Study Population

In total, 337 patients were enrolled into SUSTAIN between February 2015 and March 2017, for a planned observation period of 160 weeks. There were 146 (43.3%) patient discontinuations before week 160, which includes 104 (30.9%) patients who discontinued treatment owing to a lack or loss of efficacy or worsening of PsA/psoriasis, and 13 (3.9%) patients who withdrew because of AEs. Overall, 129 (38.3%) patients treated with ustekinumab were documented at week 160; of these, 125 (37.1%) patients were still receiving treatment at this timepoint (i.e., 4 patients discontinued treatment at the week 160 visit).

Baseline Characteristics

Baseline disease characteristics of the 129 patients documented at week 160 are summarized in Table 1 (for baseline demographics, see Supplementary Table 1). At baseline, 94 (72.9%) and 61 (47.3%) patients had peripheral small and large joints that were affected by PsA, respectively, and 14 (10.9%) patients had axial involvement. In addition, 25 (19.4%) patients had active dactylitis, 19 (14.7%) had enthesitis, and 4 (3.1%) had uveitis.

Table 1 Baseline disease characteristics of the analysis populationBaseline Concomitant Diseases and Prior Therapies for PsA

Overall, 109/129 (84.5%) patients had a concomitant disease at baseline, the most common being vascular disorders (n = 75, 58.1%), metabolism and nutrition disorders (n = 59, 45.7%), and musculoskeletal and connective tissue disorders (n = 52, 40.3%) (Table 2).

Table 2 Concomitant diseasesa at baseline in the analysis population (prevalence > 5%)

Before enrollment, 123/129 (95.3%) patients had received prior therapies for PsA (Table 3). The most common were MTX (n = 102, 79.1%) and ibuprofen (n = 41, 31.8%). In total, 56 (43.4%) patients had received one or more TNF inhibitor, including adalimumab (n = 39, 30.2%), etanercept (n = 32, 24.8%), golimumab (n = 18, 14.0%), certolizumab (n = 6, 4.7%) and infliximab (n = 4, 3.1%).

Table 3 Prior therapies for PsA in the analysis population

Patients received prior PsA therapies for a mean of 6.8 (standard deviation [SD] 7.6) years. The reasons for discontinuation of prior therapies are presented in Supplementary Table 2; of note, a lack of tolerability led to discontinuation of MTX for 41 (50.6%) patients, while lack of efficacy was the main reason for discontinuation of biologic therapies.

Ustekinumab Exposure

The 45 mg dose was given to 89 (69.5%) patients, while the 90 mg dose was given to 39 (30.5%) patients; data were missing for 1 patient. The mean weight-adjusted ustekinumab dose was 0.7 (SD 0.2) mg/kg body weight. Concurrent MTX was taken by 69 (53.5%) patients, while an alternative DMARD was taken by 9 (7.0%) patients.

Joint Counts

Mean decreases from baseline to week 4 were observed for both TJC (8.0 to 5.8; Fig. 1a) and SJC (4.5 to 3.1; Fig. 1a); these decreases continued up to around week 28 and were sustained over the remainder of ustekinumab treatment documentation (reaching 1.0 and 0.4 for TJC and SJC at week 160, respectively). Improvements were also observed in both small peripheral and large joints as early as week 4 (Figs. 1c–f). This rapid and sustained improvement in TJC and SJC was also demonstrated in patients with axial involvement or with dactylitis (Supplementary Fig. 1).

Fig. 1

Tender and swollen joint count in the analysis population. Overall mean (a) tender and (b) swollen joint count (95% CI), split by small peripheral (c) tender and (d) swollen joint count, and large (e) tender and (f) swollen joint count. BL baseline, CI confidence interval, W week

Mean TJC and SJC decreased from baseline throughout the study irrespective of MTX use. The mean absolute decrease in TJC was similar in MTX-treated patients and those who did not receive MTX (Supplementary Fig. 2a). However, patients who did not receive MTX had a consistently greater mean reduction in SJC than MTX-treated patients (Supplementary Fig. 2b).

Skin Parameters

Both PASI and BSA affected by psoriasis decreased from baseline after 4 weeks of ustekinumab treatment (mean absolute change of −3.2% and −2.6%, respectively) and continued to decrease up to week 28 (−6.4% and −11.4%, respectively) (Fig. 2a, b). These improvements were maintained up to week 160, where the mean absolute change from baseline was –7.2% for PASI and –13.6% for BSA affected.

Fig. 2

Mean absolute change from baseline in (a) PASI and (b) BSA affected to week 160. Data show the 95% CI. BSA body surface area, CI confidence interval, PASI Psoriasis Area and Severity Index

Patient-Reported Outcomes

In line with the pattern of response observed with joint counts and skin parameters, a decrease from baseline in patient-assessed pain score was demonstrated by week 4 (mean absolute change of −10.0), with further improvements to week 28 (mean absolute change of −19.1). These improvements were maintained to week 160 of ustekinumab treatment (mean absolute change of −19.8) (Fig. 3). Similar improvements in patient-assessed sleep quality and HAQ-DI scores were also observed (Supplementary Fig. 3).

Fig. 3

Mean absolute change from baseline in pain score in patients documented at week 160. Data show the 95% CI. CI confidence interval, W week

Minimal Disease Activity Assessments

MDA was assessed at weeks 28 and 52 in patients who did not have MDA at baseline (n = 113/129). Following ustekinumab treatment, MDA was achieved by 36 (31.9%) patients at week 28, and by 38 (33.6%) patients at week 52 (Table 4). The rate of patients achieving each individual MDA criterion is also presented in Table 4. Overall, 67.1% of patients had SJC ≤ 1 and 62.1% of patients attained PASI ≤ 1 or BSA ≤ 3% at week 28; the equivalent proportions at week 52 were 69.9% and 81.0%, respectively.

Table 4 Rate of patients achieving minimal disease activity

The rate of patients achieving each individual MDA criterion in relation to overall MDA status (whether achieved or not achieved) is summarized in Supplementary Table 3. In patients without MDA, SJC ≤ 1 and PASI ≤ 1 or BSA ≤ 3% were still achieved by 62.7% and 67.2% of patients, respectively, at week 28, and 71.4% and 77.8% of patients, respectively, at week 52. For patients who successfully achieved MDA at least once during the study, the median time until MDA achievement was 42 weeks [95% confidence interval (CI) 30.0–65.9], with a median duration of 33 weeks (95% CI 23.9–71.7). Worst-case analysis resulted in a median MDA duration of 12 weeks (95% CI 0.1–26.1).

MDA achievement at weeks 28 (32.2% versus 31.5%, respectively) and 52 (30.5% versus 37.0%, respectively) was similar in patients who received concomitant MTX treatment and those who did not (Supplementary Table 4).

Ustekinumab Effectiveness Following Prior Biologic Therapies

Ustekinumab, as assessed by mean change from baseline to week 160 in TJC, SJC, enthesitis, BSA, and PASI, and MASES was effective irrespective of the number of prior biologic therapies received (Fig. 4).

Fig. 4

Mean absolute change from baseline in (a) TJC, (b) SJC, (c) PASI, (d) BSA, and (e) enthesitis, from baseline to week 160. Data show the 95% CI. Patient numbers are as follows: no biologic, n = 72; one biologic, n = 27; two biologics, n = 16; more than two biologics, n = 14. BSA body surface area, CI confidence interval, MASES Maastricht Ankylosing Spondylitis Enthesitis Score, PASI Psoriasis Activity and Severity Index, SJC swollen joint count, TJC tender joint count

Safety

Ustekinumab treatment-related AEs and SAEs were reported in 61 (47.3%) patients and 4 (3.1%) patients, respectively (Table 5), and AEs occurring in ≥ 3% of patients are presented in Table 6. Off-label use of ustekinumab (28 [21.7%] patients), which includes the use of ustekinumab at a higher dose than recommended by the summary of product characteristics, contributed to the overall number of treatment-related AEs. At week 160, 100% of patients who provided a response (n = 117) assessed the tolerability of ustekinumab as good or very good.

Table 5 Adverse events and serious adverse events during the studyTable 6 Nonserious adverse events and serious adverse events during the study