"I couldn't carry on taking a drug like that": A qualitative study of patient perspectives on side effects from rheumatology drugs.

OBJECTIVES: There is growing interest in collecting outcome information directly from patients in clinical trials. This study evaluates what patients with rheumatic and musculoskeletal diseases (RMDs) consider important to know about symptomatic side effects they may experience from a new prescription drug. METHODS: Patients with inflammatory arthritis, who had one or more prescribed drugs for their disease for at least 12 months, participated in focus groups and individual interviews. Discussions were analysed using reflexive thematic analysis. RESULTS: We conducted seven focus groups with 34 participants across three continents. We found four overarching and two underpinning themes. The 'impact on life' was connected to participants 'daily life', 'family life', 'work life', and 'social life'. In 'psychological and physical aspects' participants described 'limitation to physical function', 'emotional dysregulation' and 'an overall mental state'. Extra tests, hospital visits and payment for medication were considered a 'time, energy and financial burden' of side effects. Participants explained important measurement issues to be 'severity', 'frequency', and 'duration'. Underpinning these issues, participants evaluated the 'benefit-harm-balance' which includes 'the cumulative burden' of having several side effects and the persistence of side effects over time. CONCLUSIONS: In treatment for RMDs, there seems to be an urgent need for feasible measures of patient-reported bother (impact on life and cumulative burden) from side effects and the benefit-harm-balance. These findings contribute new evidence in support of a target domain-an outcome that represents the patient voice evaluating the symptomatic treatment-related side effects for people with RMDs enrolled in clinical trials.

Adherence to therapy of ixekizumab and secukinumab in psoriatic arthritis patients using first- or second-line IL-17A inhibitor treatment: A Danish population-based cohort study.

OBJECTIVES: To assess the effectiveness and tolerability of first- and second-line interleukin (IL)-17A inhibitor treatment in patients with psoriatic arthritis (PsA) from 2014 to 2021, using data from the Danish Rheumatology Registry (DANBIO) by investigating adherence to therapy. METHOD: PsA patients recorded in DANBIO who received a first- or second-line IL-17A inhibitor treatment were included in this study. All patients included had previously received ≥1 TNFi treatment. Baseline characteristics were analyzed in subgroups: first-line IL-17A inhibitor treatment and second-line IL-17A inhibitor treatment. adherence to therapy of first- or second-line IL-17A inhibitor treatments were reported as Kaplan-Meier plots. RESULTS: 534 patients were included in the study; first-line switchers: 534 (secukinumab: 510, ixekizumab: 24), second-line switchers: 102 (secukinumab: 35, ixekizumab: 67). Baseline characteristics showed a similar Health Assessment questionnaire (HAQ) and Visual Analogue Scale (VAS) pain. VAS global, Disease Assessment Score-28CRP and previous number of bDMARD treatments are similar with a greater value for second-line switchers. First-line ixekizumab treated patients present a younger age, greater percentage of females, a lower disease duration and a lower CRP value. Concomitant MTX use was greater for the first-line secukinumab treated patients. First- and second-line switchers had a similar adherence to therapy. Second-line secukinumab and second-line ixekizumab switchers showed a similar adherence to treatment. CONCLUSION: PsA patients receiving first- or second-line IL-17A inhibitors showed homogeneous baseline characteristics and similar adherence to therapy. Treatment failure of the first IL-17A inhibitor treatment should not preclude a second-line IL-17A inhibitor treatment.

The impact of comorbidities on interleukin-17 inhibitor therapy in psoriatic arthritis: a Danish population-based cohort study.

Objective: To investigate the influence of comorbidities on treatment response, disease activity and persistence with first-line IL-17 inhibitor (IL-17i) treatment in patients with PsA. Methods: Patients were divided into three groups depending on the presence and/or severity of comorbidities using the Charlson Comorbidity Index (CCI). Groups were CCI 0: no comorbidities, CCI 1: one comorbidity and CCI ≥2: two or more comorbidities or one or more severe comorbidities. Outcomes in the groups were compared for treatment persistence, treatment response and disease activity. Results: A higher CCI score was associated to an elevation in baseline CRP, swollen joint count and frequency of depression and/or anxiety. The median drug persistence in the groups were CCI 0: 1.8 years, CCI 1: 1.9 years and CCI ≥2: 1.5 years, but was not statistically significant to the CCI score. There were no significant differences in clinical response rates between the groups. Conclusion: The presence of comorbidities was associated with increased baseline disease activity and frequency of depression and/or anxiety, but was not associated with shorter treatment persistence or lower clinical response rates in a cohort of 155 Danish patients with PsA treated with first-line IL-17i.

Change in psoriatic arthritis outcome measures impacts SF-36 physical and mental component scores differently: an observational cohort study.

OBJECTIVE: The objective was to investigate interplay and physical and mental component scores between change (Δ) in health-related quality of life (HRQoL) quantified by the physical component score (PCS) and mental component score (MCS) retrieved from short-form health survey (SF-36), change in disease activity (ΔDAS28CRP) and manifestations of PsA. METHODS: PsA patients initiating new medical therapy were enrolled. Independent disease measures evaluating disease activity, enthesitis, psoriasis, pain and fatigue were collected at treatment initiation and after 4 months. Interplay between independent disease measures and dependent outcome measures, ΔPCS and ΔMCS, was described with univariate regression analyses. Multivariate regression analyses were applied to assess the impact of independent variables, such as individual disease outcome measures vs ΔDAS28CRP on ΔPCS and ΔMCS. RESULTS: One hundred and eight PsA patients were included. In the univariate regression analyses, improvement in fatigue, pain and disability were associated with improvement in ΔPCS (ß; -2.08, -0.18 and -13.00, respectively; all P < 0.001) and ΔMCS (ß; -1.59, -0.12 and -6.07, respectively; P < 0.001, P < 0.001 and P = 0.003, respectively). When patient-reported outcomes were included in the final multivariate models, improvements in ΔPCS and ΔMCS were associated with improvements in pain, fatigue and disability (P < 0.001). Improvement in enthesitis impacted ΔPCS positively (ß -0.31, P < 0.001). No association was found between change in skin psoriasis, ΔPCS and ΔMCS (ß 0.15, P = 0.056 and ß 0.05, P = 0.561, respectively). CONCLUSION: In this PsA patient cohort, diminishing pain, disability and fatigue improved PCS and MCS significantly. Changes in enthesitis and psoriasis did not grossly impact HRQoL compared with DAS28CRP. Individual PsA manifestations influence HRQoL differently, which is important clinically when targeting treatment. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT02572700.

Comorbidities, pain and fatigue in psoriatic arthritis, psoriasis and healthy controls: a clinical cohort study.

OBJECTIVES: To explore the prognostic value of pre-specified comorbidities on treatment outcomes in PsA, and to compare baseline data with cutaneous psoriasis without arthritis and healthy controls (HC). METHODS: Patients initiating conventional synthetic/biological disease-modifying antirheumatic drugs were enrolled in this clinical observational cohort study, and data on comorbidities, and clinical and patient-reported outcomes were retrieved at baseline and after 4 months. Pearson's chi-squared tests were performed to investigate the prognostic value of pre-specified comorbidities and achievement of ACR20, DAPSA50 and MDA. Mann-Whitney U tests were used to compare OMERACT PsA Core Outcome Set (COS) measures at baseline and follow-up for the pre-specified comorbidities. RESULTS: A total of 100 PsA patients were included at baseline. Statistically significantly fewer patients with obesity achieved DAPSA50 compared with patients without obesity (P =0.035), and fewer patients with hypertension (P =0.034) and Charlson Comorbidity Index (CCI) ≥1 (P =0.027), respectively, achieved MDA compared with patients without these comorbidities. Patients with obesity, hypertension, widespread pain, and CCI ≥1 had significantly worse COS measures at follow-up compared with patients without these comorbidities. At baseline, patients with PsA had higher disease burden compared with patients with cutaneous psoriasis and HC, including higher pain (P <0.001) and fatigue (P <0.001) scores, and more widespread pain (P =0.002). CONCLUSION: Obesity, hypertension and CCI ≥1 were prognostic factors for poorer treatment outcome rates in PsA. Pain and fatigue were more frequently reported among patients with PsA compared with patients with cutaneous psoriasis and HC. TRIAL REGISTRATION: The Danish National Committee on Health Research Ethics: H-15009080; Data Protection Agency: 2012-58-0004; ClinicalTrials.gov: NCT02572700.

A pilot study examining patient preference and satisfaction for ava®, a reusable electronic injection device to administer certolizumab pegol.

Background: Anti-tumor necrosis factor (anti-TNF) adherence is suboptimal. ava®, a reusable electromechanical self-injection device (e-Device) developed for certolizumab pegol (CZP) administration, aims to overcome some barriers to increase adherence. This study evaluates patient experience of the e-Device and its training materials and determines patient device preference.Methods: CZP-treated patients were recruited from the Netherlands, Denmark and Sweden. Patients completed a pre-injection Assessment of Self-Injection (ASI) questionnaire investigating self-injection perception. After training, patients administered 3 consecutive self-injections using the e-Device, patient experience of each was assessed using the post-injection ASI. An additional questionnaire evaluated training materials. After Injection 3, patients indicated their preference: the e-Device or their previous device.Results: 59 patients participated; most rated the e-Device highly for satisfaction, self-confidence and ease of use. The (negative) feelings and pain and skin reactions domains had low ratings. Post-injection ASI domain scores were similar following each of the 3 e-Device injections. Training materials were rated highly (video: 8.4/10; step-by-step guide: 8.4/10). 57.1% (32/56) patients preferred the e-Device over their previous self-injection device.Conclusions: Patients were satisfied with the e-Device and most preferred it over other self-injection devices. By improving patient experience, the e-Device may help increase medication adherence.

Added value of combining methotrexate with a biological agent compared to biological monotherapy in rheumatoid arthritis patients: A systematic review and meta-analysis of randomised trials.

OBJECTIVES: To assess the efficacy and safety of methotrexate (MTX) in combination with an approved biological agent compared to biological monotherapy, in the management of patients with rheumatoid arthritis (RA). METHODS: MEDLINE, EMBASE, CENTRAL and other sources were searched for randomised trials evaluating a biological agent plus MTX versus the same biological agent in monotherapy. Co-primary outcomes were ACR50 and the number of patients who discontinued due to adverse events (AEs). Random-effects models were applied for meta-analyses with risk ratio and 95% confidence intervals and the GRADE approach was used to assess confidence in the estimates. RESULTS: The analysis comprised 16 trials (4965 patients), including all biological agents approved for RA except anakinra and certolizumab. The overall likelihood of responding to therapy (i.e. ACR50) after 6 months was 32% better when MTX was given concomitantly with biological agents (1.32 [1.20-1.45]; P < 0.001) corresponding to 11 more out of 100 patients (7-16 more); Moderate Quality Evidence. Discontinuing due to AEs from concomitant use of MTX was potentially 20% increased (1.21 [0.97-1.50]; P = 0.09) compared to biological monotherapy corresponding to 1 more out of 100 patients (0-3 more); Moderate Quality Evidence. CONCLUSIONS: Randomised trials provide Moderate Quality Evidence for a favourable benefit-harm balance supporting concomitant use of MTX rather than monotherapy when prescribing a biological agent in patients with RA although in absolute terms only 7-16 more out of 100 patients will achieve an ACR50 response after 6 months of this combination therapy.

The Parker Model: Applying a Qualitative Three-Step Approach to Optimally Utilize Input from Stakeholders When Introducing New Device Technologies in the Management of Chronic Rheumatic Diseases.

BACKGROUND AND OBJECTIVE: Qualitative methods such as semi-structured interviews and focus-groups are used to evaluate the applicability and relevance of device technologies in clinical practice, but when used alone, often lack generalizability. This study aimed to assess the face validity and feasibility of using a composite, three-step qualitative method (the Parker Model), to inform the development and implementation of ava®, an electromechanical device (e-Device) for subcutaneous self-administration of the biologic, certolizumab pegol (CZP), used to treat rheumatic diseases. METHODS: The Parker Model combines concept mapping (CM), participatory design (PD), and stakeholder evaluation (SE). CM, a structured group process, was used to identify patients' opinions and concerns regarding the e-Device. Patients used this information in iterative PD sessions to create personal e-Device prototypes in cooperation with a designer and a healthcare professional. SE was performed based on semi-structured group and individual interviews with patients and disease-management stakeholders. RESULTS: The study recruited 14 patients, two doctors, two nurses, one medical secretary, and four other public servants. Three CM workshops revealed four key considerations: technical usability, physical design, concerns, and enthusiasm. Four personalized prototypes were developed during PD sessions. SE confirmed that the identified considerations were pivotal for the implementation and adaptation of the e-Device. CONCLUSIONS: This study is the first to apply a composite, qualitative research model when introducing an e-Device for the treatment and management of rheumatic disease. Results show that input from patients and other stakeholders using the Parker Model can add value to the development and implementation of an e-Device.

Trial Characteristics as Contextual Factors When Evaluating Targeted Therapies in Patients With Psoriatic Disease: A Meta-Epidemiologic Study.

OBJECTIVE: To assess the importance of trial characteristics as contextual factors when evaluating the treatment effect of targeted therapies for patients with psoriatic disease. METHODS: We identified randomized controlled trials (RCTs) evaluating targeted therapies approved for psoriatic arthritis (PsA) and psoriasis (8 biologics and apremilast). The effect of targeted therapies was analyzed in the 2 psoriatic conditions combined by using drug retention as a common outcome, and separately by using the American College of Rheumatology 20% improvement criteria (ACR20) for PsA and the Psoriasis Area Severity Index 75% improvement score (PASI75) for psoriasis. We explored potential effect modification of trial characteristics in stratified and meta-regression analyses. Odds ratios (ORs) were calculated and compared among the trial eligibility criteria via the ratio of ORs. RESULTS: Forty-eight PsA and psoriasis trials (51 comparisons; 17,737 patients) were eligible. Overall retention was OR 2.16 (95% confidence interval [95% CI] 1.70-2.75) with higher odds for PsA trials compared with psoriasis trials (ratio of ORs 2.55 [95% CI 1.64-3.97]). The eligibility criteria "targeted therapy history," "minimum required disease duration," "required negative rheumatoid factor," and "required Classification Criteria for Psoriatic Arthritis criteria" were of importance for achieving ACR20 in PsA. The eligibility criterion "minimum required disease duration" was of importance for achieving PASI75 in psoriasis. A total of 7 PsA trials had rescue before time-point-of-retention reporting (adaptive trials). CONCLUSION: From this exploratory meta-epidemiologic study, we now have evidence from RCTs to support the notion that patients with PsA are more likely to adhere to targeted therapies compared to patients with psoriasis. Furthermore, we identified a few contextual factors of importance in regard to achieving ACR20 in PsA trials and PASI75 in psoriasis trials.

Societal costs and patients' experience of health inequities before and after diagnosis of psoriatic arthritis: a Danish cohort study.

OBJECTIVES: To comprehensively study the comorbidities, healthcare and public transfer (allowance) costs in patients with psoriatic arthritis (PsA) before and after diagnosis. METHODS: Nationwide cohort study, using data from Danish registries from January 1998 through December 2014. A total of 10 525 patients with PsA and 20 777 matched general population comparator (GPC) subjects were included. Societal costs, employment status and occurrence of comorbidities in patients with PsA both before and after diagnosis were compared with GPC subjects. RESULTS: At baseline, patients with PsA had significantly more comorbidities, including cardiovascular disease (OR 1.70 95% CI 1.55 to 1.86), respiratory diseases (OR 1.73 95% CI 1.54 to 1.96) and infectious diseases (OR 2.03 95% CI 1.69 to 2.42) compared with GPC subjects. At all time points, patients with PsA had higher total healthcare and public transfer costs; they also had lower income (p<0.001) and incurred a net average increased societal cost of €10 641 per patient-year compared with GPC subjects following diagnosis. The relative risk (RR) for being on disability pension 5 years prior to PsA diagnosis was 1.36 (95% CI 1.24 to 1.49) compared with GPC subjects. The RR increased to 1.60 (95% CI 1.49 to 1.72) at the time of diagnosis and was 2.69 (95% CI 2.40 to 3.02) 10 years after diagnosis, where 21.8% of the patients with PsA received disability pension. CONCLUSIONS: Our findings are suggestive of health inequity for patients with PsA and call for individual preventive measures and societal action.