cells are in high concentrations in skin affected with psoriasis. These cells increase the expression of inflammatory genes causing abnormal immune responses.
Tremfya (Guselkumab) MOA:
Guselkumab mainly targets the p19 subunit of IL-23. Normal inflammatory and immune responses are mediated by IL-23 while the subunits 19 and 40 are over-expressed in conditions like psoriasis and other autoimmune skin disorders.
Guselkumab binds to the p19 subunit in keratinocytes and dendritic cells and inhibits its attachment to IL-23 receptor. In this way, it blocks the abnormal signaling of inflammatory cytokines that cause epidermal abnormalities such as psoriatic plaque formation.
Pharmacokinetics of Skyrizi vs Tremfya (Risankizumab Vs Guselkumab):
|Half-life||28 days||15-18 days|
|Absorption||Achieves maximum concentration in 3-14 days||Achieves maximum concentration in 5.5 days|
Skyrizi vs Tremfya (Risankizumab Vs Guselkumab): Efficacy in the treatment of plaque psoriasis
- Skyrizi has been approved by FDA for the treatment of adults with moderate to severe psoriasis. The recommended dosage for psoriasis is 150 mg as two subcutaneous injections of 75mg, at weeks 0, 4, and then after every 12 weeks.
- The efficacy of Risankizumab was evaluated in the pivotal phase III trial. In the short-term treatment, Risankizumab was significantly more efficacious than adalimumab and Ustekinumab. A greater proportion of patients being treated with Risankizumab achieved skin clearance.[Ref]
- Risankizumab also improved health-related quality of life as assessed by the Dermatology life quality index and psoriasis symptom scale. It has also been found effective for the long-term treatment of moderate to severe plaque psoriasis. In various clinical trials, Risankizumab therapy is found to be more effective than Adalimumab, Ustekinumab, and Secukinumab for the treatment of psoriasis.[Ref]
- Tremfya (Guselkumab) selectively targets IL-23 and is approved to treat psoriasis. Various clinical trials have proved the efficacy of Guselkumab in the long-term treatment of psoriasis. The recommended dosage of Tremfya for psoriasis is 100 mg at week 0, 4, and then every 8 weeks.
- In one study large, randomized, phase III trials were conducted to assess the clinical efficacy of subcutaneous Guselkumab in the treatment of psoriasis, the results suggested that Guselkumab is more efficacious than adalimumab in reducing disease symptoms and improving the overall quality of life. It was statistically superior to adalimumab for treating regional psoriasis.[Ref]
Read: TNF Inhibitors; An Overview of Their Use in Immune-mediated Diseases
Safety and Tolerability of Skyrizi vs Tremfya (Risankizumab Vs Guselkumab):
- Risankizumab is generally well-tolerated in patients with plaque psoriasis. In a 16- week pooled analysis of patients receiving Risankizumab, Ustekinumab and adalimumab the results suggest that the most common side effect was upper respiratory tract infection. The most common serious adverse events were cellulitis and squamous cell carcinoma (0.2%).
- Risankizumab showed the lowest percentage of common as well as serious side effects among all the above-mentioned drugs. It was well tolerated through 2.5 years of continuous treatment. Injection site reactions were also low (4%) in patients receiving Risankizumab therapy.[Ref]
- Risankizumab has the potential for immunogenicity. Anti-drug antibodies and neutralizing antibodies were detected in patients. Although in most cases it did not have any effect on the efficacy of the drug.[Ref]
- In all the clinical trials Guselkumab was generally well tolerated. Nasopharyngitis and upper respiratory tract infections were common adverse events. In one clinical trial, two major adverse cardiac events occurred in patients receiving Guselkumab therapy and another patient developed basal cell carcinoma.
- In the same trial, between weeks 16 and 48 four more cases of serious infections were reported and two more malignancies (breast and prostate cancer) were also observed. Serious AEs were 7% in patients receiving Guselkumab and 2% discontinued treatment due to adverse events.[Ref]
- The incidence of antibodies is 6% with Guselkumab therapy however, it includes non-neutralizing antibodies. There is no association between antibody incidence and low efficacy.
Skyrizi vs Tremfya (Risankizumab Vs Guselkumab): Use during pregnancy and lactation
Both Skyrizi and Tremfya are monoclonal antibodies. The action of most of these antibodies is similar to that of maternal antibodies, however, their permeability through the placenta is not identical. Biological drugs have a limited ability to cross the placenta during 1st trimester, but they can cross the barrier during 2nd and 3rd trimesters.
Different structures of these drugs cause different permeability. The binding affinity of the Fc receptor is highest for complete monoclonal antibodies and is low for etanercept and absent for certolizumab pegol. For this reason, other drugs (Adalimumab, Infliximab, Ustekinumab, Secukinumab, Guselkumab, and Risankizumab) are not recommended to be used during pregnancy or lactation.
Pregnancy in psoriasis patient increase risk of maternal disease and therapy use on fetal development, but drug discontinuation can also affect mother’s health and disease severity. Although some women experience improvement in symptoms, in some cases disease condition deteriorates. In these conditions, IL-23 Inhibitors must be used in exceptional circumstances only.[Ref]
Although both drugs are almost equally efficacious in the treatment of psoriasis. Risankizumab is a better treatment option than Guselkumab due to its low incidence of severe side effects and infections.
A study conducted on the comparative efficacy of biologics in the treatment of psoriasis showed that Risankizumab was superior in efficacy and overall safety as compared to Guselkumab.[Ref]
Read: Biologics for Psoriasis (TNF, IL-23, IL-39, IL-17, and CD-6 Inhibitors)