Efficacy and safety of secukinumab in Chinese patients with psoriatic arthritis: Evidence from a real-world study

Psoriatic arthritis (PsA) is a chronic, systemic inflammatory disease that affects peripheral and axial joints, entheses, skin, and nails. It seriously reduces the quality of life and psychosocial function. Although tumor necrosis factor inhibitors (TNFi) significantly improve patient outcomes in PsA, there is still a significant unmet need. Secukinumab was first approved in China for moderate-to-severe plaque psoriasis in 2019, and has shown significant efficacy.[1] However, studies assessing secukinumab in Chinese PsA patients are scarce.[2] Therefore, we evaluate the efficacy and safety of secukinumab in Chinese PsA patients in a real-world setting. The patients were recruited from the Peking University First Hospital Psoriatic Arthritis (PKUPsA) cohort, a longitudinal observational cohort.[3] By January 2023, there were 453 PsA patients in the cohort and we included all the patients who received secukinumab therapy in this study. The study was approved by the Ethical Committee of Peking University First Hospital (2019-267), and informed consent was obtained from each patient. Demographic and laboratory parameters were collected. At each follow-up, disease activity index for psoriatic arthritis (DAPSA) scores, psoriasis area and severity index (PASI), nail psoriasis severity index (NAPSI), and patient-reported outcomes (PROs) were assessed. Musculoskeletal ultrasound examination included bilateral wrists, ankles, and other affected joints, and entheses of the Leeds Enthesitis Index.[4] Categorical variables were presented as proportion and percentage. Normally distributed continuous variables were presented as mean ± standard deviation, and those deviating from normal distribution as median (Q1, Q3).We analysed the disease activity parametres and PROs with Generalized Estimated Equation. Pearson’s χ2-test, Yates’ correction for continuity, or Fisher’s exact test was used to compare categorical variables. Response rates were compared based on Kaplan–Meier survival curves using the log-rank test. P <0.05 was considered statistically significant. Data analysis was performed with SPSS 26.0 (IBM Corp., Armonk, NY, USA). A total of 56 subjects were included and analyzed, with a mean age of 46.2 ± 14.1 years and 41 (73.2%) males. Twenty-three (41.1%) patients reported a family history of psoriasis or PsA. Skin lesions occurred first in 48 (85.7%) patients. The median duration of skin lesions and arthritis were 14.0 (10.3, 22.0) years and 4.0 (1.0, 10.8) years, respectively. Regarding smoking, there were 57.4% (31/54) current smokers or smoking-ever patients, 11.1% (6/54) secondhand smokers, and 31.5% (17/54) never smokers. There were 48.1% (26/54) patients with overweight (30.0 kg/m2>body mass index [BMI] ≥25.0 kg/m2) and 16.7% (9/54) with obesity (BMI ≥30.0 kg/m2). There were 35.7% (20/56) patients with hyperuricemia, including 1 with gout. Two (3.6%) patients had cardiovascular diseases [Supplementary Table 1, https://links.lww.com/CM9/C158]. From the aspect of musculoskeletal involvement, 10.7% (6/56) patients manifested as the monoarthritic type, 44.6% (25/56) as oligoarticular type, 41.1% (23/56) as polyarticular type, and 19.6% (11/56) as axial involvement. Dactylitis was detected in 34.5% (19/55) patients, and clinical and/or subclinical acute enthesitis was found in 49.1% (27/55) patients. On ultrasound, tendinitis/tenosynovitis was identified in 65.5% (36/55) patients, and synovitis in 54.5% (30/55) patients. Totally, 67.9% (38/56) patients had nail disease and 5.4% (3/56) patients had a history of iridocyclitis, but none had inflammatory bowel disease. At baseline, most patients had low-to-moderate disease activity, with a median DAPSA score of 9.8 (6.2, 14.8) [Table 1]. There were 91.1% (51/56) with current skin lesions, and 54.2% (26/48) with health assessment questionnaire (HAQ) score of above zero. Totally, 41 patients completed various questionnaires of PROs. Based on the generalized anxiety disorder-7 (GAD-7) scale, mild, moderate, and severe anxiety were reported in 12, 1, and 2 patients, respectively. Based on the patient health questionnaire-9 (PHQ-9) assessment, mild, moderate, and severe depression were reported in 8, 3, and 1 patients, respectively. Totally, 95.1% (39/41) patients reported varying degrees of fatigue, with a median functional assessment of chronic illness therapy-fatigue (FACIT-F) score of 9 (7, 13), and median self-assessment self-reported health state (SRHS) score was 70 (63, 80). Table 1 - Changes of disease activity index, PASI, NAPSI, and patient-reported outcomes during 12 months. Items Baseline 1 month 3 months 6 months 12 months P trend values TJC 2 (1, 3) 1 (0, 2) 1 (0, 2) 0 (0, 1) 0 (0, 1) <0.001 SJC 1 (1, 2) 1 (0, 2) 1 (0, 2) 0 (0, 1) 0 (0, 1) 0.006 ESR (mm/h) 15 (7, 25) 9 (5, 15) 8 (5, 13) 8 (5, 13) 9 (6, 17) 0.144 CRP (mg/L) 5.5 (2.3, 14.0) 3.0 (1.7, 5.0) 2.1 (1.4, 5.7) 2.0 (1.1, 3.6) 2.6 (1.1, 6.5) 0.409 VAS 23 (10, 40) 15 (10, 24) 10 (5, 20) 10 (3, 15) 5 (0, 10) <0.001 PGA 30 (16, 40) 13 (10, 24) 10 (8, 20) 10 (5, 20) 5 (0, 10) <0.001 EGA 23 (10, 30) 10 (10, 20) 10 (5, 20) 10 (5, 14) 5 (0, 10) <0.001 DAPSA 9.8 (6.2, 14.8) 5.0 (2.8, 9.3) 4.3 (3.1, 6.4) 3.2 (1.4, 5.9) 2.3 (0.7, 5.1) <0.001 PASI 4.0 (0.7, 8.7) 2.0 (0.5, 8.7) 0.3 (0, 1.9) 0.1 (0, 1.2) 0.1 (0, 1.2) <0.001 NAPSI 6.6 (0, 22.8) 1.0 (0, 21.5) 1.0 (0, 18.3) 0 (0, 13.0) 1.5 (0, 3.8) 0.009 HAQ 1 (0, 4) 0 (0, 3) 0 (0, 1) 0 (0, 0) 0 (0, 1) 0.069 GAD-7 3 (0, 7) 2 (0, 6) 0 (0, 2) 0 (0, 2) 0 (0, 1) 0.001 PHQ-9 2 (0, 6) 2 (1, 6) 0 (0, 2) 0 (0, 3) 0 (0, 2) 0.002 FACIT-F 9 (7, 13) 8 (3, 11) 8 (5, 11) 8 (3, 9) 8 (3, 9) 0.762 SRHS 70 (63, 80) 80 (70, 85) 83 (80, 90) 90 (80, 90) 90 (81, 94) 0.002 PsAQoL 0 (0, 4) 0 (0, 3) 0 (0, 1) 0 (0, 3) 0 (0, 1) 0.018 Data are presented as median (Q1, Q3). CRP: C-reactive protein; DASPA: Disease activity index for psoriatic arthritis; EGA: Evaluator global assessment; ESR: Erythrocyte sedimentation rate; FACIT-F: Functional assessment of chronic illness therapy-fatigue; GAD-7: Generalized anxiety disorder-7; HAQ: Health assessment questionnaire; NAPSI: Nail psoriasis severity index; PASI: Psoriasis area and severity index; PGA: Patient global assessment; PHQ-9: Patient health questionnaire-9; PsAQoL: Psoriatic arthritis quality of life scores; SJC: Swelling joint count; SRHS: Self-reported health state; TJC: Tenderness joint count; VAS: Visual analog scale. Before exposure to secukinumab, nine patients were naïve to biological/conventional/targeted synthetic disease-modifying antirheumatic drugs (b/cs/tsDMARD). Secukinumab was administered in two different dosages, 300 mg in 39 patients and 150 mg in 17 patients. Secukinumab was prescribed as monotherapy in 13 patients, and combined with other DMARDs in 43 patients, mainly methotrexate (34 patients) [Supplementary Table 1, https://links.lww.com/CM9/C158]. The median duration of secukinumab treatment was 12.0 (7.5, 16.0) months. Most PsA patients were gradually improved after secukinumab treatment. Cumulative American College of Rheumatology 20, 50 and 70 (ACR 20, 50, and 70) response rates were 87.1%, 79.2%, and 33.7% at 6 months, respectively, and 89.2%, 84.4%, and 59.9% at 12 months, respectively. Among 47 patients who were not in minimal disease activity (MDA) at baseline, cumulative MDA-achieving rates were 68.1% and 76.6% at 6 months and 12 months, respectively. There were eight patients with DASPA remission at baseline. At 6 months and 12 months, cumulative DASPA remission was achieved in 58.3% (28/48) and 60.4% (29/48) patients, respectively [Supplementary Figure 1, https://links.lww.com/CM9/C158]. The disease activity index showed a downward trend with extented treatment duration, especially in the first month. DAPSA score dropped from 9.8 (6.2, 14.8) at baseline to 2.3 (0.7, 5.1) at 12 months (Ptrend <0.001). Moreover, most patients achieved DAPSA-defined remission or showed low disease activity. Meanwhile, skin and nail lesions were also greatly improved, as well as PROs, including anxiety and depression [Table 1]. PsA patients with dactylitis were more likely to achieve ACR 20/50 than those without (ACR 20: 100% vs. 83.2%, P <0.001; ACR 50: 94.7% vs. 76.5%, P = 0.014), but less likely to achieve DASPA-defined remission (56.9% vs. 84.7%, P = 0.026). The ACR 50 response rate was lower in patients with nail disease than those without (77.9% vs. 94.1%, P = 0.031), but the rates of DASPA-defined remission and MDA achievement were similar. No significant differences were observed in effective indexes in patients with other domains compared with those without. We also analyzed the efficacy of secukinumab in patients with different PsA domains based on ultrasound findings. The results revealed that patients with tendinitis/tenosynovitis and/or synovitis were more likely to achieve ACR 20 (97.1% vs. 72.2%, P = 0.004; 92.9% vs. 85.0%, P = 0.033). However, patients with acute enthesitis (56.5% vs. 92.7%, P = 0.009), tendinitis/tenosynovitis (63.6% vs. 94.1%, P = 0.001), and synovitis (56.4% vs. 91.1%, P = 0.008) hardly achieved DASPA-defined remission. In addition, patients with synovitis (82.6% vs. 100%, P = 0.012) and tendinitis (85.4% vs. 95.3%, P = 0.036) had lower MDA achievement rate. At baseline, some PROs were worse in the 300 mg group compared with the 150 mg group (HAQ 2 [0, 5] vs. 0 [0, 1], P = 0.026; GAD-7: 3 [0, 7] vs. 0 [0, 5], P = 0.060; PHQ-9: 4 [1, 8] vs. 1 [0, 3], P = 0.035; FACIT: 11 [8, 15] vs. 7 [2, 9], P = 0.006; SRHS: 70 [60, 80] vs. 80 [70, 88], P = 0.049). Moreover, disease activity indexes were higher in the 300 mg group than 150 mg group although the differences were statistically insignificant (DASPA: 10.2 [6.4, 16.3] vs. 8.2 [3.8, 12.4], P = 0.273; PASI: 4.4 [1.0, 7.9] vs. 3.2 [0.4, 12.8], P = 0.660). ACR 20/50/70 response and MDA achievement rates of both groups were similar at 12 months; however, higher response rates were observed in the 300 mg group compared to 150 mg group (ACR 20: 94.4% vs. 76.5%; ACR 50: 88.4% vs. 71.4%; ACR 70: 63.6% vs. 53.0%; MDA achievement rate: 94.4% vs. 73.0%; P <0.05 for all). During the study period, seven (12.5%) patients reported adverse events, including upper respiratory tract infection (three patients), urinary tract infection (two patients), oral candidiasis (one patient), and leukopenia (one patient); however, no serious adverse event was found. There was no trend of worsening or recurrence in three patients with a previous malignancy (rectal cancer, ladder carcinoma, or cutaneous melanoma) and in one patient with bipolar disorder. Latent tuberculosis (TB) and/or hepatitis B virus (HBV) infection were presented in 18 (32.1%) patients before using secukinumab. Four patients received prophylactic anti-TB treatment and only patient with positive HBV surface antigen was prescribed for prophylaxis. There was no TB or HBV relapse event in the entire follow-up. In summary, the real-world study of secukinumab in Chinese PsA patients showed superior efficacy and good tolerability. Secukinumab could improve skin lesions and arthritis symptoms, the functional status, and the quality of life. Conflicts of interest None.