SAN DIEGO — A pooled analysis of the PSUMMIT I and PSUMMIT II trials extends the efficacy of ustekinumab beyond reducing disease activity in the joints and skin of patients with psoriatic arthritis to inhibiting joint damage.
"The pooled analysis met the prespecified major radiographic end point showing the efficacy of the interleukin 12/23 antibody in inhibiting progression of structural damage in patients with active psoriatic arthritis. Some of these patients were very sick at baseline," said lead investigator Iain McInnes, PhD, from the University of Glasgow, in the United Kingdom.
"These findings are significant since impeding further joint damage is one of the goals of long-term management of this chronic inflammatory disease," he pointed out.
Dr. McInnes presented the results here at the American College of Rheumatology 2013 Annual Meeting.
PSUMMIT I showed a slowing of radiographic progression of psoriatic arthritis with ustekinumab. The investigators used an imputation methodology for patients who dropped out of PSUMMIT II, which led to a more conservative estimate of the drug's benefit, he explained.
For the 2 studies, the design was identical, but the patient populations were different.
PSUMMIT I evaluated 615 adults with psoriatic arthritis who were naïve to biologic therapy. PSUMMIT II evaluated 312 adults with psoriatic arthritis who had active disease despite previous treatment with TNF-alpha inhibitors and disease-modifying antirheumatics or nonsteroidal anti-inflammatory drugs.
In both trials, patients were randomized to ustekinumab 45 mg, ustekinumab 90 mg, or placebo. About 50% of patients were receiving methotrexate. Positive results from these trials led to the drug's approval for psoriatic arthritis in the United States.
Dr. McInnes presented pooled data on the rate of radiographic change over the first 24 weeks of treatment for 927 patients with active psoriatic arthritis despite treatment.
At week 16, patients with no response to placebo crossed over to ustekinumab 45 mg, and patients with no response to ustekinumab 45 mg crossed over to ustekinumab 90 mg. At week 24, the remaining patients in the placebo group crossed over to ustekinumab 45 mg.
At baseline, radiographic assessments were comparable in the 3 groups.
At week 24, patients in the ustekinumab groups had significantly less radiographic progression than those in the placebo group, according to van der Heijde-Sharp (vdH-S) score. Mean change from baseline in total score was lower with ustekinumab 45 mg than with placebo, as was mean change with ustekinumab 90 mg.
Table. Change From Baseline in vdH-S Score at Week 24
| Score | Placebo Group | Ustekinumab Groups | P Value |
| Total modified | 0.97 | 0.40 | <.001 |
| Erosion | 0.57 | 0.21 | <.001 |
| Joint-space narrowing | 0.40 | 0.19 | <.001 |
The benefit of ustekinumab persisted at week 52, when mean change from baseline in vdH-S score was 0.58 for ustekinumab 45 mg and 0.65 for ustekinumab 90 mg. For placebo patients who crossed over to ustekinumab at week 16 or week 24, mean change from baseline in vdH-S score was 1.15 at week 52.
The inhibition of damage was consistent in PSUMMIT I and the pooled analysis at week 24 for ustekinumab and placebo, Dr. McInnes reported. However, in PSUMMIT II, the effect of ustekinumab on radiographic progression could not be demonstrated, probably because it was a smaller trial and radiographs were missing for 23% of patients in the placebo group.
In the 4 sensitivity analyses performed, the primary outcome of the pooled analysis did not change.
No new safety concerns were raised in the pooled safety analysis.
Even though the investigators used a more stringent imputational analysis for missing radiographic data, "they still found a beneficial effect of ustekinumab," said Eric Matteson, MD, from the Mayo Clinic in Rochester, Minnesota.
"The study showed that ustekinumab has the potential to slow radiographic erosions in patients with psoriatic arthritis," he said.
Dr. Matteson noted that it is important to know the magnitude of benefit of the drug, and which patients benefited. "The investigators have those data and they should be forthcoming," he noted.
Dr. McInnes reports financial relationships with Novartis, Janssen, and UCB Pharma. Dr. Matteson reports financial relationships with Ardea Biosciences, Celgene, Genentech, Biogen Idec, Inx, Hoffman La-Roche, Janssen, Mesoblast, Novartis, Pfizer, the Rheumatology Research Foundation, and UCB Pharma.
ACR 2013 Annual Meeting: Abstract 1695. Presented October 28, 2013.
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Cite this: Ustekinumab Stops Joint Damage in Psoriatic Arthritis - Medscape - Nov 06, 2013.
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