Persistence of tumor necrosis factor inhibitor or conventional synthetic disease-modifying antirheumatic drug monotherapy or combination therapy in psoriatic arthritis in a real-world setting

This was a retrospective analysis of data from a cohort of PsA patients. The source population consisted of individuals who enrolled in the Corrona PsA/spondyloarthritis (SpA) registry. This independent, prospective, observational, disease-based registry includes adults (18 years or older) diagnosed by a rheumatologist to have PsA, axial or peripheral SpA, or ankylosing spondylitis. As of December 2017, the registry database included information on 2526 patients recruited at 35 private and academic practice sites in 22 states across the United States, with data from 10 767 patient visits and 5928 patient-years of follow-up (median, 3.3 years). Overall objectives of the registry are to understand the epidemiology and natural history of these conditions, including comorbidities, prescribing practices, and comparative effectiveness of treatments, in a real-world setting.

The Corrona PsA/SpA registry was established in accordance with the Declaration of Helsinki. All participating investigators were required to obtain full Institutional Review Board approval for conducting noninterventional research involving human subjects with a limited dataset. Sponsor approval and continuing review were obtained through a central Institutional Review Board (IRB) (New England Independent Review Board, NEIRB No. 120160070). Sponsor approval was first obtained on February 27, 2013. For academic investigative sites that did not receive a waiver to use the central IRB, full board approval was obtained from the respective governing IRBs and documentation of approval was submitted to Corrona prior to initiating any study procedures. Informed consent was obtained from all individual participants included in the study. The study is registered with http://​www.​clinicaltrials.​gov (NCT02530268).

This analysis included patients with a diagnosis of PsA who enrolled in the registry between March 21, 2013 (registry initiation), and January 31, 2017, and who received TNFi monotherapy, csDMARD monotherapy, or TNFi/csDMARD combination therapy during this period. The csDMARD category comprised methotrexate, hydroxychloroquine, leflunomide, and sulfasalazine. The TNFi category comprised therapies that were approved for the treatment of PsA before registry initiation (etanercept, adalimumab, infliximab, and golimumab). After the index date (first recorded use) for TNFi and/or csDMARD therapy, patients were required to have at least 6 months of follow-up. Thus, the entire study period was from March 21, 2013, to July 31, 2017. Of 1608 patients in the registry during the study period, 1266 had the necessary follow-up and were included in the analysis.

The Corrona PsA/SpA registry excludes patients with a diagnosis of rheumatoid arthritis, systemic lupus erythematosus, or any other form of autoimmune inflammatory arthritis as well as patients who are participating in or planning to participate in a clinical trial with a nonmarketed or marketed investigational drug (i.e., phase I–IV drug trial). This analysis did not have patient exclusion criteria beyond those of the Corrona PsA/SpA registry.

The Corrona PsA/SpA registry collects data from patients and their treating rheumatologists, including information on disease duration, prognosis, disease severity and activity, medical comorbidities, use of medications (biologics, csDMARDs, and prednisone), and adverse events. Follow-up assessments, which are completed during routine clinical encounters, are requested at least as often as every 6 months. Validated tools are used to measure the disease severity and activity. Enthesitis severity is measured with the Spondyloarthritis Research Consortium of Canada (SPARCC) scale for tenderness from 0 to 16 [10]. Dactylitis severity is measured as the number of digits with dactylitis present from 0 to 20. The percentage of body surface area affected is recorded. Nail psoriasis severity is measured on a visual analog scale from 0 to 100. Physicians measure and record tender joint count from 0 to 68, swollen joint count from 0 to 66 (excluding hips), and Disease Activity Score from 28 joints with C-reactive protein (DAS28-CRP) [11, 12]. Patients complete the Health Assessment Questionnaire modified for Spondyloarthropathies (HAQ-S) with scores from 0 (no difficulty) to 3 (unable to do) [13], global skin assessment and global joint assessment from 0 (no disease activity) to 100 (most disease activity), and a pain visual analog scale from 0 (no pain) to 100 (worst pain). Patient and physician global disease assessments are combined with 28 swollen and tender joint counts to calculate the Clinical Disease Activity Index (CDAI) from 0 to 76, where < 2.9 is remission, 2.9–10.0 low disease activity, 10.1–22.0 moderate disease activity, and > 22.0 high disease activity [14]. Disease Activity in Psoriatic Arthritis (DAPSA) scores are calculated from joint counts (68 tender/66 swollen), CRP, and patient assessments of disease activity and pain, yielding scores consistent with remission (0–4) or mild (5–14), moderate (15–28), or high (> 28) disease activity [15]. Patients use the Work Productivity and Activity Impairment questionnaire to report the effect of PsA/SpA on work (percentage of hours missed, impairment while at work, and work hours affected) and daily activities [16‐18].

For this descriptive analysis, no hypothesis was generated a priori for statistical comparisons between or across the treatment cohorts. Demographics, clinical characteristics, and disease activity at the index date were summarized by index therapy for all PsA patients in the registry who received a TNFi or csDMARD at least once during the study period and had at least 1 follow-up visit at least 6 months after the index date. Treatment patterns were summarized by index therapy for the subset of patients who completed the 12-month study visit between 9 and 15 months postindex (12 ± 3 months). Each analysis was conducted separately for two categories of treatment—“existing use” starting before registry entry or “initiated use” starting on/after registry entry.

Treatment patterns of interest based on medication use reported in the registry included treatment persistence, discontinuation, switch, and restart (Table 1). Persistence was defined as recorded use of the index therapy for at least 12 months after the index date without any treatment gap of at least 30 days. Discontinuation was defined as any treatment gap of at least 30 days without a subsequent prescription for the index therapy during follow-up. Restarting therapy was defined as a stoppage of index therapy for at least 30 days and restarting the index therapy after the treatment gap, without starting another therapy. Switching was defined as discontinuation of the index therapy and initiation of another therapy during follow-up. Patients with at least 6 months of follow-up postindex but less than 12 months of follow-up after the first use of the index therapy could not be defined as achieving treatment persistence; if they did not discontinue, switch, or restart therapy during this follow-up, they were categorized as having “no change (< 12 months).”

The following treatment patterns were also examined (Table 1): stopping therapy was defined as stopping all PsA-related drugs and not receiving any other drug therapy after a gap in therapy of at least 30 days; therapy add-on (in the TNFi monotherapy or csDMARD monotherapy cohorts) was defined as the initiation of additional medication(s) along with continuation of index medication; reduction in therapy (in the combination therapy cohort) was defined as the discontinuation of a biologic or nonbiologic and continuing TNFi monotherapy or csDMARD monotherapy; and dose stretching included patients who received a Food and Drug Administration (FDA)–approved dose of a TNFi at the index date, and less than the FDA-approved dose of that TNFi during follow-up.

At registry entry, 1144 patients with existing therapy received treatment as TNFi monotherapy (n = 421), csDMARD monotherapy (n = 347), or combination therapy (n = 376), of whom 690 were evaluable at 12 months. In the analysis of demographics and clinical characteristics by existing index therapy, the mean age at the index date was 57.7 years for csDMARD monotherapy and 51.9–53.9 years in the other groups (Table 2). Women comprised 59% of patients receiving existing TNFi monotherapy and 46–50% of patients in the other groups. Prior csDMARD use was reported for 46% of patients in the existing TNFi monotherapy group and 98–100% of patients in the other groups.

In the analysis of PsA disease activity and severity at the index date by existing index therapy, the mean scores for disability, work impairment, enthesitis, dactylitis, body surface area, and nail psoriasis were generally consistent with low disease activity, and those for CDAI and DAPSA were consistent with low or moderate disease activity (Table 2). At the index date, peripheral involvement was reported for 77–87% of patients and axial involvement for 7–14%. The mean score for DAS28-CRP was 2.8 in the TNFi monotherapy group and 3.1 in each of the other groups. The mean CDAI scores for TNFi monotherapy, csDMARD monotherapy, and combination therapy were 9.7, 11.6, and 11.7, respectively, and the mean DAPSA scores were 13.9, 17.2, and 16.5, respectively. The mean scores for disability and work impairment were low among existing therapy patients, with the mean HAQ-S scores ranging from 0.2 to 0.3 and percentage of work hours affected overall ranging from 15 to 18%. The mean duration of PsA was 10.5 years in the csDMARD monotherapy group and 13.0 years each in the TNFi monotherapy and combination therapy groups.

Of 1144 patients with existing therapy, 690 (60%) patients were evaluable for treatment patterns because they had a 12-month follow-up visit between 9 and 15 months postindex for existing TNFi monotherapy (n = 251), csDMARD monotherapy (n = 225), or combination therapy (n = 214). Most patients with existing TNFi monotherapy, csDMARD monotherapy, or combination therapy achieved either treatment persistence for at least 12 months (93, 87, and 87%, respectively) or no change in therapy with less than 12 months of follow-up after first use (6, 5, and 5%, respectively; Table 3). The postindex treatment patterns of discontinuation of index therapy, switching to another biologic, and restarting therapy after an interruption each occurred in less than 5% of patients in each group, apart from discontinuation of combination therapy in 8% of patients. TNFi dose stretching was reported for 10 (4%) patients in the TNFi monotherapy group and 3 (1%) patients in the combination therapy group.

Initiation of therapy starting on or after registry enrollment was reported for 122 patients who initiated TNFi monotherapy (n = 43), csDMARD monotherapy (n = 56), or combination therapy (n = 23), of whom 76 were evaluable at 12 months. In the analysis of demographics and clinical characteristics by initiated index therapy (Table 4), the mean age at the index date was 55.8 years for csDMARD monotherapy and 50.7–52.3 years in the other groups. Women comprised 43–48% of patients receiving initiated therapy. History of csDMARD use was reported for 30% of patients in the initiated TNFi monotherapy group, 0% in the initiated csDMARD monotherapy group, and 57% in the combination therapy group.

In the analysis of PsA disease activity and severity at the index date by initiated index therapy, the mean scores for CDAI, DAPSA, disability, work impairment, enthesitis, dactylitis, body surface area, and nail psoriasis were consistent with low or moderate disease activity (Table 4). At the index date, peripheral involvement was reported for 78–91% of patients and axial involvement for 5–13%. The mean DAS28-CRP scores for TNFi monotherapy, csDMARD monotherapy, and combination therapy were 3.4, 3.8, and 2.9, respectively. The mean CDAI scores for TNFi monotherapy, csDMARD monotherapy, and combination therapy were 12.7, 16.2, and 12.2, respectively, and the mean DAPSA scores were 19.2, 24.7, and 19.1, respectively. The mean HAQ-S scores ranged from 0.3 to 0.4, and the percentage of work hours affected overall ranged from 19 to 29%. The mean duration of PsA was 5.7 years in the csDMARD monotherapy group and 10.1–10.2 years in the other groups.

Of the 122 patients who initiated therapy, 76 (62%) were evaluable for treatment patterns because they had a 12-month follow-up visit between 9 and 15 months postindex for initiated TNFi monotherapy (n = 26), csDMARD monotherapy (n = 35), or combination therapy (n = 15). Among the patients with initiated TNFi monotherapy, csDMARD monotherapy, or combination therapy, approximately half achieved treatment persistence for at least 12 months (50, 43, and 53%, respectively), and 20% or more had no change in the index therapy during less than 12 months of follow-up after first use (27, 20, and 20%, respectively; Table 5). In the initiated TNFi monotherapy, csDMARD monotherapy, and combination therapy groups, the discontinuation of index therapy was reported for 19, 26, and 27% of patients, respectively, and switching to another biologic (or from a csDMARD to a biologic) for 4, 11, and 13% of patients, respectively; restarting therapy after an interruption of at least 30 days was not reported for any patient (Table 5). TNFi dose stretching was not reported for any patient with initiated therapy.