Janssen wish to announce that the European Commission has approved the use of Stelara (ustekinumab), alone or in combination with methotrexate, for the treatment of active psoriatic arthritis in adult patients when the response to previous non-biological disease-modifying anti-rheumatic drug (DMARD) therapy has been inadequate.1
Stelara, a human anti-interleukin (IL)-12 and IL-23 monoclonal antibody, is currently approved for the treatment of moderate to severe plaque psoriasis.1It is estimated that up to 30 percent of people living with psoriasis may develop psoriatic arthritis2, a chronic autoimmune disease characterised by joint swelling and tenderness, periarticular tissue inflammation including enthesitis (inflammation of the site where ligaments or tendons insert into the bones) and dactylitis (inflammation of an entire digit), as well as psoriasis.3
The European Commission provided approval based on a review of data from two pivotal Phase III multicentre, randomised, double-blind, placebo-controlled trials of ustekinumab in patients with active psoriatic arthritis (PSUMMIT I and PSUMMIT II).4,5 Stelara is the first in a new class of biologics now available for patients living with active psoriatic arthritis.
PSUMMIT I and II design
ustekinumab 45mg or 90mg at weeks 0, 4 and then every 12 weeks compared to placebo. The trials included patients diagnosed with active psoriatic arthritis who had at least five tender and five swollen joints and C-reactive protein levels of at least 0.3mg/dL despite previous treatment with conventional DMARD.
PSUMMIT II also included patients who had previously experienced treatment with TNF inhibitors.5
The primary endpoints for both studies were the proportion of patients demonstrating at least a 20% improvement in arthritis signs and symptoms (American College of Rheumatology [ACR] 20) at week 24.<sup>4,5</sup> The studies also captured improvements in the soft tissue components of psoriatic arthritis, including enthesitis and dactylitis scores for patients with enthesitis and/or dactylitis at baseline. For psoriatic arthritis patients with skin involvement, improvements in skin symptoms were assessed with the Psoriasis Area and Severity Index (PASI) responses, and the proportions of patients achieving at least a 75% improvement in the index (PASI 75) were measured.4,5
More patients more achieved ACR20 with Stelara
n both trials, treatment with ustekinumab resulted in significant improvements in the measures of disease activity at week 24, as significantly more ustekinumab-treated patients achieved ACR20 compared to placebo.4,5
In PSUMMIT I, the proportion of patients achieving ACR20 at week 24 was 42% in the ustekinumab 45mg group and 50% in the ustekinumab 90mg group versus 23% in the placebo group (p<0.0001 for both comparisons), and responses were maintained at week 52.4 In PSUMMIT II, the proportions of patients achieving ACR20 at week 24 were 44%, 44% and 20% in the ustekinumab 45mg and 90mg groups versus the placebo group, respectively (p<0.001 for both comparisons).5
Responses observed in the ustekinumab treated groups were similar in patients receiving and not receiving concomitant MTX.4 Patients previously treated with anti-TNFα agents who received ustekinumab achieved a greater response at week 24 than patients receiving placebo (ACR 20 response for 45mg and 90mg was 37% and 35%, respectively, compared to 15% with placebo; p<0.02).5
Improvements in enthesitis and dactylitis scores
For patients with enthesitis and/or dactylitis at baseline, results of PSUMMIT I demonstrated significant improvements in enthesitis scores (43% and 50% median improvements; p=0.0019 and p<0.0001, respectively) as well as in dactylitis scores (75% and 71% median improvements; p=0.0003) at week 24 in the ustekinumab 45mg and 90mg groups, respectively, compared to placebo (see Figures 1 and 2).4
At week 52 the median improvements in enthesitis were found to be 74% and 88% in the ustekinumab 45mg and 90mg groups, respectively, while a 100% improvement in dactylis was observed in all groups (see Figures 1 and 2).4
Maintained improvement of skin symptoms
In addition, ustekinumab provided sustained improvement of skin symptoms, with significantly more psoriatic arthritis patients with skin involvement (patients where BSA ≥3%) achieving at least a PASI 75 at week 24 in the ustekinumab groups (p<0.0001 for all group comparisons to placebo) (PSUMMIT I, see Figure 3).4
At week 52, 68% and 70% of patients achieved PASI 75 in the ustekinumab 45mg and 90mg groups, respectively (see Figure 3).4,6
Figure 1: PSUMMIT 1 – Median percent change from baseline in enthesitis at Week 24 and Week 52*4,6
† p=0.0019; ‡ p<0.0001 (click on figure to enlarge)
Figure 2: PSUMMIT 1 – Median percent change from baseline in dactylitis at Week 24 and Week 52*4,6
† p=0.0003 (click on figure to enlarge)
Figure 3: PSUMMIT 1 – PASI 75 response in patients with skin involvement (BSA ≥3%)*4,6
† p<0.0001; PASI 75: at least a 75% improvement in the psoriasis area and severity index. (click on figure to enlarge)
* For patients who qualified for early escape, data or prior to week 16 were carried through week 24. Data are for the intention to treat population from baseline to week 24; after week 24, observed data were used.
Conclusion
“The European Commission approval of Stelara for the treatment of active psoriatic arthritis brings an important new therapeutic option to patients and marks the first treatment approved for this devastating and complex disease since the introduction of anti-tumour necrosis factor (TNF)-alpha agents,” said Jerome A. Boscia, M.D., Vice President, Head of Immunology Development, Janssen Research & Development.
He added: “Data from the Phase III clinical program, one of the largest conducted for a biologic to date in psoriatic arthritis, showed Stelara effective in improving symptoms and signs of active psoriatic arthritis in anti-TNF-alpha naïve and experienced patients. We believe Stelara will play a critically important role in the treatment of this chronic disease moving forward.”
References:
1- Stelara Summary of Product Characteristics September 2013. Available from www.medicines.ie.
2- About Psoriatic Arthritis. National Psoriasis Foundation. http://www.psoriasis.org/psoriatic-arthritis. Accessed October 17 2013.
3- Diagnosing Psoriatic Arthritis. Available from http://psoriasis.org/psoriatic-arthritis/diagnosis. Accessed November 2013.
4- McInnes IB et al. Lancet. 2013 Aug 31;382 (9894):780-9.
5- Ritchlin CT et al. Presented at ACR, Washington DC, USA 9th-14th November 2012.
6- Kavanaugh et al. Poster presented at ACR/AHRP annual meeting. 2012, November 12-14; Washington DC. Poster P4.
Full prescribing information and references available from Janssen. Telephone: (01) 6202300. MIMS Ireland Copyright®