Overall survival in patients with rheumatoid arthritis and solid malignancies receiving biologic disease-modifying antirheumatic therapy.

INTRODUCTION/OBJECTIVES: The effects of biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) and cancer are largely unknown. We examined overall survival (OS) in patients with RA and solid malignancies receiving bDMARDs. METHODS: We performed a retrospective cohort study of patients with RA and solid malignancies seen at MD Anderson Cancer Center between 2002 and 2014. Cox proportional hazard regression models, stratified by tumor type and stage, were fit evaluating use of bDMARDs as a time fixed and time varying covariate. RESULTS: We identified 431 RA patients with solid malignancies: 111 (26%) received bDMARDs after their cancer diagnosis. Median OS from cancer diagnosis was 16.1 years. Of the patients receiving bDMARDs, most had localized disease, and only 14 (13%) had advanced cancer. In the stratified Cox models no statistically significant differences were observed between patients who received tumor necrosis factor inhibitors (TNFi) or patients who received nonTNFi, compared with those who did not receive bDMARDs (hazard ratio (HR), 0.67; 95% confidence interval (CI), 0.31, 1.44; HR, 1.10; 95% CI, 0.26, 4.60 respectively). In breast cancer patients, those receiving TNFi or nonTNFi had a numerically higher but statistically nonsignificant HR compared with those who did not receive bDMARD: HR, 1.40 (95% CI, 0.42, 4.73), and HR, 1.37 (95% CI, 0.22, 8.42) respectively. CONCLUSION: No significant differences in OS were observed between patients who received bDMARDs and those who did not. Additional data is needed to evaluate other cancer outcomes such as recurrence and progression, and patients with advanced cancer. Key Points •We found no statistically significant differences in OS between patients with RA and concomitant solid malignancies who received bDMARDs and those who did not. •Most patients who received bDMARDs had been diagnosed with early stage cancer •As few patients with advanced cancer received bDMARDs safety for this group cannot be established •No significant differences were observed between TNFi and nonTNFi, but the sample size was small.

Utilization of biologic disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis and cancer.

INTRODUCTION: Biologic disease-modifying anti-rheumatic drugs (bDMARDs) interfere with the immune system and could theoretically increase risk of malignancies. However, recent evidence has not substantiated such concerns and physicians are less reluctant in treating patients with underlying cancer with such bDMARDs. We aimed to understand the current utilization patterns of bDMARDs for the treatment of rheumatoid arthritis (RA) in cancer patients. METHODS: We performed a retrospective cohort study of patients with prevalent RA and cancer initially seen at MD Anderson Cancer Center between 2002 and 2014. A cohort of cancer patients was identified from the tumor registry, and patients with RA were identified through ICD-9 codes, followed by review of electronic medical records. We included patients 18 years and older, with a cancer diagnosis, and a diagnosis of RA by a rheumatologist. Patients were followed until 2016. RESULTS: We identified 431 patients with RA and cancer that met our inclusion criteria. Overall, 111 (26%) received bDMARDs after their cancer diagnosis; of these, 60 (54%) had received bDMARDs prior to their cancer diagnosis and continued to receive this therapy following their diagnosis. Thirteen (22%) switched to a different bDMARD, and the rest continued to receive the same agent after their cancer diagnosis. Of all patients on a bDMARD, 91 (82%) received tumor necrosis factor inhibitors (TNFi). CONCLUSIONS: The treatment landscape of patients with a history of cancer and RA is changing. Future studies evaluating the safety of bDMARDs in patients with a recent history of cancer or with active cancer are needed. Part of the data of this project was presented as a poster at the 2016 American College of Rheumatology annual meeting. Zamora NV, Siddhanamatha H, Barbo A, Tayar J, Lin H, Suarez-Almazor M. Utilization of Biologic Therapy in Patients with Rheumatoid Arthritis and Cancer [abstract].Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/utilization-of-biologic-therapy-in-patients-with-rheumatoid-arthritis-and-cancer/. Accessed September 30, 2019. Key Points • One in four patients with RA and concomitant cancer received bDMARDs, including TNFi, after their cancer diagnosis, at our institution. • Half of the patients with RA and cancer who received bDMARDs had initiated therapy prior to the cancer diagnosis, continuing thereafter.

Developing Customizable Cancer Information Extraction Modules for Pathology Reports Using CLAMP.

Natural language processing (NLP) technologies have been successfully applied to cancer research by enabling automated phenotypic information extraction from narratives in electronic health records (EHRs) such as pathology reports; however, developing customized NLP solutions requires substantial effort. To facilitate the adoption of NLP in cancer research, we have developed a set of customizable modules for extracting comprehensive types of cancer-related information in pathology reports (e.g., tumor size, tumor stage, and biomarkers), by leveraging the existing CLAMP system, which provides user-friendly interfaces for building customized NLP solutions for individual needs. Evaluation using annotated data at Vanderbilt University Medical Center showed that CLAMP-Cancer could extract diverse types of cancer information with good F-measures (0.80-0.98). We then applied CLAMP-Cancer to an information extraction task at Mayo Clinic and showed that we can quickly build a customized NLP system with comparable performance with an existing system at Mayo Clinic. CLAMP-Cancer is freely available for academic use.

A comprehensive scoping review to identify standards for the development of health information resources on the internet.

BACKGROUND: Online health information, if evidence-based and unbiased, can improve patients' and caregivers' health knowledge and assist them in disease management and health care decision-making. OBJECTIVE: To identify standards for the development of health information resources on the internet for patients. METHODS: We searched in MEDLINE, CINAHL, Scopus, Web of Science, and Google Scholar for publications describing evaluation instruments for websites providing health information. Eligible instruments were identified by three independent reviewers and disagreements resolved by consensus. Items reported were extracted and categorized into seven domains (accuracy, completeness and comprehensiveness, technical elements, design and aesthetics, usability, accessibility, and readability) that were previously thought to be a minimum requirement for websites. RESULTS: One hundred eleven articles met inclusion criteria, reporting 92 evaluation instruments (1609 items). We found 74 unique items that we grouped into the seven domains. For the accuracy domain, one item evaluated information provided in concordance with current guidelines. For completeness and comprehensiveness, 18 items described the disease with respect to various topics such as etiology or therapy, among others. For technical elements, 27 items evaluated disclosure of authorship, sponsorship, affiliation, editorial process, feedback process, privacy, and data protection. For design and aesthetics, 10 items evaluated consistent layout and relevant graphics and images. For usability, 10 items evaluated ease of navigation and functionality of internal search engines. For accessibility, five items evaluated the availability of websites to people with audiovisual disabilities. For readability, three items evaluated conversational writing style and use of a readability tool to determine the reading level of the text. CONCLUSION: We identified standards for the development of online patient health information. This proposed instrument can serve as a guideline to develop and improve how health information is presented on the internet.

Quality assessment of websites providing educational content for patients with rheumatoid arthritis.

OBJECTIVE: We performed an environmental scan of currently available websites providing educational information about rheumatoid arthritis (RA) and evaluated the quality of these websites. METHODS: We searched three separate search engines, Google, Bing, and Ask.com, on August 27, 2015, using two search terms, "arthritis" and "rheumatoid." Only patient education websites were included. Two independent investigators evaluated the accuracy, completeness, technical elements, design and esthetics, readability, usability, and accessibility of the websites. The navigation experience was also evaluated by an adult training expert. RESULTS: We identified 46 websites. Nearly all websites (98%) provided accurate information. However, no website covered all essential RA topics. Common essential topics not covered included epidemiology, pathogenesis, treatment and disease monitoring, complications, self-management, risks and benefits of treatment, prognosis, treatment adherence, questions for patients to ask their doctors, and costs. For the technical elements, all websites disclosed their ownership, but the date that the content was last updated was mentioned in only 10 websites, ranging from 2007 to 2015. The mean reading level was grade 12.1 (standard deviation ±2.3). Most websites (78%) were easy to navigate but only 33% were friendly for people with visual and/or hearing impairments. The navigation experience was rated fair or poor in 41% of the websites. CONCLUSION: Current patient information on the Internet does not comprehensively address all educational needs of patients with RA, and is often outdated. The findings from our study highlight potential areas for improvement in online education materials for patients with RA.

Methotrexate for treating rheumatoid arthritis.

BACKGROUND: Methotrexate is a folic acid antagonist widely used for the treatment of neoplastic disorders. Methotrexate inhibits the synthesis of deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and proteins by binding to dihydrofolate reductase. Currently, methotrexate is among the most commonly used drugs for the treatment of rheumatoid arthritis (RA). This is an update of the previous Cochrane systematic review published in 1997. OBJECTIVES: To evaluate short term benefits and harms of methotrexate for treating RA compared to placebo. SEARCH METHODS: The Cochrane Musculoskeletal Group Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE were searched from 1966 to 1997 and then updated to November 2013. The search was complemented with a bibliography search of the reference lists of trials retrieved from the electronic search. SELECTION CRITERIA: Randomized controlled trials and controlled clinical trials comparing methotrexate (MTX) monotherapy against placebo alone in people with RA. Any trial duration and MTX doses were included. DATA COLLECTION AND ANALYSIS: Two review authors independently determined which studies were eligible for inclusion, extracted data and assessed risk of bias. Outcomes were pooled using mean differences (MDs) for continuous variables or standardized mean differences (SMDs) when different scales were used to measure the same outcome. Pooled risk ratio (RR) was used for dichotomous variables. Fixed-effect models were used throughout, although random-effects models were used for outcomes showing heterogeneity. MAIN RESULTS: Five trials with 300 patients were included in the original version of the review. An additional two trials with 432 patients were added to the 2013 update of the review for a total of 732 participants. The trials were generally of unclear to low risk of bias with a follow-up duration ranging from 12 to 52 weeks. All trials included patients who have failed prior treatment (for example, gold therapy, D-penicillamine, azathioprine or anti-malarials); mean disease duration that ranged between 1 and 14 years with six trials reporting more than 4 years; and weekly doses that ranged between 5 mg and 25 mg. BENEFITS: Statistically significant and clinically important differences were observed for most efficacy outcomes. MTX monotherapy showed a clinically important and statistically significant improvement in the American College of Rheumatology (ACR) 50 response rate when compared with placebo at 52 weeks (RR 3.0, 95% confidence interval (CI) 1.5 to 6.0; number needed to treat (NNT) 7, 95% CI 4 to 22). Fifteen more patients out of 100 had a major improvement in the ACR 50 outcome compared to placebo (absolute treatment benefit (ATB) 15%, 95% CI 8% to 23%).Statistically significant improvement in physical function (scale of 0 to 3) was also observed in patients receiving MTX alone compared with placebo at 12 to 52 weeks (MD -0.27, 95% CI -0.39 to -0.16; odds ratio (OR) 2.8, 95% CI 0.23 to 32.2; NNT 4, 95% CI 3 to 7). Nine more patients out of 100 improved in physical function compared to placebo (ATB -9%, 95% CI -13% to -5.3%). Similarly, the proportion of patients who improved at least 20% on the Short Form-36 (SF-36) physical component was higher in the MTX-treated group compared with placebo at 52 weeks (RR 1.5, 95% CI 1.0 to 2.1; NNT 9, 95% CI 4 to 539). Twelve more patients out of 100 showed an improvement of at least 20% in the physical component of the quality of life measure compared to placebo (ATB 12%, 95% CI 1% to 24%). No clinically important or statistically significant differences were observed in the SF-36 mental component.Although no statistically significant differences were observed in radiographic scores (that is, Total Sharp score, erosion score, joint space narrowing), radiographic progression rates (measured by an increase in erosion scores of more than 3 units on a scale ranging from 0 to 448) were statistically significantly lower for patients in the MTX group compared with placebo-treated patients (RR 0.31, 95% CI 0.11 to 0.86; NNT 13, 95% CI 10 to 60). Eight more patients out of 100 showed less damage to joints measured by an increase in erosion scores compared to placebo (ATB -8%, 95% CI -16% to -1%). In the one study measuring remission, no participants in either group met the remission criteria. These are defined by at least five of (≥ 2 months): morning stiffness of < 15 minutes, no fatigue, no joint pain by history, no joint tenderness, no joint swelling, and Westergren erythrocyte sedimentation rate (ESR) of < 20 mm/hr in men and < 30 mm/hr in women. HARMS: Patients in the MTX monotherapy group were twice as likely to discontinue from the study due to adverse events compared to patients in the placebo group, at 12 to 52 weeks (16% versus 8%; RR 2.1, 95% CI 1.3 to 3.3; NNT 13, 95% CI 6 to 44). Compared to placebo, nine more people out of 100 who took MTX withdrew from the studies because of side effects (ATB 9%, 95% CI 3% to 14%). Total adverse event rates at 12 weeks were higher in the MTX monotherapy group compared to the placebo group (45% versus 15%; RR 3.0, 95% CI 1.4 to 6.4; NNT 4, 95% CI 2 to 17). Thirty more people out of 100 who took MTX compared to those who took placebo experienced any type of side effect (common or rare) (ATB 30, 95% CI 13% to 47%). No statistically significant differences were observed in the total number of serious adverse events between the MTX group and the placebo group at 27 to 52 weeks. Three people out of 100 who took MTX alone experienced rare but serious side effects compared to 2 people out of 100 who took a placebo (3% versus 2%, respectively). AUTHORS' CONCLUSIONS: Based on mainly moderate to high quality evidence, methotrexate (weekly doses ranging between 5 mg and 25 mg) showed a substantial clinical and statistically significant benefit compared to placebo in the short term treatment (12 to 52 weeks) of people with RA, although its use was associated with a 16% discontinuation rate due to adverse events.