A quantitative comparison between the essential medicines for rheumatic diseases in children and young people in Africa and the WHO model list.

BACKGROUND: The World Health Organisation Essential Medicines List (WHO EML) guides National Essential Medicines Lists and Standard Treatment Guidelines for clearly identified disease priorities especially in low- and middle-income countries. This study compares the degree to which the basket of medicines recommended for rheumatic diseases in children and young people in National Essential Medicines Lists of countries in the WHO Africa region, corresponds to the 2021 WHO EML and WHO EML for children, as a proxy of availability. METHODS: An online search of the WHO medicines and health technology portal, the Health Ministry websites of the 54 African countries, PUBMED and Google Scholar, with search terms for 'National Essential Medicines List', AND/OR 'standard treatment guidelines' AND/OR 'Lista Nacional de Medicamentos Essenciais' AND/ OR 'Liste Nationale de Medicaments Essentiels' AND Africa AND/OR < Name of African country > was conducted. The number of medicines on the national lists were compared according to a predefined template of medicines; and the percentage similarity calculated. Descriptive statistics were derived using STATA. RESULTS: Forty-seven countries in the WHO Africa region have developed a National Essential Medicines List. Eleven countries do not have any medicines listed for rheumatic diseases. The majority of countries had less than or equal to 50% similarity with the WHO EML for rheumatic disease in children and young people, median 3 medicines (IQR 1- 4). The most common medicines on the national lists from Africa were methotrexate, sulfasalazine and azathioprine, with etanercept available in 6 countries. Seven countries had only one medicine, acetylsalicylic acid listed in the section 'Juvenile Joint diseases'. A multiple linear regression model for the predictors of the number of medicines on the national lists established that 20% of the variability was predicted by health expenditure per capita, socio-demographic index and the availability of rheumatology services (adult and/or paediatric) p = 0.006, with socio-demographic index (p = 0.035, 95% CI 0.64-16.16) and the availability of rheumatology services (p = 0.033, 95% CI 0.13 - 2.90) significant. CONCLUSION: Four countries (8.5%) in Africa have updated their National Essential Medicines Lists to reflect adequate care for children and young people with rheumatic diseases. Moving forward, efforts should focus on aligning available medicines with the WHO EML, and strengthening healthcare policy for rheumatology and pharmaceutical services, for affordable access to care and medicines.

Attitudes of patients with a rheumatic disease on drug use in the COVID-19 pandemic.

BACKGROUND: Anti-rheumatic drugs can increase the predisposition to infection, and patients may be unaware of continuing their treatment during the COVID-19 pandemic. OBJECTIVE: This study aimed to assess whether patients maintain their treatment for rheumatic conditions during the pandemic period and determine the factors responsible for discontinuation. METHODS: Patients were randomly selected from the prospectively collected database of our tertiary referral center. The patients were interviewed by telephone through a standardized closed-ended questionnaire, which is targeting the continuity of the treatment plan and the considerations related to the individual choice. The patients were asked whether they hesitated to visit the hospital for follow-up or intravenous drug administration. RESULTS: A total of 278 patients completed the questionnaire. While 62 of the patients (22.3%) had reduced or interrupted the treatment, only 11 patients (3.9%) stopped the treatment completely. A significant difference was observed between the duration of illness and the discontinuation of treatment. (p = 0.023) There was a significant difference in disease activity between the group that stopped treatment and continued treatment. (p = 0.001) There was no statistically significant difference in other demographic characteristics. One hundred thirty-five patients (48.6%) made the treatment decision by themselves, and 80% continued the treatment. Reasons for stopping the treatment were anxiety (48.4%), not being able to go to the hospital for intravenous treatment (45.1%), and not being able to find the drug (6.5%). CONCLUSION: Since patients with long-term illnesses were found to be significantly more likely to stop their treatment, this group of patients should be monitored.

Hydroxychloroquine availability during COVID-19 crisis and its effect on patient anxiety.

OBJECTIVE: To report the results of a survey exploring the experience of patients with SLE facing hydroxychloroquine (HCQ) shortage that occurred during the early phases of the COVID-19 pandemic. METHODS: A survey was designed by Lupus Europe's patient advisory network and distributed through its social media, newsflash and members' network. People with lupus were asked about their last HCQ purchases and their level of anxiety (on a 0-10 scale) with regard to not being able to have access to HCQ, once in April 2020 (first wave) and after 11 August (second wave). The results were compared. RESULTS: 2075 patients responded during the first wave; 1001 (48.2%) could get HCQ from the first place they asked, 230 (11.1%) could get the drug by going to more than one pharmacy, 498 (24.0%) obtained HCQ later from their usual pharmacy and 126 (6.1%) from other sources. 188 (9.1%) could not get any; 32 (1.5%) did not respond to this question. All countries showed significant improvement in HCQ availability during the second wave. 562 (27.4%) patients reported an extremely high level of anxiety in wave 1 and 162 (10.3%) patients in wave 2; 589 (28.7%) and 268 (17.1%) patients reported a high level of anxiety in wave 1 and wave 2, respectively. CONCLUSIONS: The HCQ shortage had a significant impact on patients with SLE and has been responsible for psychological consequences including anxiety. Indeed, despite an objective improvement in drug availability, the event is leaving significant traces in patients' mind and behaviours.

The impact of COVID-19 pandemic on rheumatology practice: a cross-sectional multinational study.

OBJECTIVE: To evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on rheumatology practice. METHOD: A cross-sectional web survey was designed by the members of the Arab League of Associations for Rheumatology (ArLAR), validated by its scientific committee and disseminated through e-mail and social media. It included close-ended questions about the impact of the pandemic on the rheumatology activities, including outpatient visits and hospitalizations (in percentage, 100% corresponds to complete suspension) and open-ended questions about unmet needs. Univariate and multivariable logistic regression analyses were used to evaluate the predictors of impact. Suggestions were developed to improve the practice. RESULTS: A total of 858 rheumatologists were included in the analysis (27.3% of registered in ArLAR), 37% were 35-44 years old, 60% were females, and 48% worked in the private sector. The impact of COVID-19 was a decrease of 69% in hospitalizations, 65% in outpatient clinic, 56% in infusion centers, and 43% in income. It was associated with the region (highest in the Gulf), use of telemedicine, impact on income and practice sector (lowest in private). There was a hydroxychloroquine shortage in 47%. Telemedicine was mostly based on traditional telephone contacts and e-mails and reimbursed in 12%. Fifteen rheumatologists (1.8%) were infected and 156 cases of COVID-19 were reported among patients. The top-cited unmet needs in rheumatology practice were access to drugs and a telemedicine platform. CONCLUSIONS: The negative impact of the COVID-19 pandemic on rheumatology practice may compromise rheumatic diseases control. Better access to drugs and providing telemedicine platforms are recommended to improve the practice. Key Points • The COVID-19 pandemic had a significant negative impact on the rheumatology practice, including access to outpatient clinic, hospitalization, and to anchor drugs. • The compromised access to rheumatology care may jeopardize the control of chronic rheumatic diseases and the long-term prognosis. • Better access to drugs and providing telemedicine platforms are strongly recommended.

Rheumatologists' practice during the Coronavirus disease 2019 (COVID-19) pandemic: a survey in Egypt.

The aim of this work is to trace how rheumatologists all over Egypt are approaching the COVID-19 pandemic and what changes it has brought about in the patients' care with special attention to its effect on vulnerable rheumatic disease (RD) patients. This survey further aims to help inform the rheumatology community about the changes in practice during the COVID-19 pandemic. The survey included 26 questions distributed to University staff members across Egypt members of the Egyptian College of Rheumatology (ECR). It takes 5-10 min to fill out. The practice setting of participating rheumatologists included University Teaching Hospitals that are the main rheumatology and clinical immunology service providers for adults and children RD patients. There was an overall agreement across the country in the responses to the survey that took a median time of 7 min to fill in. Potential changes in rheumatology outpatient practice by staff members evolved since the COVID-19 pandemic. None of the university rheumatology staff members has prescribed chloroquine or HCQ to prevent or treat COVID-19 in a non-hospitalized patient who was not previously on it. Twenty-three recommended decrease/avoid NSAIDs if the RD patient had confirmed COVID-19 or symptoms. There is an agreement to the key emerging frontline role of rheumatologists in treating COVID-19. During the pandemic, RD cases requiring admission were dealt with by several modified strategies. The overall agreement among the different university rheumatology departments during such critical situation has provoked the ECR to consider providing provisional guidelines for dealing with RD patients during this global catastrophe.

Access to high-cost medications for psoriatic arthritis in the National Health System in Brazil: the long path up to dispensation.

BACKGROUND: Pharmaceutical Assistance (PA) is a dynamic and multidisciplinary process that aims to supply health systems, programs or services with quality medicines, enabling access and health care, in an efficient and timely manner. The objective of the study was to evaluate the profile of administrative processes for the treatment of PsA, identify the time elapsed in the flow of processes and its associated factors. METHODS: A cross-sectional study of medication requests for the treatment of PsA was carried out between November 2014 and December 2016. Linear regression was used to verify the factors associated with time to delivery. RESULTS: A total of 218 cases containing 250 drugs were analyzed. The median time between the medical appointment and the first dispensation was 66 days (interquartile range, 44-90). The State proceedings, which includes requesting the drug until the authorization of treatment, was the stage that most contributed to the total time spent. The factors associated with the longer time to delivery of medications were prescriptions coming from clinics and specialty centers, from dermatologists, non-authorized processes and non-persistent patients in the treatment in 12 months. CONCLUSION: The median time to receive medicines for the PsA treatment in Belo Horizonte health region after a medical prescription was higher than 2 months. The time between the solicitation of the medicines and the authorization of the treatment in the SUS (State administrative procedure) was the main component of the total time spent.

Use of tumor necrosis factor-alpha inhibitors during pregnancy among women who delivered live born infants.

PURPOSE: To describe the use of tumor necrosis factor-alpha inhibitors (TNFis) among pregnancies ending in a live birth and with a diagnosis of ankylosing spondylitis (AS), Crohn's disease (CD), juvenile idiopathic arthritis (JIA), psoriasis (PsO), psoriatic arthritis (PsA), rheumatoid arthritis (RA), or ulcerative colitis (UC). METHODS: We identified pregnancies among women aged 15 to 54 years between 01/01/2004 and 09/30/2015 from 16 health plans participating in Sentinel. We inferred indication using ICD-9-CM codes in the 183-day period before conception. We assessed proportion of infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab by calendar year, indication, and maternal age, and compared them to proportions in an age-matched, indication-matched, and date-matched non-pregnant cohort. RESULTS: Among 19 681 pregnancies with at least one chronic inflammatory condition, 2990 (15.2%) received a TNFi. In both pregnancies and matched non-pregnant cohort, TNFi use was highest (34.4%; 55.8%) for PsA patients and lowest (6.2%; 13.4%) for PsO patients. Etanercept was most frequently used among AS/JIA/PsA/PsO/RA patients, while infliximab was the preferred TNFi for CD/UC patients. Except for infliximab and certolizumab, TNFi use during pregnancy decreased after the first trimester. Pregnancies among older pregnant women (45-54 years) were more likely to be treated compared with the matched non-pregnant cohort. CONCLUSION: There was a preference for etanercept among pregnancies with AS/JIA/PsA/PsO/RA, despite the availability of other TNFis. Decline in TNFi use after the first trimester may be related to the desire to reduce TNFis transplacental transfer and to minimize infection risk to the fetus or baby associated with live vaccine immunizations after birth.

Of patents and patent disputes - The TNFα patent files. Part 2: Enbrel, Remicade, Cimzia and Simponi.

This article is the second part of a trilogy that discusses IP issues related to anti-Tumor Necrosis factor α (TNFα) biologics. TNFα is the world's most valuable target, with accumulated sales of TNFα biologics of 34 bn USD in 2014. While in the first part of this trilogy, Humira was discussed, this second parts discusses the patent strategies of Enbrel, Remicade, Cimzia and Simponi.

Management of rheumatoid arthritis in clinical practice using treat-to-target strategy: Where do we stand in the multi-ethnic Malaysia population?

To evaluate the achievement of treat-to-target (T2T) strategy in rheumatoid arthritis (RA) and identify factors associated with failed treatment target in a public rheumatology center. A cross-sectional study was conducted from June 2015 to February 2016. RA patients with disease duration greater than 2 years and under T2T for over a year were invited to the study. Demographic, clinical data, disease activity score of 28 joints (DAS28), and clinical disease activity index (CDAI) were collected in a single routine clinic visit. Treatment target was defined as DAS28 <3.2 or CDAI ≤10. Retrospective chart review was performed to determine reasons of failed treatment target. A total of 371 patients were recruited and 87.1% were female. Mean age and duration of RA were 53.5 years (SD 10.3) and 9.1 years (SD 6.6), respectively. Ethnic distribution was 49% Chinese, 27% Malay, and 24% Indian. T2T was achieved in 81.7% of the cohort. Non-Chinese ethnicity, positive rheumatoid factor, and treatment with three disease modifying anti-rheumatic drugs (DMARDs) were associated with failed treatment target. After controlling for covariates, Malay ethnicity (OR 2.96; 95% CI 1.47-5.96) and treatment with three DMARDs (OR 2.14; 95% CI 1.06-4.35) were associated with failed treatment target. There was no association between age, gender, duration of RA, BMI, smoking status, anti-citrulinated cyclic peptide, and achievement of T2T. The most common reasons of failed treatment target were inability to escalate DMARDs due to side effects (18.8%), lack of biologics fund (15.6%), and persistent disease despite optimum treatment (14.1%). T2T was successfully implemented. Malay patients need aggressive treatment adaptation to achieve optimal outcome.

A prospective, randomized, double-blind, multicentre, parallel-group, active controlled study to compare efficacy and safety of biosimilar adalimumab (Exemptia; ZRC-3197) and adalimumab (Humira) in patients with rheumatoid arthritis.

AIM: In this study, efficacy, tolerability and safety of biosimilar adalimumab (Exemptia; Zydus Cadila) was compared with reference adalimumab (Humira; AbbVie) in patients with moderate to severe rheumatoid arthritis (RA). METHOD: In this multicentre, prospective, randomized, double-blind, active controlled parallel arm study, 120 patients with moderate to severe RA were given 40 mg of either test adalimumab (Exemptia) or reference adalimumab (Humira) by subcutaneous route every other week for 12 weeks. The primary endpoint was proportion of responders in two tretament groups by American College of Rheumatology 20 (ACR20) at week 12. The secondary endpoints were change in Disease Activity Score of 28 joints - C-reactive protein (DAS28-CRP) and proportion of patients with an ACR50 and ACR70 response in two treatment groups at week 12. Safety outcomes were also assessed. RESULTS: After 12 weeks, patients treated every other week with test adalimumab (Zydus Cadila) had statistically similar response rates as compared to reference adalimumab (AbbVie): ACR20 (82% vs. 79.2%; P > 0.7); ACR50 (46%, vs. 43.4%; P > 0.7); ACR70 (14% vs. 15.1%; P > 0.8). The change in DAS28-CRP score was -2.1 ± 1.09 and -2.1 ± 1.21, in test and reference products, respectively. It was statistically significant compared to baseline, but not significantly different between the two products. Three serious adverse events and no death was reported during the study. Both adalimumab preparations were safe and well tolerated in this study. CONCLUSION: The results demonstrated biosimilarity with respect to efficacy, tolerability and safety of test adalimumab (Exemptia) and reference adalimumab (Humira) in patients with moderate to severe RA.

Treatment of moderate rheumatoid arthritis with different strategies in a health resource-limited setting: a cost-effectiveness analysis in the era of biosimilars.

OBJECTIVES: This paper aims to explore the cost-effectiveness of reduced doses or discontinuation of etanercept biosimilar (Yisaipu) in patients with moderately active rheumatoid arthritis (RA). METHODS: A discrete event simulation model was developed to project lifetime medical costs and quality-adjusted life-years (QALYs) in moderately active RA. Strategies starting with Yisaipu 50 mg/week for nine months following Yisaipu 50 mg/week, 25 mg/week or MTX maintenance were compared. Resource consumptions related to RA were estimated from the perspective of the Chinese health care system. An endpoint of the American College of Rheumatology (ACR) response was used to estimate the utility scores. Uncertainty in model parameters was analysed by sensitivity analyses. RESULTS: When using ACR as an endpoint for determining successful treatment, strategies starting with Yisaipu 50 mg/week for nine months following Yisaipu 50 mg/week or 25 mg/week maintenance showed the greatest number of QALYs gained (nearly 11.9 and 11.3 with or without rituximab after the failure of Yisaipu, respectively). If decision makers use a threshold of 3×the per capita GDP of China or Shanghai City in 2012, then the strategies most likely to be cost-effective are initial treatment with Yisaipu 50 mg/week for nine months following MTX maintenance and Yisaipu 25 mg/week maintenance, respectively. Results were sensitive to the cost of Yisaipu. CONCLUSIONS: The analysis indicates that, in China, replacing branded etanercept with Yisaipu is likely to be a cost-effective strategy in patients with moderately active RA.

Barriers to accessing biologic treatment for rheumatoid arthritis in Greece: the unseen impact of the fiscal crisis--the Health Outcomes Patient Environment (HOPE) study.

The latest regulatory change in the distribution system of biologic disease-modifying, antirheumatic drugs limited their sale only through the designated pharmacies of the National Organization for Healthcare Services Provision (EOPYY) or the National Health System (NHS) hospitals, adding to the complexity of access to effective treatment for rheumatoid arthritis (RA) in Greece. The aim of this paper was to assess the barriers to access RA treatment, by recording patients', rheumatologists' and EOPYY pharmacists' experiences. One twenty-three patients, 12 rheumatologists and 27 pharmacists from Athens and other urban areas in Greece participated in the study. Three types of standardized questionnaires were used to elicit information from each group of respondents using the method of personal interview for patients and the method of postal survey for doctors and pharmacists. During the last year, 26% of patients encountered problems in accessing their rheumatologist and 49% of patients experienced difficulties in accessing their medication. Ninety-two percent of rheumatologists and 96% of pharmacists confirmed that patients experience difficulties in accessing RA medication. The most commonly reported reasons for reduced access to medical treatment were travel difficulties and long distance from doctor's clinic, as well as delays in booking an appointment. The most frequently reported barriers to access pharmaceutical treatment were difficulties in the prescription process, distance from EOPYY pharmacies and medicine shortages in NHS hospitals. The study showed that RA patients are facing increased barriers to access timely and effective treatment. Redesign of the current system of distribution ensuring the operation of additional points of sale is deemed necessary.

Patient's access to healthcare and treatment in rheumatoid arthritis: the views of stakeholders in Portugal.

BACKGROUND: The access to healthcare and treatment by rheumatoid arthritis (RA) patients, particularly to biologics, differs significantly among European countries.We aimed to explore the views and experiences of Portuguese healthcare stakeholders on key barriers which limit the access to treatment, and ultimately to biologics, by RA patients and to find potential solutions (leverage points) to overcome the identified barriers. METHODS: This was a qualitative research consisting of semi-structured face-to-face interviews with key stakeholders in RA framework. Thirty four individuals from eight groups of stakeholders were interviewed: rural and urban general practitioners (GPs), rheumatologists, hospital managers, hospital pharmacists, budget holders, representatives from the Portuguese Rheumatology Society and the RA Patient Association. Interviews were conducted between May and June 2011. Conventional content analysis with research triangulation was used. RESULTS: The key barriers identified were related to the accessibility to primary healthcare services, difficulties in RA diagnosis among GPs, inefficient referral to secondary healthcare and controlled process of biologics prescription in public hospitals. The leverage points identified included the improvement of epidemiological and clinical knowledge about RA in Portugal, a better understanding of the disease among patients and GPs, the clarification of biologics benefits among budget holders and a raised awareness of the current treatment guidelines. In order to further address the leverage points, the following key initiatives were proposed: optimization of RA national registry; dissemination of information on rheumatic symptoms in primary care facilities and among the general public; increase interaction between rheumatologists and GPs through clinical discussions of successfully treated patients or workshops; broader utilization of disease diagnosis and monitoring tools, such as DAS28, and implementation of hospital-based research to collect real-world data. CONCLUSIONS: Most of the key barriers limiting the access to treatment, including biologics, in RA in Portugal are upstream of rheumatology practice. Our findings suggest that future actions should be focused on the primary care level to improve referral to rheumatologists. In addition, the collection of real-world data seems essential to characterise the RA population, to improve disease management and to increase compliance with current treatment guidelines.

Patients' access to biologics in rheumatoid arthritis: a comparison between Portugal and other European countries.

BACKGROUND: Despite the widespread availability of biologics across Europe, rheumatoid arthritis (RA) patients' access to these drugs differs significantly among countries. OBJECTIVES: To compare the proportion of RA patients treated with biologics across Europe and investigate the factors that most influence it, with focus on the Portuguese case, reportedly with low access rates to biologics. METHODS: The biologics' market was characterized for 15 selected European countries. Variables potentially influencing patients' access to biologics (PAB) in RA were also collected, including demographic, disease, economic, funding and biologics' market-related data. A multivariable regression model identified the factors that best explain PAB. Based on these determinants, a cluster analysis was performed to group the countries with most similar behaviour regarding PAB allowing the evaluation of Portugal's relative position among these countries. RESULTS: The regression model (R(2) = 0.953) indicated that PAB in selected countries is explained mostly by its gross domestic product (GDP) per capita, the usage of methotrexate (MTX) and the biologics' distribution channel. Current MTX usage in Portugal shows similarity with practice from UK, France, Germany or Spain 5 years before, explaining why PAB in Portugal stood at 7% in 2010, 12 percentage points below the average of selected countries. CONCLUSIONS: Variations in RA PAB were found across selected countries with Portugal showing the lowest proportion. GDP per capita, biologics distribution channel and consumption of MTX appear to be the best explanatory factors for these fluctuations in European countries.

Sports cream and arthritic rubs: the hidden dangers of unrecognized salicylate toxicity.

I am a clinical nurse specialist in a busy family practice with many elderly patients experiencing osteoarthritis. During an evaluation for the management of long-term pain, a patient stated that he would not use a sports cream since he had heard on the news that someone had died as a result of use. What are the risks and toxicity associated with the use of these pain-relieving products?