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.

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.

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.

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.

Characteristics of Patients with Psoriasis Treated with Apremilast in the Corrona Psoriasis Registry.

INTRODUCTION: Data on the characteristics of apremilast patients in real-world settings are limited. We assessed the demographics and disease characteristics of apremilast-treated patients in the Corrona Psoriasis Registry overall and by treatment history. METHODS: The Corrona Psoriasis Registry is a large, independent, prospective, observational registry of adult patients (age ≥ 18 years) who initiate an eligible systemic medication for treatment of psoriasis at or after enrollment (incident users) or within 12 months before enrollment (prevalent users). The current analyses included psoriasis patients enrolled in the Corrona Psoriasis Registry between April 1, 2015, and January 7, 2018. Patients were adults (age ≥ 18 years) with psoriasis who were enrolled between April 1, 2015, and January 7, 2018 and initiated apremilast at the time of registry enrollment or a subsequent visit (incident users) or within the 12 months prior to registry enrollment (prevalent users). Patient characteristics were evaluated descriptively at the index date, defined as the enrollment date for prevalent users and the visit when apremilast was initiated for incident users. RESULTS: Among 660 patients who initiated apremilast at registry enrollment or a visit thereafter, psoriatic arthritis, hypertension, and hyperlipidemia were common. There were more systemic-experienced (61.4%) versus systemic-naive (38.6%) patients; 43.8% had prior biologic exposure. Most patients were not receiving concomitant systemic treatment (70.2%); 27.4% were receiving concomitant biologic therapy. Most patients had mild or moderate disease (psoriasis-involved body surface area ≤ 10% [76.0%], Investigator Global Assessment ≤ 3 [88.3%], Psoriasis Area and Severity Index ≤ 10 [84.5%]). Dermatologist-reported psoriatic arthritis was present in 47.0% of patients; 33.9% of patients had a Psoriasis Epidemiology Screening Tool score of ≥ 3, suggestive of psoriatic arthritis. Systemic-experienced apremilast patients had higher rates of obesity and comorbidities and experienced a greater impact on quality of life (mean Dermatology Life Quality Index, 7.3 vs. 6.5) versus systemic-naive patients. CONCLUSION: In this real-world observational study of apremilast users in the Corrona Psoriasis Registry, most patients had less-severe disease and higher rates of prior exposure to biologic treatments compared with patients with moderate-to-severe psoriasis enrolled in phase 3 clinical studies.

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.

Descriptive Comparisons of the Effect of Apremilast and Methotrexate Monotherapy in Oligoarticular Psoriatic Arthritis: The Corrona Psoriatic Arthritis/Spondyloarthritis Registry Results.

OBJECTIVE: Therapeutic response was evaluated among new apremilast, methotrexate (MTX), or biologic disease-modifying antirheumatic drug (bDMARD) initiators with oligoarticular psoriatic arthritis (PsA). METHODS: Patients with oligoarticular PsA in the Corrona PsA/Spondyloarthritis Registry initiating treatment with apremilast, MTX, or bDMARD, and completing 6-month follow-up were included. RESULTS: In total, 150 patients initiated monotherapy (apremilast: n = 34; MTX: n = 15; bDMARD: n = 101). Apremilast initiators had higher baseline disease activity than MTX initiators. At follow-up, apremilast initiators experienced numerically greater disease activity improvements than MTX initiators and similar improvements to bDMARD initiators. CONCLUSION: Findings suggest apremilast monotherapy is an effective option for patients with oligoarticular PsA.

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.