Abstract
Secukinumab is a novel anti-IL17 biologic treatment approved for the treatment of psoriatic arthritis (PsA). The purpose of the present study is to identify factors that can condition the retention rate of this drug in a real-world scenario. Methods: A multicentric retrospective study was conducted based on the registries of consecutive patients diagnosed with PsA who started secukinumab from January 2016 to December 2018. For purposes of Cox-regression analysis, the time spanning from the first administration of secukinumab until its interruption or the end of the follow-up was considered the independent variable. Variables of known relevance and those who demonstrated direct association with the drug retention rate were included in the model. Results: One hundred seventy-six registries were analyzed (average age at diagnosis 44.7 ± 12.1 years old, 114 females). The median retention rate of secukinumab was 636 days (95% confidence interval [CI] 542.4–729.5). Presence of peripheral arthritis (hazard ratio 0.424 [95% CI 0.213–0.847, P = .015]) and a time of evolution >6 years (hazard ratio 0.468 [95% CI 0.225–0.975, P = .043]) were the 2 variables that showed a significant influence on the drug retention rate. According to our results, patients who exhibit peripheral arthritis and those with a higher evolution time will have more probabilities of a larger secukinumab retention rate.
Keywords: psoriatic arthritis, retention rate, secukinumab
Key Points
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1.
This paper provides real-life evidence on the persistence of secukinumab in patients with psoriatic arthritis in a multicenter cohort of 4 hospitals in Madrid
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2.
Peripheral arthritis has been identified as a conditioning factor for longer drug survival in patients with psoriatic arthritis.
1. Introduction
Psoriatic arthritis (PsA) is a chronic inflammatory disease associated with psoriasis, which is included in the heterogeneous group of spondyloarthritis. The estimated overall prevalence of PsA varies from country to country, being one of the highest in Spain (0.58%) and ranging from 0.02 to 0.67%, globally.[1,2]
In recent years, progress has been in the pathogenesis of the disease, which has led to the development of new drugs that facilitate the control of PsA and Psoriasis. We currently have 13 drugs that are indicated in this disease: classical disease-modifying drugs (DMARDs) such as methotrexate and leflunomide, biological anti-TNF DMARDs, biological anti-IL17 or anti-IL12/23 DMARDs, and targeted synthetic DMARDs such as apremilast, tofacitinib, and upadacitinib.[3,4] The most relevant national and international guidelines advise the use of biologic or targeted DMARDs after failure of classic DMARDs in moderate or severe PsA.[5–7] In recent years, the relevance of the anti-IL23/IL17 therapy in the pathogenesis of PsA has become evident.[8–12] Secukinumab is an anti-IL-17 monoclonal antibody indicated for treating PsA in patients with previous inadequate response to classic DMARDs.[13] Despite the efficacy and safety data obtained in multiple clinical trials, the real-world data is still needed to support these findings.
In this clinical heterogeneity scenario, with a wide availability of therapeutic offerings, clinicians need to demand better results in terms of efficiency and safety beyond the information available predominantly from clinical trials. It is, therefore, necessary to generate information from routine clinical practice. Based on this information, comparisons can be made between therapeutic measures in terms of efficacy and safety, both surrogated to a more relevant and complex variable: drug persistence. This variable is undervalued in situations where the availability of therapeutic alternatives is limited, a circumstance that does not apply to the current state of treatment of PsA.[14,15]
The present study aims to determine the median retention rate of secukinumab in patients with PsA under routine clinical practice conditions and identify the determinants of prolonged drug retention rate.
2. Methods
A multicentric observational retrospective longitudinal study was conducted at 4 tertiary hospitals of Madrid. The centers involved in this study were Ramón y Cajal University Hospital, 12 de Octubre University Hospital, Puerta de Hierro University Hospital, and Principe de Asturias University Hospital. The period of the retrospective follow-up was from January 2016 to December 2018.
Records of patients diagnosed with PsA according to CASPAR criteria that were treated with secukinumab at any dose were included.
The time spanning from the first administration of secukinumab until its interruption was considered as the main dependent variable. To calculate the time of exposure to the drug, the start and end dates of its administration were used. These dates were checked from 3 different sources prior to their inclusion in the database: explicit record of the clinical history, pharmacy dispensing record, and follow-up and nursing care record. Independent variables collected from clinical records included sex, age at diagnosis, time since disease onset, smoking, peripheral arthritis, dactylitis or enthesitis, acute sacroiliac involvement, secukinumab dose, and the number of previous biologic or synthetic therapies (line of treatment). C-reactive protein (CRP) plasma levels, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, and visual analogic scale (VAS) of axial pain level were also registered at the start of treatment with secukinumab.
Peripheric arthritis, dactylitis or enthesitis, and acute sacroiliac involvement were considered as present or absent according to the information available from clinical records prior to the start of secukinumab. Acute sacroiliac involvement was registered using a radiological interpretation of sacroiliac magnetic resonance imaging, including osteitis or bone edema. Smoking was considered a categorical variable with 3 possible inputs: never, ex-smoker and active-smoker. An ex-smoker was defined as a person who stopped smoking at least one year ago. Previous synthetic treatments and biologic therapies included TNF-inhibitors, ustekinumab, and apremilast. Finally, we reviewed the match between the clinical, radiological, and lab features of all patients and the inclusion/exclusion criteria of both pivotal clinical assays performed previously to secukinumab market launch (FUTURE 1(8,13) and FUTURE 2(9)), see Table S1, Supplemental Digital Content 1, http://links.lww.com/MD/H254, which summarizes the inclusion and exclusion criteria).
2.1. Statistical analysis
Clinical, epidemiological and demographic variables were collected from electronic records. A bivariate analysis of categorical and numerical variables was performed. Patients were grouped according to the condition of still been on secukinumab treatment or not. A Cox regression time-to-event analysis was performed. “Event” was defined as stopping secukinumab or switching to a different therapy. Besides the variables considered plausibly related to the main dependent variable, those that reached a P < .10 value of statistical significance were also included into model. Kaplan–Meier curves were also used to determine which variables could be associated to higher retention rates of treatment. The event date was defined as the last known date the treatment was administered. All patients who remained in therapy with secukinumab after December 31th 2018, were considered as censored data.
In order to perform the Cox regression analysis, normalization of the dependent variable was performed after testing it with Kolmogorov-Smirnov’s test.
2.2. Ethical aspects
This study was approved by the Príncipe de Asturias University Hospital scientific research ethics committee, the Spanish Agency of Medicines and Medical Products, and the local ethics committees of the rest of the hospitals involved.
3. Results
One hundred seventy-six consecutive patients’ registries were included. No patient was treated with secukinumab twice; thus, each registry belonged to a single patient. Sixty-two patients were male (35.2%). Twenty-three patients were positive for the allele HLA-B*27 (13.1%). One hundred seventeen patients presented no sacroiliac radiological involvement (66.5%); however, acute lesions were identified via magnetic resonance imaging in 21 (11.9%). Peripheral arthritis was present in 151 patients (85.8%), erosions in 62 (35.2%), dactylitis in 61 (34.7%) and enthesitis in 111 (63.1%). The dose of secukinumab administered to patients at the start of each of the treatments was 150mg/month in 123 cases (69.9%) and 300 mg/month in 53 cases (30.1%). Twenty-nine patients (16.5%) met the inclusion/exclusion criteria for both pivotal clinical assays of secukinumab, 56 (31.8%) did not. In 91 patients, there was insufficient data to determine if they met both sets of criteria. The complete list of basal features of the cohort is shown in Table 1.
Table 1.
Demographic, epidemiological and clinical features of patients included.
| Feature | N (proportion) | Mean ± SD |
|---|---|---|
| Demographics | ||
| Sex | ||
| Male | 62 (35.2%) | |
| Female | 114 (64.8%) | |
| Age at diagnosis of PsA (yr) | 44.7 ± 12.1 | |
| Time since diagnosis until the start of secukinumab (yr) | 9.03 ± 6.81 | |
| Tabaquism | ||
| Never | 91 (51.7%) | |
| Ex-smoker | 37 (21%) | |
| Smoker | 48 (27.3%) | |
| BMI | 28.4 ± 6.05 | |
| Clinical and lab background | ||
| Hypertension | 55 (31.3%) | |
| Diabetes | 22 (12.5%) | |
| Hypercholesterolemia | 57 (32.4%) | |
| Ischemic heart disease | 6 (3.4%) | |
| HLA-B*27 | ||
| Positive | 23 (13.1%) | |
| Negative | 72 (40.9%) | |
| Unknown | 81 (46.0%) | |
| Clinical manifestations | ||
| Peripheral arthropathy | 151 (85.8%) | |
| Dactylitis | 61 (34.7%) | |
| Enthesitis | 111 (63.1%) | |
| Uveitis | 3 (1.7%) | |
| Psoriasis | 147 (83.5%) | |
| Inflammatory bowel disease | 2 (1.1%) | |
| Hip arthropathy | 18 (10.2%) | |
| Hip prosthesis | 11 (6.3%) | |
| Number of tender joints* | 6.9 ± 8.2 | |
| Number of swollen joints* | 3.5 ± 4.6 | |
| Axial pain level (0–10 visual analogic scale)† | 7.1 ± 1.7 | |
| Global physician assessment (0–10 visual analogic scale) | 6.5 ± 1.9 | |
| CRP determination (mg/L) | 10.7 ± 35.2 | |
| BASDAI | 4.89 ± 2.84 | |
| BASFI | 4.86 ± 2.97 | |
| Radiological features | ||
| Sacroiliitis radiological grade | ||
| None | 117 (66.5%) | |
| 1 | 19 (10.8%) | |
| 2 | 25 (14.2%) | |
| 3 | 11 (6.3%) | |
| 4 | 4 (2.3%) | |
| Sacroiliitis active lesions in MRI | 21 (11.9%) | |
| Sacroiliitis non-active morphological lesions in MRI | 30 (17%) | |
| Sindesmophites | 23 (13.1%) | |
| Erosive disease in hands and feet | 62 (35.2%) | |
| Treatments | ||
| Treatments previous to start secukinumab | ||
| Prednisone | 83 (47.2%) | |
| NSAIDs | 167 (94.9%) | |
| Methotrexate | 135 (76.7%) | |
| Salazopyrine | 86 (48.9%) | |
| Leflunomide | 66 (37.5%) | |
| Number of previous biologic treatments or targeted DMARDs | ||
| None | 58 (33%) | |
| 1 | 39 (22.2%) | |
| 2 | 30 (17%) | |
| 3 | 23 (13.1%) | |
| 4 | 18 (10.2%) | |
| 5 | 5 (2.8%) | |
| 6 or more | 3 (1.8%) | |
| Secukinumab dosage | ||
| 150 mg/month | 123 (69.9%) | |
| 300 mg/month | 53 (30.1%) | |
| Compliance with FUTURE 1 & 2 inclusion/exclusion criteria | ||
| Yes | 29 (16.5%) | |
| No | 56 (31.8%) | |
| Not known | 91 (51.7%) |
BASDAI = Bath Ankylosing Spondylitis Disease Activity Index, BASFI = Bath Ankylosing Spondylitis functional index, BMI = body mass index, CRP = C-reactive protein, DMARDS = Disease-modifying anti-rheumatic drugs, MRI = magnetic resonance imaging, N = number, NSAID = non steroid anti-inflammatory drugs, PsA = psoriasic arthritis, SD = standard deviation.
Only considered for patients with peripheral arthritis.
Only considered for patients with axial involvement.
The median retention rate of secukinumab was 636 days (95% confidence interval [CI] 542.4–729.5). Six months after the start of secukinumab, global VAS pain modified from 7.14 ± 1.71 to 4.94 ± 2.45 (t = 8.856, P < .001) and CRP plasma levels decreased from 10.77 ± 35.18 to 6.86 ± 12.15 mg/L (t = 1.565, P = .120).
In the bivariate analysis, 2 variables showed statistical differences among patients who were still on treatment with secukinumab and those who stopped it for any reason: the order of administration regarding other biologic therapies and the clinical manifestation of peripheral arthritis. The proportion of patients still on treatment with secukinumab who were naïve to biological therapies was 38.1%, while naïve proportion in patients who stopped treatment was 26.6% (P = .07). In the group of patients who discontinued treatment, the proportion of peripheral arthritis was 77.2%, while in those still on treatment was 92.8%. Table 2 shows the results of the association analysis with all the variables considered relevant. Among numerical variables, the global assessment of axial pain (Spearman’s Rho coefficient -0.213, P = .028) and the bath ankylosing spondylitis functional index (Spearman’s Rho coefficient -0.464, P = .015) showed a significant correlation with the drug retention rate. Among categorical variables, the HLA-B*27 allele was associated with a higher persistence rate of secukinumab (474 ± 238 days [95% CI 400–707] vs 358 ± 237 days [95% CI 239–395] Mann–Whitney’s U test, P = .019). The independent analysis of all the categorical variables through the Kaplan–Meir survival curve demonstrated no difference among any factor except for the presentation of peripheral arthritis and the time of evolution since the diagnosis of PsA. Patients who presented peripheral arthritis had an estimated median drug persistence significantly higher than those without this finding (657 ± 50.8 vs 474.0 ± 129.8, Log Rank P = .004). On the other hand, for those with <3 years of evolution, median estimation was significantly lower than those with 3 to 6 years (542.0 ± 32.6 vs 742.0 ± 74.9, Log Rank P = .018). Table 3 shows the entire list of results of the Kaplan–Meir curve analysis using every categorical variable.
Table 2.
Bivariate analysis of stopping secukinumab or switching to a different therapy in Psoriatic arthritis.
| Variable | No stopping secukinumab (n = 97) | Stopping secukinumab (n = 79) | P value |
|---|---|---|---|
| Sex, n (%) | .224 | ||
| Male | 38 (39.2) | 24 (30.4) | |
| Female | 59 (60.8) | 55 (69.6) | |
| Age onset of diagnosis (years), mean (SD) | 44.94 (12.87) | 44.53 (11.30) | .821 |
| Time of evolution (years) | .751 | ||
| <3 | 47 (48.5) | 36 (45) | |
| 3 to 6 | 24 (25) | 23 (29.1) | |
| >6 | 25 (25.8) | 20 (25.3) | |
| HLA-B27, n (%) | 13 (13.4) | 10 (12.7) | .884 |
| Peripheral arthritis, n (%) | 90 (92.8) | 61 (77.2) | .03 |
| Dactylitis or enthesitis, n (%) | 70 (72.2) | 62 (78.5) | .336 |
| Sacroiliitis n (%) | 15 (15.5) | 15 (19) | .536 |
| Smoking habit, n (%) | .514 | ||
| No smoker | 48 (49.5) | 43 (54.4) | |
| Active or past smoker | 49 (50.5) | 36 (45.6) | |
| BMI, n (%) | .536 | ||
| Normal | 23 (23.7) | 21 (26.6) | |
| Overweight | 31 (32) | 18 (22.8) | |
| Obesity | 16 (16,5) | 20 (25,3) | |
| VAS axial pain scale, n (%) | .141 | ||
| 0 to 4 | 27 (27.8) | 33 (41.8) | |
| 5 to 7 | 6 (6.2) | 3 (3.8) | |
| 8 to 10 | 64 (66) | 43 (54.4) | |
| CRP concentration (mg/L), n (%) | .203 | ||
| <5 | 52 (53.6) | 37 (46.8) | |
| 5 to 10 | 8 (8.2) | 12 (15.2) | |
| >10 | 23 (23.7) | 13 (16.5) | |
| Order of administration of secukinumab, n (%)* | .07 | ||
| Naïve to biological therapies | 37 (38.1) | 21 (26.6) | |
| Second | 36 (37.1) | 43 (54.4) | |
| Third and further | 24 (24.7) | 15 (19) | |
| Secukinumab dose (mg), n (%) | .289 | ||
| 150 | 71 (73.2) | 52 (65.8) | |
| 300 | 26 (26.8) | 27 (34.2) |
BMI = body mass index, CRP = C-reactive protein, N = number, SD = standard deviation, VAS = visual analogic scale.
Order of administration of secukinumab regarding other biologic therapies.
Table 3.
Results of the Kaplan–Meir survival curve analysis with all categorical variables and stratifications of numerical variables.
| Variable | Median estimation | SD | Low 95% CI | High 95% CI | Log Rank (Mantel-Cox) Sig |
|---|---|---|---|---|---|
| Sex | 0.576 | ||||
| Female | 631.0 | 62.7 | 507.9 | 754.0 | |
| Male | 665.0 | 49.9 | 567.1 | 762.8 | |
| Time of evolution (years) | 0.141 | ||||
| <3 | 542.0 | 32.6 | 478.0 | 605.9 | |
| 3 to 6 | 742.0 | 74.9 | 595.1 | 888.8 | |
| >6 | 665.0 | 117.9 | 433.8 | 896.1 | |
| HLA-B*27 | 742.0 | 65.2 | 614.0 | 869.9 | 0.118 |
| BMI | 0.727 | ||||
| Normal | 591.0 | 110.2 | 374.8 | 807.1 | |
| Overweight | 636.0 | 87.4 | 464.5 | 807.4 | |
| Obesity | 928.0 | 214.3 | 507.9 | 1348.0 | |
| Smoking habit | 0.668 | ||||
| Never | 593.5 | 48.8 | 497.9 | 689.2 | |
| Ex-smoker | 600.9 | 40.6 | 521.2 | 680.7 | |
| Active smoker | 621.5 | 105.6 | 414.4 | 828.6 | |
| Peripheral arthritis | 657.0 | 50.8 | 557.3 | 756.6 | 0.004 |
| Dactylitis | 668.3 | 85.8 | 500.1 | 836.5 | 0.661 |
| Enthesitis | 554.6 | 34.7 | 486.5 | 622.8 | 0.152 |
| Dactylitis or enthesitis | 621.5 | 72.9 | 478.5 | 794.6 | 0.820 |
| VAS axial pain scale | 0.494 | ||||
| 0–4 | 809.0 | 104.7 | 603.2 | 1014.3 | |
| 5–7 | 665.0 | 152.1 | 366.8 | 963.1 | |
| 8–10 | 657.0 | 86.4 | 487.5 | 826.5 | |
| CRP concentration (mg/L) | 0.231 | ||||
| <5 | 568.0 | 115.2 | 342.1 | 793.8 | |
| 5–10 | 657.0 | 111.2 | 438.9 | 875.0 | |
| >10 | 724.0 | 107.9 | 530.4 | 953.5 | |
| Order of administration of secukinumab* | 0.735 | ||||
| Naïve to biological therapies | 665.0 | 102.1 | 464.7 | 865.2 | |
| Second | 742.0 | 204.3 | 341.4 | 1142.5 | |
| Third and further | 636.0 | 38.8 | 559.8 | 712.1 | |
| Secukinumab dose (mg) | 0.145 | ||||
| 150 | 638.0 | 68.3 | 504.0 | 771.9 | |
| 300 | 591.0 | 69.2 | 455.1 | 726.8 |
BMI = body mass index, CI = confidence interval, CRP = C-reactive protein, SD = standard deviation, VAS = visual analogic scale.
Order of administration of secukinumab regarding other biologic therapies.
In the Cox regression analysis, the following variables were included: sex, time of evolution, age at onset of diagnosis, HLA-B*27, the order of administration of secukinumab, the dose of secukinumab administered, CRP concentration, VAS of axial pain level, body mass index, the presence of sacroiliitis, peripheral arthritis and the combination of dactylitis and enthesitis. The dependent variable was the time (days) since secukinumab was first administered until its suspension or until the end of the follow-up. Presence of peripheral arthritis (hazard ratio 0.424 [95% CI 0.213–0.847, P = .015]) and a time of evolution > 6 years (hazard ratio 0.468 [95% CI 0.225–0.975, P = .043]) were the 2 variables that showed a significant influence on the drug retention rate. The complete results of the Cox regression analysis are shown in Table 4.
Table 4.
Multivariate analysis of stopping secukinumab or switching to a different therapy in the cohort of patients with Psoriatic arthritis.
| Variable | HR (95% CI) adjusted | P value |
|---|---|---|
| Sex (ref. Male) | 0.959 (0.515–1.787) | .895 |
| Age onset of diagnosis (years) | 0.987 (0.962–1.014) | .345 |
| Time of evolution (years) (ref. <3) | ||
| 3 to 6 | 0.966 (0.475–1.967) | .925 |
| >6 | 0.468 (0.225–0.975) | .043 |
| HLA-B27 (ref. No) | 0.510 (0.225–1.152) | .105 |
| Peripheral arthritis (ref. No) | 0.424 (0.213–0.847) | .015 |
| Dactylitis or enthesitis (ref. No) | 1.626 (0.830–3.185) | .156 |
| Sacroiliitis (ref. No) | 1.298 (0.669–2.519) | .441 |
| Smoking habit (ref. No) | 0.768 (0.460–1.282) | .313 |
| BMI (ref. Normal) | ||
| Overweight | 0.614 (0.279–1.350) | .225 |
| Obesity | 0.874 (0.415–1.839) | .722 |
| VAS axial pain scale (ref. 0 to 4) | ||
| 5 to 7 | 1.113 (0.567–2.183) | .756 |
| 8 to 10 | 0.301 (0.079–1.147) | .079 |
| CRP concentration (mg/L) (ref. < 5) | ||
| 5 to 10 | 0.787 (0.284–2.177) | .644 |
| >10 | 0.900 (0.420–1.927) | .786 |
| Order of administration of secukinumab (ref. naïve)* | ||
| Second | 1.301 (0.567–2.183) | .478 |
| Third and further | 1.099 (0.501–2.411) | .813 |
| Secukinumab dose (mg) (ref. 150) | 0.610 (0.336–1.108) | .104 |
Cox regression modelization through the intro method. Bold value if statistical significance (P < .05).
BMI = body mass index, CI = confidence interval, CRP = C-reactive protein, HR = hazard ratio, VAS = visual analogic scale.
Order of administration of secukinumab regarding other biologic therapies.
Discontinuation of secukinumab, which occurred in 77 patients (23%), was due to the following reasons: Lack of efficacy before the first 6 months in 46 (58.2%), lack of efficacy after the first 6 months in 24 (30.3%), adverse effects in 7 (8.8%), However, no patient had to be admitted to the hospital due to an adverse effect, and no deaths were registered.
4. Discussion
According to our results, in a real-world data scenario, the median retention rate of secukinumab in patients with PsA is 1.74 years. While drug persistence is a surrogate indicator of effectiveness, our study identified a significant reduction in pain intensity as well as plasma CRP concentration at 6 months. On the other hand, among the reasons for treatment discontinuation, no serious causes were identified, and mild adverse events leading to discontinuation were rare. It is interesting to note that only 16,5% of the patients who received treatment in our cohort, could have been included in the 2 pivotal trials of secukinumab for this indication.
Our study has limitations that we believe should be considered prior to a complete interpretation of the results. Firstly, our study is a retrospective study and based exclusively on the review of medical records. As expected, the availability of clinical, imaging, and laboratory information was not homogeneous, which could affect the statistical analysis, especially the multivariate regression analysis. In the same sense, the study’s multicenter nature implies that the interpretation of non-objective complementary tests is subject to the risk of interobserver variability. Furthermore, it is worth mentioning that our cohort’s follow-up period was 3 years, a shorter period than the mean of studies with aTFN, aIL12/23 and aIL-17 drugs in PsA.[16] Although there are no prospective drug persistence studies of secukinumab in PsA to establish comparisons of follow-up time, it is possible that the length of our observation period leads to the underestimation of the actual persistence rate of the drug. Finally, we do not mention any difference regarding the 2 doses of secukinumab used because the authors were unable to ensure that any dosage of 150 mg/month was modified to 300 mg/month or -much less likely- that the opposite occurred during the follow-up. Although the bivariate study showed certain differences in the drug retention rate in favorable to the 300 mg/month dose vs 150 mg/month (473.0 ± 270.4 days vs 362.7 ± 231.5, resp.; t = 2.588, P = .011), in the regression model this variable was not of major relevance.
Our study’s main strengths are its multicenter nature and its real-world data origins. We have included patients treated in 4 of the largest tertiary hospitals in Madrid, all of which have a specific PsA clinic, the geographical distribution of these hospitals, the volume of patients treated for this pathology, and the number of biologic therapy prescriptions administered in these centers ensure a representative population of the patients receiving biologic therapy as treatment in our setting. As expected in a real-world evidence scenario, patients who were included in our cohort did not necessarily meet the inclusion/exclusion criteria of the 2 pivotal clinical trials developed prior to the launch of secukinumab as an approved therapy for the treatment of PsA. Although insufficient information was available to assess the compatibility criteria in all patients, we suspect that the described ratio (2:1) of patients who did not meet/met inclusion and exclusion criteria applies to all of our patients. Real-world evidence studies are of greater value to expose the experience of these patients who could not have participated in the pivotal clinical trials, but they do not allow validating the results in the population. Therefore, the purpose of the present study was to expose the retention rate of secukinumab in our cohort to identify a specific patient profile that could benefit from this treatment.
Our results are difficult to contrast with the information available in scientific literature, given that it focuses on a single therapy to determine conditioning factors that modify its therapeutic drug persistence. Ruiz-Villaverde et al recently described a cohort of 64 patients with PsA treated with secukinumab in real-world conditions to identify characteristics that could be associated with increased drug persistence.[17] According to their results, secukinumab had a mean persistence rate of 130 weeks with no increase in reference to any particular patient profile. Also, recently, Klavdianou et al reported the efficacy and safety of secukinumab in patients with PsA.[18] According to their data - from 75 patients followed up for almost 2 years - the persistence rate at the end of follow-up was 64%, with no difference regarding patient profiles or even previous biological therapy. However, much more information is available on the comparative persistence rate of secukinumab with other biologic therapies in series of patients with psoriasis and PsA. Recently, Oelke et al, in a biologic drug-persistence study including more than 1500 patients with PsA based on a claims database, demonstrated that secukinumab had the lowest discontinuation rate (36.5%) and the highest persistence over 12 months compared to aTNF treatments such as adalimumab, etanercept, certolizumab pegol, and golimumab.[19] In a recently published Austrian study of patients with psoriasis,[20] biologic drug persistence was found to be decreased in second versus first lines of treatment and was lower in women. Considering only naïve patients, ustekinumab, secukinumab, and ixekizumab treatments had significantly longer persistence rates vs anti-TNFs at 12 months and beyond. An interesting finding of this study was that the diagnosis of PsA was associated with a higher drug persistence rate than that of patients with psoriasis alone. The superiority of secukinumab in terms of drug persistence compared to adalimumab when administered as first-line therapy has been demonstrated in a prospective Swedish cohort. Regardless of whether they were naïve or non-naïve patients to other biologic therapies, secukinumab had a lower persistence rate in women, patients with recent disease onset, and in patients with axial forms.[21] Regarding the latter, this study determined that the risk of discontinuation of secukinumab was 1.2 (95% CI 1.01–1.44) relative to that of adalimumab in patients with axial involvement. This finding would correlate positively with the drug’s increased persistence rate in patients with primarily peripheral forms of the disease described in our study.
Most of the data used to report the results of therapy changes come from real-life studies. In PsA, persistence rates have been significantly lower regarding second biologic therapies than with first.[22] In our cohort, <20% of patients met inclusion criteria for pivotal secukinumab trials. This low proportion is consistent with that described in 2 studies based on real-life data in patients with psoriasis.[23,24]
To our knowledge, this is the largest cohort study of PsA patients based on real-life data on secukinumab persistence rate. Our results confirm the drug’s efficacy and safety as surrogate measures of persistence. It also suggests that peripheral forms of PsA would have the highest drug persistence rate.
Author contributions
All authors contributed to the study conception, design, material preparation, data collection and analysis. All authors read and approved the final manuscript.
Conceptualization: Marta Valero-Expósito, María Martín-López, Carlos Guillén-Astete, Beatriz Joven, Carolina Merino-Argumanez, Valentina Emperiale, Jose Campos, Ana Pérez, Javier Bachiller-Corral.
Formal analysis: Marta Valero-Expósito, María Martín-López, Carlos Guillén-Astete, Beatriz Joven, Carolina Merino-Argumanez, Valentina Emperiale, Jose Campos, Ana Pérez, Javier Bachiller-Corral.
Visualization: Marta Valero-Expósito, María Martín-López.
Writing – original draft: Marta Valero-Expósito, María Martín-López, Carlos Guillén-Astete, Beatriz Joven, Carolina Merino-Argumanez, Valentina Emperiale, Jose Campos, Ana Pérez, Javier Bachiller-Corral.
Writing – review & editing: Marta Valero-Expósito, María Martín-López, Carlos Guillén-Astete, Beatriz Joven, Carolina Merino-Argumanez, Valentina Emperiale, Jose Campos, Ana Pérez, Javier Bachiller-Corral.
Supplementary Material
Abbreviations:
- CI =
- confidence interval
- CRP =
- C-reactive protein
- DMARDs =
- disease-modifying drugs
- PsA =
- psoriatic arthritis
- VAS =
- visual analogic scale
The datasets generated during and/or analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.
The authors declare that some of the information used for the preparation of this manuscript was previously published in abstract form at the 2019 EULAR international congress. Ann Rheum Dis, volume 78, supplement 2, year 2019, page A1862.
Supplemental Digital Content is available for this article.
Dr Valero, Dr Martín, Dr Guillén, Dr Joven, Dr Merino, Dr Campos, Dr Pérez and Dr Bachiller declare that they have received fees for the provision of consultancy services or lectures on behalf of Novartis, the pharmaceutical company responsible for the distribution of secukinumab in Spain. None of the authors have any contractual relationship with or ownership of stocks in Novartis.
The authors declare that no external funding was provided for the implementation of this study. The costs incurred by the study itself and the time invested by the authors did not generate any financial or non-monetary compensation.
The present study was approved by the corresponding ethics committees of all participating hospitals.
The authors have no conflicts of interest to disclose.
How to cite this article: Valero -Expósito M, Martín-López M, Guillén-Astete C, Joven B, Merino-Argumanez C, Emperiale V, Campos J, Pérez A, Bachiller-Corral J. Retention rate of secukinumab in psoriatic arthritis: Real-world data results from a Spanish multicenter cohort. Medicine 2022;101:36(e30444).
Contributor Information
Marta Valero-Expósito, Email: martavaleroex@yahoo.es.
Beatriz Joven, Email: beatrizjoven@hotmail.com.
Carolina Merino-Argumanez, Email: merinocarol11@gmail.com.
Valentina Emperiale, Email: vemperiale@gmail.com.
Jose Campos, Email: josecampose@gmail.com.
Ana Pérez, Email: aperezalcala@yahoo.es.
Javier Bachiller-Corral, Email: javierbachiller@gmail.com.
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