Disparities in burden of disease in patients with rheumatoid arthritis across racial and ethnic groups.

To examine racial/ethnic differences in rheumatoid arthritis (RA) disease burden and change in clinical outcomes over time. We included CorEvitas Rheumatoid Arthritis Registry patients from two time periods (2013-2015 and 2018-2020). Clinical Disease Activity Index (CDAI) (as a continuous measure and as a dichotomous measure) and the Health Assessment Questionnaire-Disability Index (HAQ-DI) were assessed at each visit. Marginal means and their corresponding 95% confidence interval (CI) by race/ethnicity were estimated for each outcome using adjusted mixed effects linear and logistic regression models. Overall and pairwise tests were conducted to detect differences between race/ethnicity groups. Of 9,363 eligible patients (8,142 White, 527 Black, 545 Hispanic, 149 Asian), most (76%-85%) were female. At Visit 1, the mean disease duration ranged from 9.8-11.8 years. Estimated CDAI was significantly higher for Hispanics compared to Whites at Visit 1 (11.1 vs. 9.9; pairwise P = 0.033) and Visit 2 (9.2 vs. 8.0, pairwise P = 0.005). Disease activity improved over the 5-year study period among all race/ethnicity groups, though Hispanics improved less than Whites. Disease activity improved over the 5-year period across all racial/ethnicity groups, and disparities between racial/ethnicity groups in disease activity and functional status did persist over time, suggesting that further effort is needed to understand the drivers of these discrepancies to close this race/ethnicity gap. Key Points • Disease activity improved over the 5-year period across all racial and ethnic groups. • Disparities between racial and ethnic groups in disease activity and functional status did persist over time, suggesting that further effort is needed to understand the drivers of these discrepancies and close this racial gap.

Effectiveness of Tofacitinib in Patients Initiating Therapy for Psoriatic Arthritis: Results from the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.

INTRODUCTION: Randomized controlled trials have demonstrated tofacitinib efficacy for psoriatic arthritis (PsA); however, real-world effectiveness data are limited. This real-world analysis assessed baseline demographics/disease characteristics and tofacitinib effectiveness in patients with PsA in the CorEvitas PsA/Spondyloarthritis Registry. METHODS: This study (NCT05195814) included patients with PsA initiating tofacitinib from December 2017-December 2021, as monotherapy or with oral small molecules (methotrexate/leflunomide/sulfasalazine/apremilast), pre-existing use, or initiated concurrently. OUTCOMES: mean change from baseline in disease activity/patient-reported outcomes, proportion of patients achieving low disease activity (LDA)/remission at 6 ± 3 months, and discontinuation rates. RESULTS: Of 222 patients with PsA who initiated tofacitinib (60.8% as monotherapy), 123 patients had 6 ± 3 months of follow-up. At initiation, 59.7% were female, 92.3% were White, mean age was 56.3 years, PsA duration since diagnosis was 8.2 years, and 25.7% were biologic disease-modifying antirheumatic drug (bDMARD)-naïve. Improvements to 6 ± 3 months were observed with tofacitinib for Clinical Disease Activity Index for PsA (cDAPSA), DAPSA, PsA Disease Activity Score (PASDAS), Clinical Disease Activity Index, body surface area (BSA), tender/swollen joint count, patient fatigue, pain, Patient Global Skin Assessment, and Health Assessment Questionnaire-Disability Index. At 6 ± 3 months, 25.0%/7.8% of patients treated with tofacitinib achieved cDAPSA-defined LDA/remission, 18.2% achieved minimal disease activity, 30.8% had PASDAS ≤ 3.2, 42.9%/29.4% had resolved enthesitis/dactylitis, and 22.5% achieved BSA = 0%. Tofacitinib discontinuation occurred in 51.2% of patients (51.6% of monotherapy initiators) at/prior to 6 ± 3 months (27.6%/23.6%), 57.1% of whom switched to tumor necrosis factor/interleukin-17 inhibitors. Reasons for discontinuation were not reported in 85.3%/79.3% of patients who discontinued at/prior to 6 ± 3 months. CONCLUSIONS: This real-world US cohort analysis described patients with PsA newly initiating tofacitinib; most were bDMARD-experienced or receiving monotherapy treatment. In patients who remained on therapy (48.8%), tofacitinib was effective across multiple PsA domains at 6 ± 3 months. Limitations included small patient numbers at follow-up and potential selection bias. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05195814.

Effectiveness of bDMARDs in ankylosing spondylitis patients by biologic use: experience from the CorEvitas PsA/SpA Registry.

OBJECTIVE: To describe bDMARD initiators by biologic experience among ankylosing spondylitis (AS) patients and change in disease activity and patient-reported outcomes (PROs) in real-world US patients. METHODS: We included patients ≥18 years with AS based on physician diagnosis enrolled between 3/2013 and 11/2019 in the CorEvitas Psoriatic Arthritis (PSA)/Spondyloarthritis Registry (NCT02530268). Patients concurrently diagnosed with PSA were excluded. Baseline (bDMARD initiation) demographics, comorbidities, disease characteristics, treatment, and PROs were collected. Response rates and changes in disease activity and PROs between baseline and 6- and 12- month follow-up visits were calculated. RESULTS: Of the 489 AS patients in the PsA/SpA Registry, 254 AS (52.0%) patients initiated a bDMARD at enrollment or during follow-up (total initiations: AS = 313). Of the 313 AS initiations, 179 (57.2%) had a 6-month follow-up, 122 (39.0%) had a 12-month follow-up, and 94 (30.0%) had a 6- and 12-month follow-up visit. For those AS initiators with a 6-month follow-up, the mean age was 49.1 years, 44.4% were female, and 70.4%, 47.5%, 96.1%, and 46.9% had never used cDMARDs, TNFis, non-TNFis, and bDMARDs, respectively. Of these 179 AS initiators, 20.1% and 14.0% achieved ASAS20/40, respectively. Further, only 34% achieved low disease activity (ASDAS <2.1). When stratified by biologic-naivete and biologic-experience, the ASAS 20/40 achievement rates were 26.2% and 14.7%, and 21.4% and 7.4%, respectively, for this cohort. CONCLUSION: Although AS patients initiate bDMARDs, many do not achieve optimal treatment responses. Future research is needed to investigate the aspects associated with inadequate improvement and treatment response to bDMARDs.

Clinical Outcomes in Patients with Rheumatoid Arthritis After Switching Between Interleukin-6-Receptor Inhibitors and Janus Kinase Inhibitors: Findings from an Observational Study.

INTRODUCTION: This observational study evaluated response in patients with rheumatoid arthritis (RA) who switched from an interleukin-6 receptor inhibitor (IL-6Ri) to a Janus kinase inhibitor (JAKi) and vice versa. METHODS: Adult patients with RA, who initiated IL-6Ri or JAKi (following discontinuation of JAKi or IL-6Ri, respectively) during/after December 2012 and had a 6-month follow-up visit were enrolled. Clinical outcomes were evaluated at baseline and the follow-up visit. Continuous outcomes included Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire (HAQ), pain, fatigue, tender joint count, swollen joint count, Physician Global Assessment (MDGA), Patient Global Assessment (PtGA), and morning stiffness duration. Categorical outcomes included the proportion of patients achieving CDAI low disease activity (LDA), remission, and minimal clinically important differences (MCIDs) for HAQ, pain, fatigue, MDGA, and PtGA. Continuous outcomes were summarized as mean changes from baseline, and categorical outcomes as response rates. Differences in the outcome measures between groups were evaluated using linear and logistic regression models. RESULTS: Between IL-6Ri (n = 100) and JAKi initiators (n = 129), no significant differences were noted for continuous outcomes. Within both groups, a significant proportion of patients achieved LDA, remission, and MCIDs for other measures, although the odds of achieving LDA were higher among IL-6Ri (vs. JAKi) initiators with moderate-to-severe disease (adjusted odds ratio: 3.30 [1.01, 10.78]). CONCLUSIONS: Patients with RA can achieve improvement in response when switching between IL-6Ri and JAKi. Although both therapies affect the IL-6 pathway, there are distinct mechanisms of action, which likely contribute to their clinical improvement, when reciprocally switched as follow-on treatments.

A Real-World Effectiveness Study Using a Mobile Application to Evaluate Early Outcomes with Upadacitinib in Rheumatoid Arthritis.

INTRODUCTION: The impact of upadacitinib on rheumatoid arthritis (RA) symptoms was evaluated during the first 12 weeks of treatment via patient-reported outcomes (PROs) using a mobile health application (app). METHODS: Participating rheumatologists from the CorEvitas RA Registry (prospective, observational cohort) recruited patients with RA initiating upadacitinib treatment. A modified version of the ArthritisPower® app was used to collect PROs, including the Routine Assessment of Patient Index Data 3 (RAPID3), duration of morning joint stiffness, and the Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue 7a Short Form at baseline and weeks 1-4, 8, and 12. RAPID3 responses over time were assessed using Kaplan-Meier estimation to determine the proportion of patients achieving disease activity improvement and minimal clinically important difference (MCID). Results were analyzed for all patients initiating upadacitinib and a subsample of TNF inhibitor (TNFi)-experienced patients with moderate to severe disease at baseline. RESULTS: A total of 103 patients with RA initiating upadacitinib (62.1% TNFi-experienced) were included. At week 12, 53 patients (51.4%) completed the study and provided PRO data via the app. Among all patients, improvements in RAPID3, pain, morning stiffness, and fatigue were observed at week 1 and were maintained or further improved through week 12. At week 12, 37.5% of patients achieved RAPID3 low disease activity. Starting at week 1, improvements in RAPID3 disease activity category (19.4% of patients) and achievement of MCID (16.3%) were reported, with nearly 50% of patients achieving these outcomes by week 4 (RAPID3 category: 48.8%; MCID: 49.2%) and 60% by week 12 (RAPID3 category: 59.6%; MCID: 59.8%). TNFi-experienced patients generally reported similar outcomes. Patient-reported medication convenience and compliance were generally high. CONCLUSIONS: In this real-world cohort of patients with RA, treatment with upadacitinib was associated with early and significant improvement in RAPID3, pain, morning stiffness, and fatigue regardless of prior TNFi experience. Clinically meaningful improvement in RAPID3 patient-reported disease activity was observed as early as week 1, with continued improvement reported through week 12.

Comparative effectiveness of TNF inhibitor vs IL-6 receptor inhibitor as monotherapy or combination therapy with methotrexate in biologic-experienced patients with rheumatoid arthritis: An analysis from the CorEvitas RA Registry.

OBJECTIVE: Randomized controlled trials (RCTs) in biologic-naïve rheumatoid arthritis (RA) patients with high disease activity and inadequate response/intolerance to methotrexate have shown interleukin-6 (IL-6) receptor inhibitors (IL-6Ri) to be superior to tumor necrosis factor inhibitors (TNFi) as monotherapy. This observational study aimed to compare the effectiveness of TNFi vs IL-6Ri as mono- or combination therapy in biologic/targeted synthetic (b/ts) -experienced RA patients with moderate/high disease activity. METHODS: Eligible b/ts-experienced patients from the CorEvitas RA registry were categorized as TNFi and IL-6Ri initiators, with subgroups initiating as mono- or combination therapy. Mixed-effects regression models evaluated the impact of treatment on Clinical Disease Activity Index (CDAI), patient-reported outcomes, and disproportionate pain (DP). Unadjusted and covariate-adjusted effects were reported. RESULTS: Patients initiating IL-6Ri (n = 286) vs TNFi monotherapy (n = 737) were older, had a longer RA history and higher baseline CDAI, and were more likely to initiate as third-line therapy; IL-6Ri (n = 401) vs TNFi (n = 1315) combination therapy initiators had higher baseline CDAI and were more likely to initiate as third-line therapy. No significant differences were noted in the outcomes between TNFi and IL-6Ri initiators (as mono- or combination therapy). CONCLUSION: This observational study showed no significant differences in outcomes among b/ts-experienced TNFi vs IL-6Ri initiators, as either mono- or combination therapy. These findings were in contrast with the previous RCTs in biologic-naïve patients and could be explained by the differences in the patient characteristics included in this study. Further studies are needed to help understand the reasons for this discrepancy in the real-world b/ts-experienced population.

Meaningful Improvement and Worsening in Patients Who Do Not Achieve Low Disease Activity and Switch Therapy to a New Biologic or Targeted Disease-Modifying Antirheumatic Drug: Results From the CorEvitas RA Registry.

OBJECTIVE: The aim of this study was to assess the change in disease activity associated with switching from 1 biologic/targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) to another in patients with rheumatoid arthritis who did not achieve low disease activity (LDA) after 6 to 12 months of their initial treatment. METHODS: This observational study included patients from the CorEvitas Rheumatoid Arthritis Registry, who initiated a b/tsDMARD at the index visit (prebaseline), had any clinical disease activity index (CDAI) improvement but did not achieve LDA/remission at the subsequent visit (baseline), and switched therapy at baseline or between baseline and follow-up visits. Regardless of the preswitch CDAI value, 2 thresholds of CDAI change were used to define meaningful improvement and worsening for all patients: ≥6 units and ≥12 units; no meaningful change was defined as any change between -6 to +6 units and -12 to +12 units, based on respective thresholds. RESULTS: Of 1226 patients fulfilling the inclusion criteria, 93 (7.6%) switched therapy at baseline or between baseline and follow-up, after an inadequate response at the baseline visit. At follow-up, meaningful worsening occurred in 30.1% and 12.9% of switchers, whereas the remaining switchers achieved meaningful improvement (34.4% and 20.4%) or had no meaningful change (35.5% and 66.7%), based on the thresholds of ≥6 and ≥12 units, respectively. CONCLUSIONS: Rheumatoid arthritis patients, who had not achieved LDA and switched b/tsDMARD, were more likely to have meaningful improvement or no change, rather than meaningful worsening. These data may help some patients overcome their hesitancy to switch therapy, potentially improving clinical outcomes.

Socioeconomic impact of treatment with biological disease-modifying antirheumatic drugs in Japanese patients with rheumatoid arthritis.

OBJECTIVES: We evaluate the socioeconomic impact of treatment with biological and targeted synthetic disease-modifying antirheumatic drugs in Japanese patients with rheumatoid arthritis. METHODS: We analysed data retrospectively from the prospective observational CorEvitas RA Japan Registry (March 2016-February 2020). Patients were categorised into paid workers (PWs) and home workers (HWs) and further based on drug classes. We assessed medication persistence, treatment outcomes, health care resource utilisation, and socioeconomic impact over 12 months, including direct (drugs and health care resource utilisation) and indirect (loss of productivity) costs. RESULTS: Overall, 187 PWs and 114 HWs were identified. Over 12 months, medication persistence was high, treatment outcomes improved, and outpatient visits reduced in both groups. Following treatment initiation, direct costs increased, whereas indirect (loss of productivity) costs decreased in both groups. The unadjusted socioeconomic impact [Japanese yen (JPY)] increased across all drug classes in PWs (range: 29,700-151,700) and HWs (range: -28,700 to 83,000). Adjusted change in monthly socioeconomic impact was JPY 29,700-138,900 for PWs and JPY -28,000 to 92,800 for HWs. CONCLUSIONS: In this study of Japanese patients with rheumatoid arthritis, the socioeconomic burden increased across patient groups and drug classes. The decrease in indirect (loss of productivity) costs partially offset the increase in direct costs.

The effect of targeted rheumatoid arthritis therapeutics on systemic inflammation and anemia: analysis of data from the CorEvitas RA registry.

BACKGROUND: To evaluate the effects of tumor necrosis factor inhibitors (TNFi), interleukin-6 receptor inhibitors (IL-6Ri), and Janus kinase inhibitors (JAKi) on hemoglobin (Hb) and C-reactive protein (CRP) levels in adults enrolled in CorEvitas (formerly Corrona), a large US rheumatoid arthritis (RA) registry. METHODS: Patients who initiated TNFi, IL-6Ri, or JAKi treatment during or after January 2010, had Hb and CRP measurements at baseline and 6-month follow-up (± 3 months) and had continued therapy at least until that follow-up, through March 2020, were included in the analysis. Changes in Hb and CRP were assessed at month 6. Abnormal Hb was defined as < 12 g/dL (women) or < 13 g/dL (men); abnormal CRP was ≥ 0.8 mg/dL. Differences in Hb and CRP levels were evaluated using multivariable regression. RESULTS: Of 2772 patients (TNFi, 65%; IL-6Ri, 17%; JAKi, 17%) evaluated, 1044 (38%) had abnormal Hb or CRP at initiation; an additional 252 (9%) had both abnormal Hb and CRP. At month 6, the IL-6Ri group had a greater Hb increase than the TNFi (mean difference in effect on Hb: 0.28 g/dL; 95% CI 0.19-0.38) and JAKi (mean difference in effect on Hb: 0.47 g/dL; 95% CI 0.35-0.58) groups, regardless of baseline Hb status (both p < 0.001). The CRP decrease at month 6 was greater with IL-6Ri compared with TNFi and JAKi, regardless of baseline CRP status (both p < 0.05). CONCLUSION: These real-world results align with the mechanism of IL-6R inhibition and may inform treatment decisions for patients with RA.

Effectiveness of 6-month Use of Secukinumab in Patients With Psoriatic Arthritis in the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.

OBJECTIVE: To evaluate clinical and patient-reported outcomes (PROs) at 6 months after secukinumab initiation in US patients with psoriatic arthritis (PsA). METHODS: Patients with PsA in the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry who initiated secukinumab between April 1, 2017, and December 2, 2019, and maintained secukinumab at their 6-month follow-up visit were included. Achievement of minimal disease activity (MDA) among patients not in MDA at initiation; resolution (ie, no evidence) of tender and swollen joint counts, enthesitis, and dactylitis among patients with ≥ 1 of these at initiation; and change in disease activity and PROs were evaluated at 6 months in all patients and in patients who received secukinumab as a first-line biologic. RESULTS: Of the 100 eligible patients included, most (83.0%) were biologic experienced and 17.0% initiated secukinumab as a first-line biologic. At initiation, 75/90 patients (83.3%) with available data were not in MDA; 26/71 (36.6%) with follow-up data achieved MDA at 6 months. Further, 28/68 patients (41.2%) with ≥ 1 tender joint, 24/54 (44.4%) with ≥ 1 swollen joint, 17/28 (60.7%) with enthesitis, and 9/12 (75.0%) with dactylitis at initiation achieved resolution at 6 months. Improvements in clinical manifestations, PRO measures, and work productivity and activity were observed after 6 months among patients with PsA who initiated and maintained secukinumab. CONCLUSION: In this real-world population, patients with PsA who received and maintained secukinumab for 6 months achieved MDA in proportions consistent with clinical trials and demonstrated improvements in clinical manifestations and PROs.

Treatment Responses in Patients With Psoriatic Arthritis Axial Disease According to Human Leukocyte Antigen-B27 Status: An Analysis From the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.

OBJECTIVE: Axial disease is common and burdensome in patients with psoriatic arthritis (PsA). Human leukocyte antigen-B27 (HLA-B27) is a risk factor for axial PsA; treatment response by HLA-B27 status is inadequately characterized. This study evaluated responses to biologic disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) overall and by HLA-B27 status in patients with PsA axial disease. METHODS: This observational study included participants in the CorEvitas (formerly Corrona) PsA/Spondyloarthritis Registry who initiated bDMARD or tsDMARD treatment at baseline, had a 6-month follow-up visit, fulfilled Classification Criteria for Psoriatic Arthritis, had a baseline Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of ≥4, and had known HLA-B27 status. Disease characteristics at baseline and 6 months were evaluated overall and by HLA-B27 status. Association between HLA-B27 status and treatment response was evaluated using an analysis of covariance model. RESULTS: The analysis included 173 bDMARD or tsDMARD treatment initiations (54 [31.2%] among patients with HLA-B27+ status and 119 [68.8%] among patients with HLA-B27- status). BASDAI total and component scores decreased by ≤0.84 across groups after 6 months of bDMARD or tsDMARD therapy; these changes are not considered clinically meaningful. HLA-B27 status was not statistically significantly associated with changes in axial-related outcomes. CONCLUSION: In patients with PsA axial disease, 6 months of bDMARD or tsDMARD therapy provided only mild improvements in axial-related outcomes, irrespective of HLA-B27 status. This continued high disease activity reflects a critical unmet need for focus on the axial domain of PsA and for additional safe and effective therapies for psoriatic axial disease.

Evaluation of Clinical Diagnosis of Axial Psoriatic Arthritis (PsA) or Elevated Patient-reported Spine Pain in CorEvitas' PsA/Spondyloarthritis Registry.

OBJECTIVE: To determine the presence of axial symptoms in patients with psoriatic arthritis (PsA) and examine differences between those with or without a diagnosis of axial PsA (axPsA). METHODS: Patients with PsA at their Corevitas' (formerly Corrona) Psoriatic Arthritis/Spondyloarthritis Registry enrollment visit were stratified into 4 mutually exclusive groups based on axial manifestations: physician-diagnosed axPsA only (Dx+Sx-), patient-reported elevated spine symptoms only (Dx-Sx+; defined as Bath Ankylosing Spondylitis Disease Activity Index ≥ 4 and spine pain visual analog scale ≥ 40), physician-diagnosed and patient-reported manifestations (Dx+Sx+), and no axial manifestations (Dx-Sx-). Patient characteristics, disease activity, and patient-reported outcomes (PROs) at enrollment in each axial manifestation group were compared with the Dx-Sx- group. Associations of patient characteristics with the odds of having axial manifestations were estimated using multinomial logistic regression (reference: Dx-Sx-). RESULTS: Of 3393 patients included, 226 (6.7%) had Dx+Sx-, 698 (20.6%) had Dx-Sx+, 165 (4.9%) had Dx+Sx+, and 2304 (67.9%) had Dx-Sx-. Patients with Dx-Sx+ or Dx+Sx+ were more frequently women and had a history of depression and fibromyalgia (FM) vs patients who had Dx-Sx-. Patients with Dx+Sx- or Dx+Sx+ were more frequently HLA-B27 positive than those with Dx-Sx-. FM was significantly associated with increased odds of Dx+Sx- or Dx+Sx+. Disease activity and PROs were worse in patients with Dx-Sx+ or Dx+Sx+ than in those with Dx-Sx-. CONCLUSION: Patients who had self-reported elevated spine symptoms, with or without physician-diagnosed axPsA, had worse quality of life and higher disease activity overall than patients without axial manifestations, suggesting an unmet need in this patient population.

Durability of Response to Tocilizumab Therapy in Rheumatoid Arthritis: Data from the US-Based Corrona Rheumatoid Arthritis Registry.

INTRODUCTION: Understanding the durability of response to treatment and factors associated with failure to maintain response in a real-world setting can inform treatment decisions for patients with rheumatoid arthritis (RA). The aim of this study was to analyze durability of response to tocilizumab (TCZ) and factors associated with durability among US patients with RA in routine clinical practice. METHODS: TCZ initiators in the Corrona RA Registry were included. Durability of response was defined as maintaining continuous TCZ treatment and either an improvement of at least minimum clinically important difference (MCID) in Clinical Disease Activity Index (CDAI) score or low disease activity (LDA). Secondary analyses included patients treated with intravenous (IV) TCZ and excluded those who discontinued TCZ without reporting reasons for discontinuation. Durability was calculated with Kaplan-Meier survival analysis. Cox proportional hazards modeling identified factors associated with durability. RESULTS: Among 1789 TCZ initiators, 466, 272, and 162 were persistent (with or without durable response) with follow-up visits at 1, 2, and 3 years, respectively. Median MCID durability of response in CDAI was > 50% after 36 months overall, 26 months for TCZ-IV, and > 50% after 36 months for those with known reasons for discontinuation; longer durability was associated with increased duration of RA and higher baseline CDAI score and shorter durability with history of malignancy and history of diabetes. Median LDA durability of response was 13.0 months overall, for TCZ-IV, and for those with known reasons for discontinuation; shorter durability was associated with history of malignancy, history of diabetes, and higher baseline CDAI score. CONCLUSIONS: Median durability of response to TCZ in RA was > 3 years when defined as maintenance of MCID in CDAI score and > 1 year with the more stringent criteria of maintenance of LDA. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01402661.

Real-World Evidence to Contextualize Clinical Trial Results and Inform Regulatory Decisions: Tofacitinib Modified-Release Once-Daily vs Immediate-Release Twice-Daily for Rheumatoid Arthritis.

INTRODUCTION: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). To provide additional clinical evidence in regulatory submissions for a modified-release (MR) once-daily (QD) tofacitinib formulation, we compared real-world adherence and effectiveness between patients initiating the MR QD formulation and patients initiating an immediate-release (IR) twice-daily (BID) formulation. METHODS: Two noninterventional cohort studies were conducted. First, adherence and two effectiveness proxies were compared between patients with RA who newly initiated tofacitinib MR 11 mg QD or IR 5 mg BID in the IBM® MarketScan® Commercial and Medicare Supplemental US insurance claims databases (March 2016-October 2018). Second, using data collected in the Corrona US RA Registry (February 2016-August 2019), two Clinical Disease Activity Index (CDAI)-based measures of effectiveness were compared between tofacitinib MR 11 mg QD and IR 5 mg BID, and against noninferiority criteria derived from placebo-controlled clinical trials of the tofacitinib IR formulation. Multiple sensitivity analyses of the registry data were conducted to reassure regulators of consistent results across different assumptions. RESULTS: In each study, approximately two-thirds of patients initiated the MR formulation. In the claims database study, improved adherence and at least comparable effectiveness were observed with tofacitinib MR vs IR over 12 months, particularly in patients without prior advanced therapy. In the registry study, the noninferiority of tofacitinib MR vs IR was demonstrated for both CDAI outcomes at ~6 months; this finding was robust across multiple sensitivity analyses. CONCLUSION: These results demonstrate the value of real-world evidence from complementary data sources in understanding the impact of medication adherence with a QD formulation in clinical practice. These analyses were suitable for regulatory consideration as an important component of evidence for the comparability of tofacitinib MR 11 mg QD vs IR 5 mg BID in patients with RA. TRIAL REGISTRATION: Claims database study: ClinicalTrials.gov identifier NCT04018001, retrospectively registered July 12, 2019. Corrona US RA Registry study: ClinicalTrials.gov identifier NCT04267380, retrospectively registered February 12, 2020.

Comparative effectiveness of first-line tumour necrosis factor inhibitor versus non-tumour necrosis factor inhibitor biologics and targeted synthetic agents in patients with rheumatoid arthritis: results from a large US registry study.

OBJECTIVES: This study evaluated the comparative effectiveness of a tumour necrosis factor inhibitor (TNFi) versus a non-TNFi (biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs)) as the first-line treatment following conventional synthetic DMARDs, as well as potential modifiers of response, observed in US clinical practice. METHODS: Data were from a large US healthcare registry (Consortium of Rheumatology Researchers of North America Rheumatoid Arthritis Registry). The analysis included patients (aged ≥18 years) with a documented diagnosis of rheumatoid arthritis (RA), a valid baseline Clinical Disease Activity Index (CDAI) score of >2.8 and no prior bDMARD or tsDMARD use. Outcomes were captured at 1-year postinitiation of a TNFi (adalimumab, etanercept, certolizumab pegol, golimumab or infliximab) or a non-TNFi (abatacept, tocilizumab, rituximab, anakinra or tofacitinib) and included CDAI, 28-Joint Modified Disease Activity Score, patient-reported outcomes (including the Health Assessment Questionnaire Disability Index, EuroQol-5 Dimension score, sleep, anxiety, morning stiffness and fatigue) and rates of anaemia. Groups were propensity score-matched at baseline to account for potential confounding. RESULTS: There were no statistically significant differences observed between the TNFi and non-TNFi treatment groups for outcomes assessed, except the incidence rate ratio for anaemia, which slightly favoured the TNFi group (19.04 per 100 person-years) versus the non-TNFi group (24.01 per 100 person-years, p=0.03). No potential effect modifiers were found to be statistically significant. CONCLUSIONS: The findings of no significant differences in outcomes between first-line TNF versus first-line non-TNF groups support RA guidelines, which recommend individualised care based on clinical judgement and consideration of patient preferences.

Methotrexate Discontinuation and Dose Decreases After Therapy With Tocilizumab: Results From the Corrona Rheumatoid Arthritis Registry.

INTRODUCTION: Similar outcomes have been observed between patients with rheumatoid arthritis (RA) responding to tocilizumab (TCZ) with methotrexate (MTX) who discontinued vs. continued MTX and between patients receiving MTX who added TCZ vs. switched to TCZ monotherapy. This study examined MTX discontinuation and dose decreases in patients with RA initiating TCZ in a real-world setting. METHODS: TCZ-naïve patients enrolled in the Corrona RA registry who initiated TCZ in combination with MTX and had a 6-month follow-up visit without TCZ discontinuation were included. Patients were grouped by MTX dose at the time of TCZ initiation (≤ 10 mg, > 10 to ≤ 15 mg, > 15 to ≤ 20 mg, > 20 mg). The primary outcome was the proportion of patients with changes in MTX use at 6 months, with a secondary analysis at 12 months. Changes in disease activity [Clinical Disease Activity Index (CDAI)] and patient-reported outcomes (PROs) at 6 and 12 months were summarized descriptively. RESULTS: Of 444 included patients, 82.7% were female and 83.7% white, with mean (SD) disease duration of 11.6 (9.3) years, baseline CDAI score of 24.0 (15.4), and baseline MTX dose of 17.7 (5.8) mg. At 6 months, 139 patients (31.3%) discontinued or decreased their MTX dose. All MTX dose groups and patients who discontinued, decreased, maintained, or increased their MTX dose displayed improvements in CDAI scores and PROs at 6 months. Similar patterns and results were observed at 12 months. CONCLUSIONS: A considerable proportion of patients initiating TCZ discontinued or decreased their MTX dose after TCZ initiation. Improvements in disease activity and functionality were observed in patients who decreased or stopped MTX. This real-world study confirmed prior observations that discontinuing or decreasing MTX may be a treatment strategy for patients initiating TCZ combination therapy. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01402661.

Rheumatoid arthritis (RA) is a long-term disease that causes joint swelling, stiffness, and pain. Unless RA is treated quickly, patients can experience joint damage and disability. Patients with RA often take methotrexate (MTX) as their first treatment, but many patients do not have sufficient improvement with MTX alone. For these patients, doctors often add another medicine called a biologic to their existing treatment. However, taking more medications is associated with toxic effects and can make it harder for patients to stay on their therapy.Tocilizumab (TCZ) is a biologic that is used to treat RA. In one clinical trial, reported by Kremer et al., patients whose RA improved when they were taking TCZ plus MTX were subsequently able to stop taking MTX and their RA remained well controlled (Arthritis Rheumatol 70(8):1200­1218, 2018). However, researchers had not looked at whether patients outside of a clinical trial (in the "real world") can stop taking MTX or take less MTX after they start taking TCZ. This study used real-world data to examine if patients who start taking TCZ subsequently stop taking or take less MTX.This study showed that many patients were able to stop taking or take less MTX during the year after they started taking TCZ. Patients who stopped or decreased their MTX dose had less-active RA and reported that they felt better and had fewer symptoms. These results suggest that it is common for patients in the real world to stop taking or take less MTX after they start taking TCZ.

Effectiveness of Tocilizumab in Patients with Rheumatoid Arthritis Is Unaffected by Comorbidity Burden or Obesity: Data from a US Registry.

OBJECTIVE: Comorbidity burden and obesity may affect treatment response in patients with rheumatoid arthritis (RA). Few real-world studies have evaluated the effect of comorbidity burden or obesity on the effectiveness of tocilizumab (TCZ). This study evaluated TCZ effectiveness in treating RA patients with high versus low comorbidity burden and obesity versus nonobesity in US clinical practice. METHODS: Patients in the Corrona RA registry who initiated TCZ were stratified by low or high comorbidity burden using a modified Charlson Comorbidity Index (mCCI) and by obese or nonobese status using body mass index (BMI). Improvements in disease activity and functionality after TCZ initiation were compared for the above strata of patients at 6 and 12 months after adjusting for statistically significant differences in baseline characteristics. RESULTS: We identified patients with high (mCCI ≥ 2; n = 195) and low (mCCI < 2; n = 575) comorbidity burden and patients categorized as obese (BMI ≥ 30; n = 356) and nonobese (BMI < 30; n = 449) who were treated with TCZ. Most patients (> 95%) were biologic experienced and about one-third of patients received TCZ as monotherapy, with no significant differences between patients by comorbidity burden or obesity status. Improvement in disease activity and functionality at 6 and 12 months was similar between groups, regardless of comorbidity burden or obesity status. CONCLUSION: In this real-world analysis, TCZ was frequently used to treat patients with high comorbidity burden or obesity. Effectiveness of TCZ did not differ by comorbidity or obesity status.

Patterns of Prednisone Use in Patients with Rheumatoid Arthritis Initiating Treatment with Tocilizumab in Routine US Clinical Practice.

INTRODUCTION: Prednisone is frequently administered in combination with other therapies for the treatment of rheumatoid arthritis (RA); however, its chronic use is associated with an increased risk of comorbidities and mortality. The objective of this analysis was to evaluate changes in prednisone use among patients with RA treated with tocilizumab (TCZ) in routine US clinical practice. METHODS: TCZ-naïve patients in the Corrona RA registry who initiated TCZ were included. The primary outcome was the proportion of patients with changes in prednisone use over 12 months (primary analysis) and 6 months (secondary analysis). Changes in disease activity over 6 and 12 months (± 3 months) were assessed using the Clinical Disease Activity Index (CDAI). Outcomes were assessed in the overall population and separately for patients receiving TCZ monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs. RESULTS: Of patients receiving prednisone at baseline (mean [SD] dose: 7.7 [5.2] mg/day), 30.6% discontinued prednisone over 12 months; among patients receiving > 7.5 mg of prednisone at the time of TCZ initiation, 63.0% discontinued prednisone or decreased their dose by ≥ 5 mg over 12 months. In secondary analyses, 29.7% of patients receiving prednisone at baseline had discontinued prednisone over 6 months; among those receiving > 7.5 mg of prednisone at baseline, 51.3% discontinued or decreased their dose by ≥ 5 mg over 6 months. Changes in prednisone use and improvement from baseline in CDAI score over 6 and 12 months were comparable between patients who initiated TCZ monotherapy vs. TCZ combination therapy. CONCLUSIONS: In this real-world analysis, many patients initiating TCZ monotherapy or combination therapy were able to discontinue or decrease their prednisone dose over 12 months. Similar changes in prednisone dose were observed over 6 months. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01402661. FUNDING: Corrona, LLC and Genentech, Inc. Plain language summary available for this article.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that can lead to joint damage and disability. The steroid prednisone is a fast-acting and effective treatment for RA and is often prescribed alongside disease-modifying antirheumatic drugs (DMARDs). The health risks associated with the long-term use of prednisone have led to recommendations to minimize prednisone dose and duration of treatment. Few studies have examined the extent to which biologic DMARDs allow rheumatologists to reduce or discontinue the use of prednisone. The objective of this study was to evaluate changes in prednisone dose while receiving tocilizumab (TCZ) in patients with RA seen in routine US clinical practice. Patients who were enrolled in the Corrona RA registry and were beginning treatment with TCZ were included. Changes in prednisone use were evaluated 12 months after starting treatment. Of patients receiving prednisone at study initiation, 30.6% had discontinued prednisone over 12 months; among patients receiving > 7.5 mg of prednisone at the time of TCZ initiation, 63.0% discontinued prednisone or decreased the dose by ≥ 5 mg over 12 months. In secondary analyses, 29.7% of patients receiving prednisone at study initiation had discontinued prednisone over 6 months; among those receiving > 7.5 mg of prednisone at baseline, 51.3% discontinued or decreased the dose by ≥ 5 mg over 6 months. Changes in prednisone use and improvement in disease activity over 6 and 12 months were comparable between patients who initiated TCZ monotherapy or combination therapy with other DMARDs.

Association between cycline antibiotic and development of pseudotumor cerebri syndrome.

BACKGROUND: Cycline antibiotics (CAs) are commonly used to treat acne, blepharitis, and dry eye syndrome. Prescribers or patients may hesitate to use Cas because they may increase the risk of pseudotumor cerebri syndrome (PTCS). OBJECTIVE: We sought to assess whether CA use is associated with an increased risk of PTCS or papilledema and whether the risk depends upon dosage or duration of CA intake. METHODS: We studied patients 12 to 65 years of age who were diagnosed with acne, blepharitis, or dry eye syndrome, who were enrolled in a nationwide managed care network between January 1, 2001 and December 31, 2015, and who had no preexisting diagnosis of papilledema or PTCS. Multivariable Cox regression modeling was used to assess the risk of developing papilledema or PTCS from exposure to CAs. RESULTS: Among the 728,811 eligible enrollees (mean age, 34.7 years; 72% female), 42.0% filled ≥1 CA prescription. Of the 305,823 CA users, 170 (0.06%) were diagnosed with papilledema or PTCS. By comparison, of the 57.0% with no record of CA use, 121 (0.03%) were diagnosed with papilledema or PTCS (P < .0001). In the unadjusted model, every additional year of CA use was associated with a 70% (doxycycline: hazard ratio, 1.70 [95% confidence interval 0.98-2.97]; P = .06) or 91% (minocycline: hazard ratio, 1.91 [95% confidence interval 1.11-3.29]; P = .02) increased hazard of papilledema/PTCS relative to nonusers of CAs. After adjustment for confounders, the increased hazard of PTCS/papilledema with CA use was no longer statistically significant (P = .06, doxycycline; P = .08, minocycline). LIMITATIONS: This study relies on claims data, which lack clinical data. CONCLUSION: This study offers some evidence that CAs may increase the risk of PTCS/papilledema. However, after accounting for confounding factors in our multivariable models, we found no statistically significant association between CA use and the development of PTCS. Moreover, there was no dose-response effect whereby greater CA use was associated with a higher PTCS risk.