Miklos Szolics

Biosimilars: opinion of an expert panel in the Middle East

ABSTRACT Background: Several biotechnology-derived drugs are reaching the end of their patent lives. As a result, so-called biosimilar products are in development, and a few have already gained approval in Europe and other countries such as the USA. Biosimilars, unlike generic versions of conventional drugs, are not identical to their reference product, and their production is complex and sensitive to even slight changes in the manufacturing and storage process. Therefore, the registration of these products requires more stringent evaluation than that for conventional generics. Methods and scope: A consensus group of experts from the Near and Middle East discussed the currently available guidelines for registration of biosimilars – including those produced by the European Medicines Agency (EMEA) – and their application in this region. To inform this report, a literature search was also conducted on PubMed in January 2008, using the search terms ‘biosimilar’ and ‘follow-on biologic’. This paper provides an overview of the issues in the development and registration of biosimilars, a description of the EMEA guidelines and the recommendations of the consensus group for the registration of biosimilars in the Middle East. Findings: Because of the complex nature of biosimilars and their potential immunogenicity, these products cannot undergo the abbreviated approval process used for generic agents. Instead demonstration of their quality, safety and efficacy, in comparison with their reference biological product, is required. Conclusions: The consensus group recommended the implementation of the EMEA guidelines as the basis of Regional guidelines for the registration of biosimilars in the Near and Middle East. Registration would, therefore, require demonstration of the robustness of the manufacturing process and quality-control methods, the comparability of pharmacokinetics, pharmacodynamics, efficacy and safety between the biosimilar and reference product and plans for post-marketing surveillance of the long-term risks and immunogenicity of new biosimilars.

Adherence to disease-modifying drugs in patients with multiple sclerosis: a consensus statement from the Middle East MS Advisory Group.

ABSTRACT Adherence to therapy is a key issue in chronic illnesses. In addition, several features of multiple sclerosis (MS) and its treatment may increase the likelihood of patient nonadherence and discontinuation of treatment. Nonadherence will obviously compromise the efficacy of disease-modifying drugs in patients with MS. This subject was discussed by a group of local MS specialists from the Middle East. The group debated several key questions about the features and causes of patient nonadherence and its management. Further, they made recommendations for optimizing treatment adherence in this area.

Will New Injection Devices for Interferon Beta-1a s.c. Affect Treatment Adherence in Patients With Multiple Sclerosis? An Expert Opinion in the Middle East

ABSTRACT Treatment adherence to disease modifying drugs (DMDs) in multiple sclerosis is sub-optimal. This, in turn, can affect patients’ long-term responses to therapy. A key factor that influences treatment adherence is the need for self-injection of DMDs, which can be demanding and disruptive for patients, and difficult for those with cognitive difficulties or reduced manual dexterity. In addition, pain resulting from poor injection technique, and needle anxiety, may both compromise adherence. Changes to the formulation of interferon (IFN) beta-1a for subcutaneous injection that were designed to improve injection local tolerability, and changes in drug-delivery technology, designed to make injections simpler and more convenient for patients, were reviewed by a group of experts on MS in the Middle East. The group also considered the possible effects of these changes in drug delivery technology on patient adherence to IFN beta-1a s.c.

Future of Management of Multiple Sclerosis in the Middle East: A Consensus View from Specialists in Ten Countries

The prevalence of multiple sclerosis (MS) is now considered to be medium-to-high in the Middle East and is rising, particularly among women. While the characteristics of the disease and the response of patients to disease-modifying therapies are generally comparable between the Middle East and other areas, significant barriers to achieving optimal care for MS exist in these developing nations. A group of physicians involved in the management of MS in ten Middle Eastern countries met to consider the future of MS care in the region, using a structured process to reach a consensus. Six key priorities were identified: early diagnosis and management of MS, the provision of multidisciplinary MS centres, patient engagement and better communication with stakeholders, regulatory body education and reimbursement, a commitment to research, and more therapy options with better benefit-to-risk ratios. The experts distilled these priorities into a single vision statement: “Optimization of patient-centred multidisciplinary strategies to improve the quality of life of people with MS.” These core principles will contribute to the development of a broader consensus on the future of care for MS in the Middle East.

How global MS prevalence is changing: A retrospective chart review in the United Arab Emirates

BACKGROUND Multiple Sclerosis (MS) is an autoimmune disorder leading to central nervous system inflammation. Traditionally, reported MS prevalence rates in the Middle East are low. Few studies include age/sex standardization giving an unreliable estimate of regional prevalence. OBJECTIVE to determine the prevalence, incidence and characteristics of MS in Abu Dhabi, United Arab Emirates. METHODS A retrospective chart review was conducted at the four largest hospitals in Abu Dhabi Emirate between 2010 and 2014. Data collected included MS type, age and symptoms at onset, expanded disability status scale, treatment, laboratory findings and family history. RESULTS 510 patients were identified consisting of 318 (62.2%) Emiratis and 192 (37.6%) expatriates. Total crude prevalence rate was 18/100,000 (95% CI: 10-30/100,000). Crude prevalence rate in Emiratis was 57.09 (95% CI:50 to 63/100,000) but increased to 64.44 (95% CI: 57 to 72/100,000) when age standardized. Age-standardized incidence rate in Emiratis was 6.0 MS cases per 100,000 person-years (95% CI: 5.5 to 6.5 cases per 100,000 person-years). CONCLUSION At 64.44/100,000, the Abu Dhabi Emirati population has one of the highest, most reliable prevalence rate on the Arab peninsula. Age/sex standardized prevalence rates, uncommonly reported in the Middle East, should be standard for all prevalence studies.

Novel PNKP mutation in siblings with ataxia-oculomotor apraxia type 4

Abstract The phenotypic and genetic spectrum of ataxia with oculomotor apraxia (AOA) disorders is rapidly evolving and new technologies such as genetic mapping using whole exome sequencing reveal subtle distinctions among the various subtypes. We report a novel PNKP mutation in two siblings with progressive ataxia, abnormal saccades, sensorimotor neuropathy and dystonia consistent with the AOA type 4 phenotype. Laboratory evaluation revealed hypoalbuminemia, hypercholesterolemia with elevated LDL, elevated IgE levels and normal α fetoprotein levels. Eye movement examination demonstrated a marked saccade initiation defect with profound hypometric horizontal saccades. Vertical saccades were also affected but less so. Also present were conspicuous thrusting head movements when attempting to change gaze, but rather than an apraxia these were an adaptive strategy to take advantage of an intact vestibulo-ocular reflex to carry the eyes to a new target of interest. This is demonstrated in accompanying videos.

Novel mutation in the KCNJ10 gene in three siblings with seizures, ataxia and no electrolyte abnormalities

Abstract We report a consanguineous family with three affected siblings with novel mutation in the KCNJ10 gene. All three presented with central nervous system symptoms in the form of infantile focal seizures, ataxia, slurred speech with early developmental delay and intellectual disability in two siblings. None had any associated electrolyte abnormalities and no symptomatic hearing deficits were observed.

Pediatric Multiple Sclerosis in the United Arab Emirates: Characteristics From a Multicenter Study and Global Comparison:

We delineate the clinical characteristics, incidence, and prevalence of pediatric-onset multiple sclerosis in Abu Dhabi, United Arab Emirates, from 2010 to 2014. Eighty-two patients (65% female) were identified. Fifty-three (64.6%) were Emiratis (45 from Abu Dhabi and 8 from 5 other emirates) and 29 were expatriates. Mean age of onset was 15.9 years overall, 15.3 years in males and 16.3 years in females. Patients with onset before age 12 years presented with visual symptoms while those with onset after age 12 years presented with a mixture of visual, motor and sensory symptoms. Interferon beta-1a was the most frequently used disease-modifying therapy (48%). In Abu Dhabi Emirati nationals, the age- and sex-adjusted prevalences were 26/100 000 for males and 36/100 000 for females. The total incidence in Emirati nationals from 2010 to 2014 was 2.3/100 000 for ages 10 to 14 years and 7.2/100 000 for ages 15 to 19 years. By comparison with international cohorts, the incidence of pediatric-onset multiple sclerosis in Abu Dhabi is higher whereas gender distribution is similar.

Multiple Sclerosis, Anxiety, and Depression in the UAE: Does Social Stigma Prevent Treatment?

Background Depression rates in the multiple sclerosis (MS) population in the Arab world have rarely been reported despite people with MS generally having higher rates of depression. We examined depression rates in 416 people with MS versus the general population of Abu Dhabi, United Arab Emirates, and their treatment. Methods A retrospective medical record review of 416 people with MS (age range, 16-80 years) followed up at four large government hospitals in Abu Dhabi was conducted to determine the percentage of people with MS diagnosed as having depression or anxiety. Results The depression rate in people with MS (10.8%) was close to that in the general population of Abu Dhabi. The adjusted odds ratios of depression by selected variables showed that there was a significant difference (P = .003) between females and males in reporting depression, with more females reporting depression than males. Greater MS duration was also associated with a higher likelihood of being depressed (P = .025). The anxiety rate in the cohort (4.8%) was lower than that in the general Abu Dhabi population (18.7%). Conclusions The depression rate in people with MS in Abu Dhabi was close to that of the general Abu Dhabi population, but the anxiety rate in people with MS was lower. Explanations for these low rates include possible underreporting by patients and physician factors such as time limitations in busy clinics. Cultural aspects such as strong family support systems and religious factors in this predominantly Muslim population are also possible factors that warrant further investigation.

Prevalence and characteristics of transverse myelitis and neuromyelitis optica spectrum disorders in the United Arab Emirates: A multicenter, retrospective study

To determine the epidemiology and characteristics of transverse myelitis (TM) and neuromyelitis optica spectrum disorders (NMOSD) in Abu Dhabi, United Arab Emirates.