Eli Lilly and Company has announced that psoriatic arthritis (PsA) patients treated with ixekizumab for 24 weeks achieved significant improvements in signs and symptoms of their disease when compared to placebo, while also experiencing significantly less progression of radiographic structural joint damage, reduced disability when performing certain physical functions and improved skin clearance of plaque psoriasis.
In announcement issued on Monday, Lilly said that detailed results of the SPIRIT-P1 study were presented during the American College of Rheumatology/Association of Rheumatology Health Professionals (ACR/ARHP) Annual Meeting in San Francisco. Ixekizumab is the company’s investigational medicine for the treatment of active PsA and moderate-to-severe plaque psoriasis.
“The SPIRIT-P1 data show that ixekizumab may be able to address unmet or underserved needs that many patients living with psoriatic arthritis have, including the reduction of painful and debilitating skin and joint inflammation, which are the hallmarks of this chronic disease,” said Philip Mease, M.D., chief of rheumatology research, Swedish Medical Center, and clinical professor, University of Washington, Seattle. Dr. Mease is a SPIRIT-P1 study investigator.
During the 24-week, double-blind period of this Phase 3 study, patients who had never received a biologic disease-modifying antirheumatic drug (bDMARD) were treated with either 80 mg of ixekizumab once every two weeks or every four weeks (following a 160 mg starting dose); adalimumab at the approved dose of 40 mg every other week; or placebo. Adalimumab was employed as an active control in the SPIRIT-P1 study and was not powered for comparison with ixekizumab treatment groups.
Significant Improvements in Disease Signs and Symptoms, Structural Joint Damage
In both dosing regimens, ixekizumab-treated patients demonstrated significant improvements compared with placebo in disease activity of PsA as demonstrated by the proportion of patients achieving an ACR20 response at 24 weeks, the study’s primary objective. Improvements were experienced by ixekizumab-treated patients as early as one week after treatment initiation. ACR20 represents at least a 20 percent reduction in a composite measure of disease activity as defined by the ACR. Other measures included ACR50 and ACR70, which represent 50 percent and 70 percent reductions in disease activity, explained the company.
Furthermore, at 24 weeks, 62 percent of patients treated every two weeks and 58 percent of patients treated every four weeks with ixekizumab achieved ACR20 compared with 30 percent of placebo-treated patients. The proportions of ixekizumab-treated patients who achieved ACR50 when treated every two weeks or every four weeks were 47 percent and 40 percent, respectively, compared with 15 percent of patients treated with placebo. Furthermore, 34 percent of patients treated with ixekizumab every two weeks and 23 percent of those treated every four weeks experienced a 70 percent reduction in disease activity. Six percent of patients treated with placebo achieved this level of improvement.
Patients treated with ixekizumab at both dosing regimens also experienced significantly less radiographic progression of structural joint damage than those treated with placebo, as measured by the change from baseline in the van der Heijde modified total Sharp score (mTSS) for PsA at 24 weeks. Structural joint damage caused by PsA may lead to permanent joint deformity and reduced physical function.
Reduced Disability in Physical Function, Improved Skin Clearance
Lilly says that Ixekizumab treatment groups also experienced significant improvements compared with placebo in other key secondary measures, including physical function as assessed using the Health Assessment Questionnaire Disability Index (HAQ-DI), and improved skin clearance of plaque psoriasis as measured by the Psoriasis Area and Severity Index (PASI), including PASI75, 90 and 100. A PASI75 score indicates at least a 75 percent reduction in a patient’s plaque psoriasis from the patient’s baseline assessment, while PASI90 reflects a 90 percent reduction and PASI100 represents a 100 percent reduction, reflecting complete skin clearance.
Efficacy results with adalimumab compared with placebo during the SPIRIT-P1 study were significant on most measures. At 24 weeks, 57 percent of patients treated with adalimumab, the study’s active control, achieved ACR20, while 39 percent and 26 percent achieved ACR50 and ACR70, respectively.
The incidence of treatment-emergent adverse events (TEAE) was greater with ixekizumab treatment compared with placebo. The most common (≥4 percent) adverse events observed with ixekizumab treatment were injection site reaction, injection site erythema and nasopharyngitis. These events are consistent with those reported in the Phase 3 studies of ixekizumab for the treatment of moderate-to-severe plaque psoriasis (UNCOVER 1, 2, 3). Serious adverse events and discontinuation rates due to adverse events were not significantly different between treatment groups.
“Many people living with this debilitating disease are still searching for an effective treatment,” said J. Anthony Ware, M.D., senior vice president, product development, Lilly Bio-Medicines.
“These results further support our continuing investigation of ixekizumab for the treatment of psoriatic arthritis, and our belief that this investigational medicine may offer a viable choice in the future for people seeking a better way to manage their disease.”