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Abstract
Background Sex differences in phenotype presentation, disease trajectory and treatment response in psoriatic arthritis (PsA) have been reported. Nevertheless, whether classes of targeted therapies differentially affect men and women with PsA remains unclear.
Objectives To assess the effect of sex on the long-term persistence of each class of targeted therapies in PsA.
Methods This nationwide cohort study involved the administrative healthcare database of the French health insurance scheme linked to the hospital discharge database. We included all adults with PsA who were new users of targeted therapies (not in the year before the index date) during 2015–2021 and studied all treatment lines during the study period. Persistence was defined as the time from treatment initiation to discontinuation and was estimated by the Kaplan-Meier method. Comparison of persistence by sex involved multivariate frailty models with conventional synthetic disease-modifying antirheumatic drugs and prednisone as time-dependant variables.
Results We included 14 778 patients with PsA who were new users of targeted therapies: 8475 (57%) women (mean age 50±13 years; 15 831 lines), 6303 (43%) men (mean age 51±13 years; 10 488 lines). Overall, 1-year persistence was 52% for women and 62% for men and at 3 years it was 27% and 39%, respectively. After adjustments, persistence was lower for women than men for inhibitors of tumour necrosis factor (TNFi) (adjusted HR (HRa) 1.4, 99% CI 1.3 to 1.5) and interleukin 17 inhibitor (IL17i) (HRa 1.2, 99% CI 1.1 to 1.3) but not IL12/23i (HRa 1.1, 99% CI 0.9 to 1.3), IL23i (HRa 1.1, 99% CI 0.7 to 1.5) or Janus kinase inhibitor (JAKi) (HRa 1.2, 99% CI 0.9 to 1.6).
Conclusion The treatment persistence was lower for women than men for TNFi and IL17i but not for IL12/23i, IL23i or JAKi.
- Arthritis, Psoriatic
- Biological Therapy
- Tumor Necrosis Factor Inhibitors
Data availability statement
Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental information. All relevant data are reported in the article. Additional details can be provided by the corresponding author upon reasonable request.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
Psoriatic arthritis is a heterogeneous condition.
Sex differences in phenotype presentation, disease trajectory and treatment response in PsA have been reported.
WHAT THIS STUDY ADDS
In PsA, treatment persistence was lower for women than men, but with different magnitude by therapeutic class.
The sex difference in persistence was significant for inhibitors of tumour necrosis factor and interleukin 17 inhibitor (IL17i) but not for IL12/23i, IL23i or Janus kinase inhibitor.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
This finding highlights the need for sex-based and gender-based studies to better understand the underlying mechanisms.
Head-to-head studies with sex-stratified analyses are needed to tailor patient management and enable personalised medicine.
Introduction
Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory rheumatic disease that combines articular and periarticular manifestations with extramusculoskeletal manifestations. It affects 0.1%–0.2% of the general population and up to 20% of patients with psoriasis.1–4 Although early studies tended to show a male predominance of PsA, a change in the sex distribution to a female predominance was reported over the last decade.5 In the French health insurance database, the female-to-male ratio was recently reported as 1.2.6 Furthermore, PsA seems to affect male and female patients differently, resulting in sex-related and gender-related differences in clinical presentation and disease course but also response to treatment.5 7 8
With the rapid advent of biologics over the past two decades, the therapeutic armamentarium for PsA has expanded considerably. Not only inhibitors of tumour necrosis factor (TNFi) but also interleukin 12/23 (IL12/23i), IL17 (IL17i), IL23 (IL23i) and Janus kinase inhibitor (JAKi) are now recommended for moderate-to-severe PsA when conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) fail to control disease or are not tolerated.9–12 These treatments have been found effective and safe in various studies but may be discontinued because of primary or secondary failure or adverse events.13
Treatment persistence is an important real-world outcome for assessing the total value of a drug and can be considered a composite of efficacy and safety as well as patient satisfaction or preference and adherence.14 Differences in persistence of targeted therapies by sex have been reported. Nevertheless, although a specific study of sex differences could have important implications for achieving the ambitious goals of personalised medicine, existing studies have mostly assessed sex in addition to other predictors of drug efficacy and are limited by small sample sizes.15 16 Several cohort studies and registries have reported sex-related disparities in the TNFi response in PsA, with lower persistence for women than men.17 18 However, no formal conclusions can be drawn from these studies. Indeed, similar to what was reported for randomised controlled trials, patients included in national cohorts and registries may not be representative of the ‘real life’ exposed population.19 These studies are limited by the number of inclusion and exclusion criteria, which may lead to a particular selection of the study population and are also subject to bias related to lost to follow-up. Equivalent signals concerning the impact of sex on the IL17i response seem to be emerging but remain to be confirmed.20 Few studies have included the most recently marketed molecules, and the existing data on other ILi in PsA is sparse.5 21 Finally a recent study of JAKi suggested no sex effect on therapeutic persistence in PsA, but the study was based on a post hoc analysis of data pooled from two patient populations (TNF-naïve and TNF-inadequate responders).22 Therefore, we need a specific study of whether different targeted therapy classes affect men and women with PsA differently in a ‘real-life’ patient cohort.
The current study evaluated the effect of sex on the long-term persistence of each targeted therapeutic class in PsA.
Methods
Data source and study design
This nationwide cohort study was based on data from the French national health insurance database (Système National des Données de Santé (SNDS)).23 The database contains individualised anonymous health data and covers 99% of the French population (> 67 million individuals). Each person is identified by a unique code. The French healthcare system provides universal and mandatory coverage: all citizens have free, equal and universal access to healthcare for chronic diseases. As previously described, the SNDS contains exhaustive data for all reimbursements for health-related expenditures and outpatient medical care and nursing care prescribed or performed by healthcare professionals, together with sociodemographic data (including year of birth, sex, area of residence, degree of social deprivation in the geographic area24 and vital status). The database also includes data on all pharmacy-dispensed medications (number of units and date of reimbursed drug dispensation); date and nature of medical and paramedical interventions; information on patient eligibility for fully reimbursed care (long-term diseases) related to severe, costly chronic diseases, such as moderate-to-severe PsA, with codes assigned according to the International Classification of Diseases, 10th Revision (ICD-10); and detailed medical information concerning all admissions to French public sector and private sector hospitals (dates of hospital admission and discharge; ICD-10 code on discharge; medical procedures performed in the hospital; and costly drugs, such as biologics, administered in hospital).23 25 This large database has been used for several pharmacoepidemiological studies.26–28
Study population and exposure definition
All adults (≥18 years old) with PsA registered in the SNDS between 1 January 2015 and 30 June 2021 were eligible for inclusion. Adults with PsA were identified by a specific ICD-10 code (M07, except M07.4 and M07.5) according to an algorithm previously published.6 This study’s start date was chosen because it corresponded to the widest use of the specific ICD-10 code for PsA in France. Then, patients with at least one prescription for a targeted therapy were identified. Next, we selected those who were new users of the targeted therapy, defined as those who had not filled a prescription for one of the drugs for 1 year. We considered all treatment lines over the study period. Targeted therapies considered included etanercept, infliximab, adalimumab, certolizumab and golimumab as the TNFi; ustekinumab as the IL12/23i; secukinumab, ixekizumab and brodalumab as the IL17i; guselkumab, tildrakizumab and risankizumab as the IL23i; and tofacitinib and upadacitinib as the JAKi. Apremilast, which has a special place in the therapeutic strategy for PsA, has not been studied here. Drugs were identified in outpatient and hospital discharge databases. The index date was the date of initiation of the treatment line during the study period. Patients were followed until 31 December 2021.
Outcome
The primary endpoint was persistence of a targeted therapy (originator and biosimilar), defined as the time between treatment initiation and discontinuation. We defined the discontinuation of treatment as a period of more than 60 days without filling a prescription for the same treatment after the period covered by the previous prescription, regardless of the molecule used. The period covered by a prescription was 28 days for most TNFi, IL17i and JAKi agents, 56 days for infliximab and 84 days for IL12/23i and IL23i. These durations are based on the frequency of administration of the different molecules. If a switch to another targeted therapy occurred during the previous treatment exposure period, its discontinuation date corresponded to the date of new targeted therapy delivery.
Covariables
We collected data on basic demographics, including age, sex, complementary universal health coverage and French deprivation index (geographical indicator of social disadvantage specifically adapted to health studies of the French population24), inflammatory diseases associated with PsA (active skin psoriasis, inflammatory bowel disease (IBD), uveitis), variables used to calculate the Charlson Comorbidity Index (CCI) adapted to the SNDS29 and other comorbidities (mood disorders, proxy of tobacco use or alcohol intake, morbid or complicated obesity). We also collected the number of consultations with a rheumatologist and a dermatologist during the 2 years before the index date, the use of symptomatic treatments (weak and strong opioids, analgesics and corticosteroids injections) during the 2 years before the index date, and information available in our database on hormonal factors for women (pregnancies with live birth, use of contraception or hormone replacement therapy). These covariables are defined in online supplemental table 1. Other drugs used as add-on therapies to targeted therapies were studied: csDMARDs (methotrexate, leflunomide and sulfasalazine), non-steroidal antiinflammatory drugs (NSAIDs) and prednisone (the most commonly prescribed corticosteroid for PsA in France). Therapeutic coprescription (combination of csDMARDs, NSAIDs or prednisone with a targeted therapy) at baseline was defined as a period of ≤30 days between reimbursements of the two treatments.
Supplemental material
During follow-up, we compiled the vital status and exposure to csDMARDs and prednisone.
Statistical analyses
Categorical variables are reported as number (percentage). Quantitative variables are reported as median with IQR or mean±SD. There were no missing data in our database.
Patients were followed from the index date to 31 December 2021. All the therapeutic lines were identified during the follow-up study. The duration of therapeutic lines was assessed as defined above. Patients were censored in case of targeted therapy discontinuation/switch, death or 31 December 2021, whichever came first. We also reported the proportion of patients initiating targeted therapy as first-line therapy for each therapeutic class, by sex and by semester (6-month period) during the study period.
Changes in treatment persistence over time were estimated for each sex for all targeted therapies together and for each therapeutic class separately by using the Kaplan-Meier method. We used multivariate frailty models, extensions of Cox proportional-hazard models allowing for non-independence of data (multiple lines of treatments for the same patient), to estimate HRs associated with treatment discontinuation and their CIs.30 Given the multiple comparisons (five therapeutic classes) and to control for risk of type 1 error (alpha inflation), we applied a Bonferroni adjustment: p≤0.01 was considered significant and 99% CIs were estimated. We adjusted for various potential confounders collected at the index date: age, morbid or complicated obesity, alcohol intake and smoking (proxy), CCI, and, to approach PsA activity and severity, number of hospitalisations for PsA, number of consultations with a rheumatologist, and csDMARD, prednisone and NSAID use in the 2 years before the index date but also coprescriptions of specific drugs at the index date. Treatments used as add-on therapies to targeted therapies during follow-up (csDMARDs and prednisone) were considered time-dependent variables and were used as adjustment variables in the multivariate models. Similar analyses were performed among patients receiving only first-line therapy.
We performed prespecified subgroup analyses for (1) patients with and without active skin psoriasis (at least four deliveries of topical treatments within 2 years) and (2) patients<51 years old or ≥51 years (average age of menopause in France31).
To assess the sensitivity of the estimated HRs with respect to several possible models, we performed the following additional analyses: (1) censoring follow-up at the time of a therapeutic switch, death or 31 December 2021, whichever came first, and not at the time of the therapeutic sequence discontinuation as in the main analysis to account for discontinuation of treatment due to possible remission; (2) defining treatment discontinuation as >90 days without filling a prescription for the same treatment after the period covered by the previous prescription; and (3) modifying the new-user definition to patients who had not filled a prescription for a targeted therapy for 5 years before the index date (and not 1 year as in the main analysis).
Analyses were performed with SAS Enterprise Guide V.7.1.
Results
Description of the cohort population
During the study period, we identified 14 778 patients with PsA who were new users of targeted therapies: 8475 (57%) were women and 6303 (43%) men (table 1). Each patient took a mean of 1.8±1.1 therapeutic lines (range 1–10) with a mean duration of 1.6±1.5 years (mean age 50.5±13.1 years; follow-up 1.8±1.6 years). We studied 26 319 therapeutic lines; specifically, we analysed the following treatment lines in women: 60% (9462) TNFi, 24% (3762) IL17i, 10% (1639) IL12/23i, 3% (392) IL23i and 4% (576) JAKi. We analysed the following treatment lines in men: 59% (6192) TNFi, 23% (2433) IL17i, 11% (1170) IL12/23i, 4% (406) IL23i and 3% (287) JAKi. Details of each molecule (whatever the line and first line) are shown in online supplemental table 2.
Characteristics of the cohort with psoriatic arthritis (PsA) overall and by sex
Online supplemental figure 1 reports the proportion of patients initiating first-line targeted therapy for each therapeutic class by sex each semester during the study period. The proportion of initiation of each therapeutic class was similar for both sexes: during the study period, both sexes exhibited a decrease in initiation of TNFi in favour of more recent classes such as IL17i, IL12/23i and IL23i, although TNFi remained the most frequently prescribed therapeutic class as first line.
Overall, 26% of patients had not received any csDMARD in the previous 2 years (24% of women, 28% of men) (table 1). At inclusion, associated csDMARDs (mainly methotrexate) were prescribed to 45% of patients (46% of women, 43% of men) and during follow-up to 49% of patients (51% of women, 46% of men). The proportions of associated inflammatory diseases and comorbidities (measured by the CCI) were similar for women and men. Finally, the use of NSAIDs and prednisone as well as opioids and corticosteroids injections was higher for women than men.
Persistence of biologics
During follow-up, 63% (9243) of patients discontinued their treatment: 68% of women and 56% of men. Kaplan-Meier survival analyses revealed an overall persistence of targeted therapies of 52% for women and 62% for men in the first year of treatment whatever the therapeutic line (table 2). This persistence decreased over time: 35% at the end of the second year and 27% at the end of the third year for women and 47% at the end of the second year and 39% at the end of the third year for men. Figure 1 summarises the Kaplan-Meier analyses for each therapeutic class by sex whatever the therapeutic line: treatment persistence was lower for women than men but with a different magnitude by therapeutic class.
Kaplan-Meier estimates of persistence overall and for each therapeutic class, by sex. ILi, interleukin inhibitor; JAKi, Janus kinase inhibitor; TNFi, tumour necrosis factor inhibitor.
Persistence rates (%) for targeted therapies at 1, 2 and 3 years of follow-up by sex (Kaplan-Meier)
Comparison of biologic persistence by sex
The results of the main analysis are shown in table 3. After multivariate frailty model analysis and adjustment on time-dependent covariables (csDMARDs, prednisone), persistence was lower for women than men for TNFi (HRa 1.4, 99% CI 1.3 to 1.5) and IL17i (HRa 1.2, 99% CI 1.1 to 1.3) but not for IL12/23i (HRa 1.1, 99% CI 0.9 to 1.3), IL23i (HRa 1.1, 99% CI 0.7 to 1.5) or JAKi (HRa 1.2, 99% CI 0.9 to 1.6).
Multivariate frailty analysis of persistence of targeted therapies by sex and adjusting for time-dependent covariables (conventional synthetic disease-modifying antirheumatic drugs and prednisone)
Subgroup and sensitivity analyses
The results of the subgroup analyses (patients with and without active psoriasis, patients <51 and ≥51 years) were similar to the main analysis but with slightly higher HRa for patients with active psoriasis and those <51 years (figure 2). Sensitivity analyses results were consistent with those of the main analysis (online supplemental figure 2). Among only patients with first-line therapy, the results were similar: persistence was lower for women than men for TNFi (HRa 1.5, 99% CI 1.4 to 1.6) and IL17i (HRa 1.4, 99% CI 1.2 to 1.6) but not IL12/23i (HRa 1.2, 99% CI 1.0 to 1.4), IL23i (HRa 1.6, 99% CI 0.7 to 3.3) or JAKi (HRa 1.0, 99% CI 0.5 to 1.8). Other factors associated with reduced persistence were previous exposure to targeted therapy, presence of comorbidities, morbid or complicated obesity, smoking, hospitalisation related to PsA and number of visits with a rheumatologist within 2 years before the index date (proxy for rheumatic severity), exposure to a csDMARD within 2 years before the index date, coprescription of NSAIDs or prednisone at the index date and coprescription of prednisone during follow-up. Factors associated with higher persistence were age and coprescription of csDMARDs during follow-up (online supplemental table 3).
Persistence of targeted therapies by sex (women vs men) for patients with and without associated active psoriasis and those younger and older than 51 years. Adjusted for age, morbid or complicated obesity, smoking (proxy), alcohol (proxy), Charlson Comorbidity Index, hospitalisation for psoriatic arthritis within 2 years, consultations with a rheumatologist within 2 years, csDMARDs at index date, NSAIDs at index date, prednisone at index date, csDMARDs within 2 years, NSAIDs within 2 years and prednisone within 2 years, and then on prednisone and csDMARDs as time-dependent variables. A Bonferroni correction was applied: the 99% CIs are indicated. HRa, adjusted HR; ILi, interleukin inhibitor; JAKi, Janus kinase inhibitor; TNFi, tumour necrosis factor inhibitor.
Discussion
In this nationwide study involving 14 778 new users of targeted therapies with PsA, we assessed the effect of sex on the persistence of different therapeutic classes in an unselected population. In the first year, overall persistence for targeted therapies, whatever the treatment line, was 52% for women and 62% for men. Persistence decreased markedly over time for women and men to 27% and 39%, respectively, at the end of the third year, although in varying proportions by therapeutic class. After adjustment, persistence was lower for women than men for TNFi and IL17i but not IL12/23i, IL23i or JAKi.
Our results are important because this is the largest study that specifically investigated the effect of sex on treatment persistence of different classes of targeted therapies in PsA in real-world settings. Our study confirms the lower persistence of TNFi in women than men with PsA, both bio-naïve and bioexperienced patients, reported in some studies.17 32–34 Regarding other targeted therapies, few studies have specifically addressed the impact of sex in PsA and most have investigated the treatment persistence of all pooled bDMARDs, which may explain discordant results depending on the population and treatments included: female sex was found associated with poor treatment persistence in some studies35 36 but not in another.15
In our analysis, the sex difference in persistence also concerned IL17i. This result agrees with a recent prospective, multicentre study of 608 patients with PsA finding that male sex seemed protective against secukinumab discontinuation.20 Of note, we found no statistically significant difference in treatment persistence between women and men for other targeted therapies (although a trend was observed for IL12/23i). Our results are similar to those of a real-world study of psoriatic patients finding that male sex affected persistence significantly in patients receiving TNFi but not IL12/23i.37 A recent post hoc analysis based on the PsABio study revealed better persistence for male than female patients with PsA initiating IL12/23i or TNFi. However, the two therapeutic classes were not studied separately, and the analysis of this outcome was not adjusted.38 Very few studies have included these new molecules in their analyses, but the conclusions in psoriatic patients seem consistent with ours: no significant impact of sex on persistence of IL23i21 and JAKi.22 Nevertheless, it should be borne in mind that the number of patients treated with these molecules remains small, and further studies will be needed in the future.
Several factors can be suggested to explain this sex effect. First, the phenotype of not only the rheumatism (axial or peripheral, oligoarticular or polyarticular involvement) but also the activity and severity of the disease seem to differ between men and women. Indeed, men with PsA are more likely to experience axial involvement than women.7 Women with PsA tend to have greater disease activity and lower physical function scores than men.7 39 In addition, biological and molecular mechanisms underlying the pathogenesis of arthritis pain show important sex differences.40 In this direction, we found that women had higher healthcare consumption than men, with more use of csDMARDs, NSAIDs and prednisone but also more analgesics, corticosteroids injections, hospitalisation related to PsA and consultations with a rheumatologist. Furthermore, women seem to have a more pronounced innate and acquired immune response than men.41 This finding may account for a difference in immunogenicity, the propensity of a therapy to generate an immune response and to form antidrug antibodies and could explain some of the variation in the sex effect by therapeutic class. Indeed, immunogenicity has been found to vary considerably by therapeutic class: greater with TNFi, lower with ILi and almost absent with JAKi.42 43 Finally, there is a potential but difficult-to-quantify impact of gender in our study, a term to be distinguished from ‘sex’.5 44 Sex refers to the biological characteristics associated with being male or female; gender is a sociocultural construct that refers to the social norms that determine roles, relationships and position in society.5 40 The difference observed in our study could be related to disparities in healthcare-seeking behaviour due to gender norms. In particular, this situation could lead to a different perception and lower reporting of adverse events in men than women, as has been shown in pharmacovigilance databases.45 46 In addition, as reported in a systematic review, women may have lower levels of adherence to therapies than men.47 Nevertheless, this adherence difference may tend to disappear for molecules with longer intervals between administration, such as IL12/23i and IL23i, or for treatments that are easier to administer, such as JAKi. Finally, this gender effect could also generate different expectations for women and men by patients and physicians, especially with regard to daily functions and skin involvement, which would explain in part the differences in persistence between therapeutic classes. Indeed, treatment persistence in psoriasis was recently found better with IL12/23i, IL23i and IL17i than TNFi.48 49
This study has limitations. First, we defined drug exposure based on healthcare reimbursement data, which is not necessarily equivalent to days of use. However, adherence rates are typically higher for biologics than other treatment categories.50 Second, although we adjusted for baseline characteristics known to affect treatment persistence and coprescription therapy as time-dependent variables, the presence of residual confounding effects cannot be excluded. Our analyses are limited by data availability for some factors, particularly information on disease phenotype and rheumatic activity/severity (although we attempted to approximate these parameters with available data). There may also be potential biases linked to the centre or to prescribing habits, which could not be completely controlled in this study. Additionally, some of the drugs studied came to the market years ago and others more recently, which may account for a change in persistence. However, our study period was restricted to a recent timeframe (2015–2021), and the proportion of initiation of each therapeutic class was similar for both sexes. Moreover, we decided not to include apremilast. According to European Alliance of Associations for Rheumatology recommendations, this treatment is recommended only when csDMARD therapy has failed and bDMARDs and JAKi are not appropriate in patients with relatively mild disease.9 Unlike other targeted therapies, it can be initiated by non-hospital physicians, is sometimes administered in combination with other bDMARDs and requires different follow-up, which could lead to selection bias. Our study is based on a population of French residents, which may limit its extrapolability to other countries. Nevertheless, we have previously reported that our study population presented similar characteristics to those of patients with moderate-to-severe PsA described not only in the UK but also in Australia, Canada or the USA.6 Our definition of a treatment discontinuation after a 60 days period following the period covered by the last dispensation could be discussed, as in clinical practice temporary suspensions due to adverse events could be longer. However, the two sensitivity analyses, for example, (1) with a 90 days period and (2) with a follow-up until a therapeutic switch showed similar results, making us confident in our results. It should be noted that persistence rates reported here are quietly lower than those observed in other studies.20 51 This observation could be due to potential selection bias, which could limit the extrapolation of literature data. As reported for randomised clinical trials, for registries and national cohorts, the representativeness of the patients included may be questioned. Indeed, these studies have several inclusion and exclusion criteria, which may lead to a particular selection of the study population.19 In addition, they are also subject to biases related to lost to follow-up, country’s healthcare organisation and doctor–patient relationship. In contrast, our study was based on a large-scale, exhaustive analysis of reimbursement data from a non-selected population, with no lost to follow-up, which avoids these biases. Finally, the database analysed in this study did not specify the reasons why a patient stopped filling prescriptions for a biologic: loss of efficacy, occurrence of a side effect, presence of comorbidities or extrinsic factors such as a wider range of treatment options.52
This study has several strengths. Our cohort involved a large number of patients from a national database, with a data quality and consistency plan ensuring homogeneous data processing (quality control at the time of data acquisition from electronic exchanges, at the time of data entry in a data processing centre and after coding before integration in the national data warehouse) and with information captured during routine medical care.23 This framework minimises selection bias. Furthermore, we used a new-user design53 to more accurately estimate the persistence and control channelling bias. Importantly, the targeted therapies studied are recommended treatments for moderate-to-severe psoriatic disease and that in France, each physician is free to choose the treatment labelled for PsA.9 However, except in minority cases where an extramusculoskeletal manifestation (very active psoriasis, IBD, severe or repeated acute anterior uveitis) guides the prescriber’s choice, no factor is today likely to influence this prescription at population level. Moreover, we controlled for the effect of corticosteroids and csDMARDs at baseline and throughout the follow-up (time-dependent variables) to adequately compare treatment persistence in each therapeutic class prescribed as first line but also whatever the line by sex. We also limited classification bias by using a reproducible, well-accepted definition of drug persistence.54 Finally, several sensitivity analyses were performed and their results supported the integrity of our main results.
Conclusion
Beyond confirming a lower persistence of TNFi for women than men with PsA, we found that this difference also concerned IL17i but was not significant for IL12/23i, IL23i or JAKi. This finding highlights the need for sex-based and gender-based studies to better understand the underlying mechanisms but also for head-to-head studies with sex-stratified analyses to optimise the management of PsA and achieve the ambitious goal of personalised medicine in the coming years.
Data availability statement
Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental information. All relevant data are reported in the article. Additional details can be provided by the corresponding author upon reasonable request.
Ethics statements
Patient consent for publication
Ethics approval
The protocol for this study received a favourable opinion from an independent ethics committee (Comité d'expertise pour les recherches, les études et les évaluations dans le domaine de la santé) and specific approval was obtained to conduct this study from the French data protection agency (Commission nationale de l’informatique et des libertés: MLD/MFI/AR2010413). As the data were pseudonymised, no consent was specifically required from the patients included in this study. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology reporting guidelines.
Acknowledgments
We thank Laura Smales for English editing.
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Twitter @LauraPnVg
ES and PC contributed equally.
Correction notice This article has been updated since it was first published online. Under the 'What this study adds' section of the key messages box, the second line has been updated from 'The sex difference in persistence was significant not only for inhibitors of tumour necrosis factor and interleukin 17 inhibitor (IL17i) but not for IL12/23i, IL23i or Janus kinase inhibitor' to 'The sex difference in persistence was significant for inhibitors of tumour necrosis factor and interleukin 17 inhibitor (IL17i) but not for IL12/23i, IL23i or Janus kinase inhibitor'.
Contributors Study idea and concept: LPV, ES and PC. Data collection: LPV and LP. Data analysis: LPV and LP. LPV drafted the article and acts as guarantor of the study. All authors interpreted the results, critically revised the manuscript and approved the final version.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests LPV received a subsidy from Novartis to attend a congress. LP and ES have no conflict of interest to declare. PC has received consulting fees from Abbvie, Amgen, Pfizer, Roche-Chugai, BMS, MSD, UCB, Novartis, Janssen, Lilly, Galapagos, Celgene (less than US$10 000 each) and has been an investigator for Roche Chugai, Sanofi Aventis, Celgene, Pfizer, MSD, Novartis and BMS.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.