Prevalence and Factors Associated With Patient-Clinician Discordance Among Patients With Rheumatoid Arthritis Initiating Advanced Therapy.

OBJECTIVE: To describe and identify associated factors for patient-clinician discordance of disease assessment at biologic or Janus kinase inhibitor (JAKi) initiation and over 12 months following initiation in patients with rheumatoid arthritis (RA) from a US RA registry. METHODS: Analyses included CorEvitas RA Registry patients who initiated their first biologic or JAKi on or after February 1, 2015, and had 6- and 12-month follow-up visits. Positive discordance was defined as patient global assessment (visual analog scale [VAS-100]) minus physician's global assessment (VAS-100) equal to 30 points or more. Persistent discordance was defined as positive discordance at all three visits. Mixed-effects logistic regression was used to determine risk factors for positive discordance at initiation and for persistent discordance. RESULTS: Among 2227 first-time biologic/JAKi-initiating patients, 613 had both follow-up visits available and were included in initiation visit analyses, and of these, 163 had positive discordance at initiation and were included in persistent discordance analyses. About 30% of all patients had positive discordance at any visit, and one third of these (10% total) were persistent at all three visits. Multivariable analyses revealed that worse scores on the Clinical Disease Activity Index, greater patient-reported pain and fatigue, and greater functional impairment were associated with positive discordance at the time of therapy initiation. Being disabled versus working full-time and being female were associated with higher odds and having Medicare versus no insurance was associated with lower odds of having persistent positive discordance. CONCLUSION: Results suggest positive discordance is common among real-world patients with RA initiating their first biologic or JAKi. The identified risk factors associated with patient-clinician discordance will help clinicians foster a more patient-centric discussion in treatment decisions.

Accuracy of MRI in Assessment of High-Grade Partial Distal Biceps Tears.

BACKGROUND: Magnetic resonance imaging (MRI) is commonly used to diagnose and assess the extent of partial distal biceps injuries. The aim of this study was to report on the accuracy of MRI and the effect of injury history and study timing on its performance. METHODS: A retrospective review of all patients who underwent surgical treatment of partial thickness distal biceps tears at a single center by multiple surgeons was performed. Inclusion criteria consisted of the performance of a preoperative MRI and documentation of the intraoperatively visualized extent of the tear, and 68 patients met the criteria for inclusion. A chart review was completed to evaluate the symptom duration, injury history, and tear extent. RESULTS: All patients had distal biceps tears of greater than 50% intraoperatively. However, MRI did not indicate any tearing in 20 (29%) patients, and its sensitivity for high-grade tear was 44%. Magnetic resonance imaging was significantly less likely to be read as high-grade tears in patients with insidious onset of their symptoms in comparison with patients who reported a traumatic onset (27% vs 55%, P = .024). However, the time from symptom onset to MRI did not significantly correlate with diagnosis of a high-grade tear on MRI (r = -0.15, P = .21). CONCLUSIONS: These results indicate that MRI can underreport partial distal biceps tear extent, and this more commonly occurs in patients with insidious onset of pain.

Occult Amyloid Deposition in Older Patients Presenting With Bilateral Carpal Tunnel Syndrome or Multiple Trigger Digits.

PURPOSE: The diagnosis of amyloidosis is important for early intervention, disease monitoring, and prevention of complications and progression. Carpal tunnel syndrome (CTS) and trigger digit (TD) are two common conditions associated with early disease. The purpose of this study was to define disease prevalence among patients with bilateral CTS and multiple TDs and assess for an increased rate of diagnosis in the presence of both. METHODS: Men older than 50 years and women older than 60 years of age diagnosed with bilateral CTS, multiple TDs, or a combination of the 2 were prospectively enrolled in our study. Tenosynovial biopsy samples taken at the time of surgery were tested for the presence of amyloid using Congo red staining. Demographic and medical covariates were also collected and analyzed for differences between amyloid-positive and -negative patients. RESULTS: Fifty-six patients were enrolled in the study, and nine patients tested positive for amyloid deposition. The demographics and medical comorbidities were similar between amyloid-positive and -negative patients. Thirty patients with bilateral CTS were enrolled, and four tested positive for amyloid. For patients with multiple TDs, a total of 17 patients were enrolled, and 4 tested positive for amyloid. Among patients with multiple TDs, only men tested positive for amyloid and were, on average, younger than those who tested negative (61 and 73 years, respectively). Patients presenting with a combination of CTS and TD did not exhibit increased amyloid discovery. CONCLUSIONS: Hand surgeons should consider tenosynovial biopsy in men older than 50 years and women older than 60 years presenting with either bilateral CTS or multiple TDs. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Application of Tendon With Z-Lengthening Technique.

Tendon deficiency limits repair and reconstructive options after tendon and nerve injuries of the upper extremity. Current treatment options include intercalary tendon autograft, tendon transfers, and two-stage tenodesis, with sacrifice of the flexor digitorum superficialis. These reconstructive techniques are associated with donor site morbidity and limited in the setting of multiple tendon deficiencies. The tendon with z-lengthening (TWZL) technique is presented here as an alternative treatment method for tendon injuries and tendon transfer reconstruction after nerve injuries. The TWZL technique involves splitting a tendon longitudinally, reflecting the freed tendon limb distally, and suture augmentation at the bridge site located at the distal end of the native tendon. The TWZL technique has applications throughout the upper extremity-flexor and extensor tendons injuries, biceps and triceps tendon injuries, and tendon transfers for restoration of hand function after nerve injuries. An illustrative case example is also provided. The experienced hand surgeon should consider the TWZL technique as a potential treatment option when faced with difficult clinical conditions of the hand and upper extremities.

A Systematic Review and Meta-Analysis of Nerve Gap Repair: Comparative Effectiveness of Allografts, Autografts, and Conduits.

BACKGROUND: Ideal nerve repair involves tensionless direct repair, which may not be possible after resection. Bridging materials include nerve autograft, allograft, or conduit. This study aimed to perform a systematic literature review and meta-analysis to compare the meaningful recovery (MR) rates and postoperative complications following autograft, allograft, and conduit repairs in nerve gaps greater than 5 mm and less than 70 mm. A secondary aim was to perform a comparison of procedure costs. METHODS: The search was conducted in MEDLINE from January of 1980 to March of 2020, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were included whether they reported nerve injury type, repair type, gap length, and outcomes for MR rates. Thirty-five studies with 1559 nerve repairs were identified. RESULTS: Overall MR for sensory and motor function was not significantly different between autograft ( n = 670) and allograft ( n = 711) across both short and long gaps. However, MR rates for autograft (81.6%) and allograft (87.1%) repairs were significantly higher compared with conduits (62.2%) ( P < 0.05) in sensory short gap repairs. Complication rates were comparable for autograft and allograft but higher for conduit with regard to pain. Analysis of costs showed that total costs for allograft repair were less than autograft in the inpatient setting and were comparable in the outpatient setting. CONCLUSIONS: Literature showed comparable rates of MR between autograft and allograft, regardless of gap length or nerve type. Furthermore, the rates of MR were lower in conduit repairs. In addition, the economic analysis performed demonstrates that allograft does not represent an increased economic burden compared with autograft.

Rheumatoid Arthritis Disease Activity and Hospitalized Infection in a Large US Registry.

OBJECTIVES: The association between disease activity and infection risk among patients with rheumatoid arthritis (RA) is not clear, and it is challenging to determine because of confounding due to the effects of RA treatments and comorbidities. METHODS: Using patients with RA in the CorEvitas registry with Medicare coverage in 2006-2019, we identified eligible patients who had at least 1 visit with moderate disease activity based on the Clinical Disease Activity Index (CDAI; CDAI >10 and ≤22). Follow-up started at the subsequent CorEvitas visit. Hospitalized infection during follow-up was assessed in linked Medicare data. We calculated the incidence rate of hospitalized infection for patients in remission, and low and moderate disease activity, and estimated the effect of time-varying CDAI on hospitalized infection by controlling for baseline and time-dependent confounders using marginal structural models (MSMs). RESULTS: A total of 3,254 patients with RA were eligible for analysis, among which 529 hospitalized infections were identified during follow-up. The crude incidence of hospitalized infection was 3.8 per 100 person-years for patients in remission, 6.6 for low disease activity, and 8.0 for moderate disease activity. Using MSMs and compared with being in remission, the hazard ratio of hospitalized infection associated with low disease activity was 1.60 (95% confidence interval [95% CI] 1.13-2.28) and with moderate disease activity was 1.83 (95% CI 1.30-2.64). CONCLUSION: The risk of hospitalized infection was higher for patients with RA in low or moderate disease activity than for those in remission after accounting for the interplay of disease activity, RA treatments, treatment switching, and other potential confounders.

Primary Repair of Chronic Distal Biceps Tendon Tears.

BACKGROUND: This study reports the clinical results following primary repair of distal biceps tendon ruptures more 6 weeks after injury. METHODS: A retrospective review of distal biceps tendon repairs performed by 8 different hand surgeons from January 1, 2015 to October 15, 2020 was performed. Patients with complete tears surgically treated ≥6 weeks after injury without tendon graft were included. Thirty patients qualified and underwent chart review for complication and range of motion (ROM) data. They were contacted for final patient-reported outcome measures (PROMs) using Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) and Patient Reported Elbow Evaluation (PREE) scores. Final PROMs were obtained from 21 patients with an average follow-up of 31.3 months (range: 4-71 months). RESULTS: Average time from injury to repair was 71 days (range: 42-204). The average QuickDASH score was 6.6 (±6.2) and PREE score was 7.8 (±8.0). The amount of elbow flexion necessary to complete the repair was documented in 21 patients and averaged 64º (±10º). Postoperatively, patients achieved an average extension/flexion of 1º (±1º) to 138º (±2º) and pronation/supination of 76º (±4º) to 77º (±3º). Complications were reported in 14 patients (47%) and included 2 re-ruptures, 1 adhesive scar formation, 1 superficial infection, 1 intraoperative lateral antebrachial cutaneous nerve laceration, 12 neuropraxias, and 1 case of heterotopic ossification (HO). CONCLUSIONS: Primary repair of chronic distal biceps tendon tears greater than 6 weeks from injury demonstrated excellent PROMs and elbow ROM. However, the complication rate may be higher than early repair.

Predicting Response to Tocilizumab Monotherapy in Rheumatoid Arthritis: A Real-world Data Analysis Using Machine Learning.

OBJECTIVE: Tocilizumab (TCZ) has shown similar efficacy when used as monotherapy as in combination with other treatments for rheumatoid arthritis (RA) in randomized controlled trials (RCTs). We derived a remission prediction score for TCZ monotherapy (TCZm) using RCT data and performed an external validation of the prediction score using real-world data (RWD). METHODS: We identified patients in the Corrona RA registry who used TCZm (n = 452), and matched the design and patients from 4 RCTs used in previous work (n = 853). Patients were followed to determine remission status at 24 weeks. We compared the performance of remission prediction models in RWD, first based on variables determined in our prior work in RCTs, and then using an extended variable set, comparing logistic regression and random forest models. We included patients on other biologic disease-modifying antirheumatic drug monotherapies (bDMARDm) to improve prediction. RESULTS: The fraction of patients observed reaching remission on TCZm by their follow-up visit was 12% (n = 53) in RWD vs 15% (n = 127) in RCTs. Discrimination was good in RWD for the risk score developed in RCTs, with area under the receiver-operating characteristic curve (AUROC) of 0.69 (95% CI 0.62-0.75). Fitting the same logistic regression model to all bDMARDm patients in the RWD improved the AUROC on held-out TCZm patients to 0.72 (95% CI 0.63-0.81). Extending the variable set and adding regularization further increased it to 0.76 (95% CI 0.67-0.84). CONCLUSION: The remission prediction scores, derived in RCTs, discriminated patients in RWD about as well as in RCTs. Discrimination was further improved by retraining models on RWD.

Evidence-Based Approach to Timing of Nerve Surgery: A Review.

ABSTRACT: Events causing acute stress to the health care system, such as the COVID-19 pandemic, place clinical decisions under increased scrutiny. The priority and timing of surgical procedures are critically evaluated under these conditions, yet the optimal timing of procedures is a key consideration in any clinical setting. There is currently no single article consolidating a large body of current evidence on timing of nerve surgery. MEDLINE and EMBASE databases were systematically reviewed for clinical data on nerve repair and reconstruction to define the current understanding of timing and other factors affecting outcomes. Special attention was given to sensory, mixed/motor, nerve compression syndromes, and nerve pain. The data presented in this review may assist surgeons in making sound, evidence-based clinical decisions regarding timing of nerve surgery.

Postapproval Comparative Safety Study of Tofacitinib and Biological Disease-Modifying Antirheumatic Drugs: 5-Year Results from a United States-Based Rheumatoid Arthritis Registry.

OBJECTIVE: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We compared 5-year adverse event (AE) incidence rates (IRs) between patients initiating tofacitinib and those initiating new biological disease-modifying antirheumatic drugs (bDMARDs) within the United States (US) Corrona RA registry. METHODS: IRs (number of first events/100 patient-years) of major adverse cardiovascular events (MACE), serious infection events (SIEs), herpes zoster (HZ), malignancies, and death were estimated among tofacitinib and bDMARD initiators, regardless of dose/schedule, between November 6, 2012 (US Food and Drug Administration tofacitinib approval), and July 31, 2018 (follow-up through January 31, 2019). Propensity score (PS) methods were used to control for nonrandom prescribing practices. Hazard ratios (HRs) were calculated to compare rates using multivariable-adjusted Cox regression. Different risk windows were used for acute (MACE, SIEs, HZ, and venous thromboembolic events [VTEs]) and long-term (malignancy and death) events. VTEs were assessed descriptively. RESULTS: For MACE, SIEs, and HZ, 1999 (3152.1 patient-years) and 8358 (12 869.4 years) tofacitinib and bDMARD initiators were included, respectively; for malignancy/death, 1999 (4505.6 patient-years) and 6354 (16 670.8 patient-years) initiators were included, respectively. AE rates were similar across cohorts, except for HZ, which was significantly higher with tofacitinib versus bDMARDs (PS-trimmed adjusted HR 2.32; 95% confidence interval [CI] 1.43-3.75). There were 45 (zero serious) and 88 (five serious) HZ events with tofacitinib and bDMARDs, respectively. Sensitivity analyses demonstrated similar results. VTE IRs (95% CI) were 0.29 (0.13-0.54) and 0.33 (0.24-0.45) for tofacitinib and bDMARDs, respectively. CONCLUSION: In this registry analysis, both cohorts had similar MACE, SIE, malignancy, death, and VTE rates; HZ rates were higher for tofacitinib initaitors than for bDMARD initiators.

Pseudoaneurysm of the Radial Artery After CMC Arthroplasty.

Pseudoaneurysm of the radial artery is an unusual condition. Most radial artery pseudoaneurysms occur as a result of catheterization; however, any traumatic event that damages the vessel can lead to a symptomatic pseudoaneurysm. This report presents a case of an unusual late presentation of clinical symptoms associated with a pseudoaneurysm of the radial artery after arthroplasty of the thumb carpometacarpal joint.

The Clinical Disease Activity Index and the Routine Assessment of Patient Index Data 3 for Achievement of Treatment Strategies.

OBJECTIVE: To compare the Clinical Disease Activity Index (CDAI) with the Routine Assessment of Patient Index Data 3 (RAPID3) from 2 large United States registries. METHODS: Using a cross section of clinic visits within 2 registries, we determined whether the outcome of each metric would place the patient in remission (REM), low (LDA), moderate (MDA), or high disease activity (HDA) using the CDAI, with the assumption that a patient in MDA or HDA would be a candidate for acceleration of treatment. RESULTS: We identified significant disparities between the 2 indices in final disease categorization using each index system. For patients identified in LDA by CDAI, RAPID3 identified 20.4% and 28.3% as LDA in Corrona and the Brigham and Women's Rheumatoid Arthritis Sequential Study (BRASS), respectively. For patients identified as MDA by CDAI, RAPID3 identified 36.2% and 31.1% as MDA in Corrona and BRASS, respectively, with the greatest disparities within each system identified for LDA and MDA activity by the CDAI (20.4% and 36.2% agreement of RAPID3 with CDAI, respectively, in Corrona and 28.3% and 31.1% agreement in BRASS). Overall comparison between CDAI and RAPID3 in the 4 disease categories resulted in estimated κ = 0.285 in both. The RAPID3 scores indicated the potential for treat-to-target acceleration in 34.4% of patients in REM or LDA based on CDAI in Corrona and 27.7% in BRASS, respectively. CONCLUSION: The RAPID3, based on patient-reported outcomes, shows differences with CDAI categories of disease activity. The components of CDAI are not highly correlated with RAPID3, except for patient global assessment. These differences could significantly affect the decision to advance treatment when using a treat-to-target regimen.

Evaluation of Changes in Skin and Joint Outcomes and Associated Treatment Changes in Psoriatic Arthritis (PsA): Experience From the Corrona PsA/SpA Registry.

OBJECTIVE: To characterize skin severity and joint activity outcomes and associated treatment changes in patients with psoriatic arthritis (PsA) through 12 months of follow-up after enrollment in the Corrona Psoriatic Arthritis/Spondyloarthritis (PsA/SpA) Registry. METHODS: Patients ≥ 18 years of age with a diagnosis of PsA and a history of psoriasis between March 21, 2013, and September 30, 2016, were enrolled (n = 647). Demographics, clinical features, and treatment characteristics were collected and stratified by skin severity and joint activity. Change in joint and skin from enrollment to the 12-month visit was classified by change in category of Clinical Disease Activity Index (CDAI) or body surface area (BSA). Tests of association evaluated the relationship between changes in therapy and changes in skin severity and joint activity. RESULTS: Patients with improvement in both joint activity and skin severity saw the largest median reduction in both CDAI and BSA, while those who worsened in both had the greatest median increase in both CDAI and BSA. The majority of PsA patients (> 50%) had no change in skin severity regardless if they had reduced therapy (50%), no therapy changes (54%), or increased therapy (56%; P = 0.5875). However, there was a significant association between changes in therapy and changes in joint activity (P < 0.001). Patients who increased therapy were more likely to have improvement in joint activity (32%) compared to patients who reduced therapy (22%) or had no therapy changes (11%). CONCLUSION: The clinical implication for our findings suggests the assessment and incorporation of both skin and joint components may be advisable.

Real-World Outcomes Associated With Methotrexate, Sulfasalazine, and Hydroxychloroquine Triple Therapy Versus Tumor Necrosis Factor Inhibitor/Methotrexate Combination Therapy in Patients With Rheumatoid Arthritis.

OBJECTIVE: Though randomized controlled trials have demonstrated relatively comparable clinical outcomes with triple therapy (methotrexate [MTX], sulfasalazine [SSZ], and hydroxychloroquine [HCQ]) compared to combination therapy (tumor necrosis factor inhibitor [TNFi] and MTX), real-world experiences comparing these strategies have not been well studied. METHODS: We evaluated the clinical effectiveness and effects of medication discontinuation of triple therapy with MTX/SSZ/HCQ versus combination therapy with TNFi/MTX in rheumatoid arthritis (RA) patients enrolled in the Corrona RA Drug Safety & Effectiveness Registry. Propensity score matching was used to match patients up to a ratio of 1:3 to adjust for imbalances between treatment groups, with stratification performed according to biologics-naive or biologics-exposed status of study participants. RESULTS: Patients eligible for analysis in this study included biologics-naive RA patients (3,926 who received combination therapy with TNFi/MTX and 262 who received triple therapy with MTX/SSZ/HCQ) and biologics-exposed RA patients (3,365 who received combination therapy with TNFi/MTX and 130 patients who received triple therapy with MTX/SSZ/HCQ). Before propensity score matching, numerous factors were imbalanced between the treatment groups, with triple therapy patients generally being older, having a longer disease duration of RA and lower RA disease activity, and more likely having a history of malignancy and other comorbidities. After matching, almost all (93-98%) triple therapy patients could be matched to TNFi/MTX therapy patients, and cohort characteristics were generally well balanced. Discontinuation of medication was greater in triple therapy patients referent to TNFi/MTX therapy patients (adjusted hazard ratio [HR] of 2.17 [95% confidence interval 1.63-2.88] in the biologics-naive group; adjusted HR of 1.51 [95% confidence interval 1.06-2.15] in the biologics-exposed group). At 6 months, the proportion of biologics-naive patients attaining low disease activity was significantly greater in the TNFi/MTX treatment group (49.2% in TNFi/MTX therapy patients versus 33.3% in triple therapy patients), as was the mean change in Clinical Disease Activity Index scores (-9.3 units versus -5.5 [95% confidence interval -1.5, -6.1]). Corresponding results in the biologics-exposed patients numerically favored TNFi/MTX therapy compared to triple therapy but did not reach statistical significance. CONCLUSION: Few patients receive triple therapy with MTX/SSZ/HCQ in the US. In the present study, drug persistence and clinical effectiveness outcomes were less favorable in triple therapy patients compared to TNFi/MTX therapy patients.

Efficacy of a single, image-guided corticosteroid injection for glenohumeral arthritis.

BACKGROUND: Limited data are available on the efficacy of cortisone injections for glenohumeral osteoarthritis (GHOA). The amount and longevity of pain relief provided by a single cortisone injection are unclear. Additionally, it remains uncertain how the severity of radiographic GHOA and patient-reported function and pain levels impact the efficacy of an injection. Therefore, we sought to describe the relief provided by a single, image-guided glenohumeral injection in patients with GHOA. We hypothesized that patients with more severe radiographic GHOA and poorer baseline shoulder function would require earlier secondary intervention. METHODS: Patients with symptomatic GHOA who elected to receive a corticosteroid injection for pain relief were prospectively enrolled. A phone interview was conducted to record the baseline Oxford Shoulder Score (OSS) and visual analog scale (VAS) score prior to the injection, as well as the OSS and VAS score at months 1, 2, 3, 4, 6, 9, and 12 after the injection. The endpoint of the study occurred when patients required a second injection, progressed to surgery, or reached month 12. Patients were grouped by their respective baseline OSS (mild vs. moderate or severe) and Samilson-Prieto radiographic classification (mild, moderate, or severe) for analysis. RESULTS: We analyzed 30 shoulders (29 patients). Of the patients, 52% were men. The average age was 66.1 years. No significant difference in overall survival (defined as no additional intervention) was seen between groups based on either the OSS or Samilson-Prieto grade. Additionally, the OSS and VAS score at each follow-up were compared with baseline values. For the entire cohort, a clinically significant difference was seen between baseline and months 1-4 for the OSS and between baseline and months 1-4, 6, 9, and 12 for the VAS score. DISCUSSION: This study aimed to determine the efficacy of corticosteroid injections for GHOA. There were no differences in the need for secondary intervention in this population based on the severity of either the OSS or the Samilson-Prieto radiographic classification. However, patients with more severe shoulder dysfunction based on the OSS did experience statistically significantly greater symptomatic relief than patients with milder dysfunction. Additionally, following a single injection, patients in this cohort experienced statistically and clinically relevant improvements in shoulder function and pain up to 4 months after injection.

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.

Hydroxychloroquine and the risk of respiratory infections among RA patients.

OBJECTIVES: To determine the effect of hydroxychloroquine on the incidence of new respiratory infections in a large registry of rheumatoid arthritis (RA) patients compared with a matched cohort receiving other conventional disease-modifying antirheumatic drugs (csDMARDs). METHODS: We reviewed physician-reported infections including upper respiratory infections (URI), bronchitis and pneumonia in the Corrona RA registry from June 2008 to February 2020 with the goal of comparing infections in biologic/targeted synthetic (b/ts) DMARDs naive HCQ starts compared with starts of other csDMARDs and no HCQ. Patients on different interventions were compared using time-varying adjusted Cox models adjusting for age, sex, duration of RA, BMI, disease activity, smoking status, concurrent medications, season of the year, year of onset and history of serious infections, diabetes or cardiovascular disease (CVD). A secondary analysis in a set of propensity-matched starts were also compared adjusting for time-varying covariates. The analysis was repeated including URI and bronchitis only and also for serious respiratory infections only. RESULTS: No evidence of differences was found in the incidence of any respiratory infection (URI, bronchitis, pneumonia) in patients receiving HCQ compared with other csDMARDs: HR=0.87 (0.70 to1.07) in adjusted analyses and HR=0.90 (0.70 to 1.17) in adjusted matched analysis. Similar results were found in the analysis of URI and bronchitis only and for serious respiratory infections only. CONCLUSIONS: In patients with RA, the risk for respiratory infections was similar among patients using HCQ as compared to other non-biologic DMARDs.