Difference between immunosuppressants and immunomodulators
Answers
Answered by
8
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
We aim to compare the efficacy and acceptability of immunomodulators and immunosuppressants to treat participants with RRMS and to generate a clinically useful hierarchy of available immunotherapies according to their efficacy and acceptability.
Multiple sclerosis (MS) is an inflammatory disorder of the brain and spinal cord resulting from interaction between unidentified environmental factors and susceptibility genes. Several pathological processes occur in MS involving the immune system, T‐cell‐mediated and B‐cell‐mediated mechanisms, demyelination, remyelination, microglial activation, and chronic neurodegeneration (Bennett 2009; Compston 2008). The sequential involvement of these processes influences the clinical course, which is characterized by attacks of neurological dysfunction with recovery, attacks leaving persistent deficits, and progression that causes permanent physical and cognitive disability. MS is among the most common causes of neurological disability in young people, with an annual incidence ranging from 2 to 10 cases per 100,000 persons per year and a north‐south gradient, lower incidence being closer to the equator. Its clinical manifestations typically occur between 20 and 40 years of age, with symptoms and signs involving different regions of the central nervous system: optic nerve, brainstem, cerebellum, cerebral hemispheres, spinal cord.
MS has a chronic course that evolves over 30 to 40 years. The clinical phenotypes include relapsing‐remitting MS (RRMS), secondary‐progressive MS (SPMS), primary‐progressive MS (PPMS), and progressive‐relapsing MS (PRMS) (Lublin 1996). The development of progression after a relapsing‐remitting course is responsible for permanent long‐term disability; it supervenes in about 80% of RRMS patients by 20 to 25 years from disease onset (Kremenchutzky 2006). Times to need assistance to walk, be confined to bed, or have died were 14, 24, and 45 median years from disease onset and 3, 12, and 30 median years from onset of secondary progression, respectively (Scalfari 2014).
Male sex, older age at onset, and high early relapse frequency (more than three attacks during the first three years) predicted significantly higher risk of conversion to SPMS and shorter latency to progression (Scalfari 2014). In RRMS patients, the onset of secondary progression is the determinant of long‐term prognosis, and its prevention is the key therapeutic goal.
According to the older Poser criteria (Poser 1983), MS can be clinically diagnosed by demonstrating two separate clinical attacks (dissemination in time) involving at least two different areas of the central nervous system (dissemination in space). The 2001 McDonald criteria and their 2005 and 2010 revisions incorporate magnetic resonance imaging (MRI) criteria for dissemination in space and time, allowing a MS diagnosis at the time of first symptoms (McDonald 2001; Polman 2005; Polman 2011). Dissemination in space is demonstrated by greater than or equal to oneT2 lesion in at least two MS typical central nervous system regions (periventricular, juxtacortical, infratentorial, spinal cord). Dissemination in time is demonstrated by: (i) simultaneous asymptomatic contrast‐enhancing and non‐enhancing lesions at any time; or (ii) a new T2 and/or contrast‐enhancing lesions(s) on follow‐up MRI, irrespective of its timing. The diagnostic criteria include exclusion of other possible diagnoses.
A declining trend in on‐study relapse rate (one of the most commonly used primary outcomes in MS trials) of placebo participants in trials has been observed (Inusah 2010; Nicholas 2012; Steinvorth 2013; Stellmann 2012). This decline is thought to result from decreasing pretrial relapse rates and a shorter time period over which pretrial relapse rates were calculated in newer trials (Steinvorth 2013; Stellmann 2012). Pre‐study relapse rate was found to be the best predictor for on‐study relapse rate. Other participant characteristics have changed in newer trials. Participants were older and with longer disease duration, whereas Expanded Disability Status Scale (EDSS) scores remained relatively stable. The introduction of the new McDonald criteria led to inclusion in newer trials of participants who had had earlier diagnosis and were later in their disease course, which was less severe compared to patients in older studies (Steinvorth 2013). These changes may explain the decrease in pretrial relapse rate and the associated decrease in on‐trial relapse rate. Unwelcome consequences of the expected decreased event rate were that the sample size of newer trials has been inflated and follow‐up periods shortened.
Another difference between older and newer studies is that the latter can have included participants who had made prior use of immunomodulators or immunosuppressants.
✌⤴⤴⤴⤴⤴⤴⤴⤴⤴⤴⤴⤴⤴✌
We aim to compare the efficacy and acceptability of immunomodulators and immunosuppressants to treat participants with RRMS and to generate a clinically useful hierarchy of available immunotherapies according to their efficacy and acceptability.
Multiple sclerosis (MS) is an inflammatory disorder of the brain and spinal cord resulting from interaction between unidentified environmental factors and susceptibility genes. Several pathological processes occur in MS involving the immune system, T‐cell‐mediated and B‐cell‐mediated mechanisms, demyelination, remyelination, microglial activation, and chronic neurodegeneration (Bennett 2009; Compston 2008). The sequential involvement of these processes influences the clinical course, which is characterized by attacks of neurological dysfunction with recovery, attacks leaving persistent deficits, and progression that causes permanent physical and cognitive disability. MS is among the most common causes of neurological disability in young people, with an annual incidence ranging from 2 to 10 cases per 100,000 persons per year and a north‐south gradient, lower incidence being closer to the equator. Its clinical manifestations typically occur between 20 and 40 years of age, with symptoms and signs involving different regions of the central nervous system: optic nerve, brainstem, cerebellum, cerebral hemispheres, spinal cord.
MS has a chronic course that evolves over 30 to 40 years. The clinical phenotypes include relapsing‐remitting MS (RRMS), secondary‐progressive MS (SPMS), primary‐progressive MS (PPMS), and progressive‐relapsing MS (PRMS) (Lublin 1996). The development of progression after a relapsing‐remitting course is responsible for permanent long‐term disability; it supervenes in about 80% of RRMS patients by 20 to 25 years from disease onset (Kremenchutzky 2006). Times to need assistance to walk, be confined to bed, or have died were 14, 24, and 45 median years from disease onset and 3, 12, and 30 median years from onset of secondary progression, respectively (Scalfari 2014).
Male sex, older age at onset, and high early relapse frequency (more than three attacks during the first three years) predicted significantly higher risk of conversion to SPMS and shorter latency to progression (Scalfari 2014). In RRMS patients, the onset of secondary progression is the determinant of long‐term prognosis, and its prevention is the key therapeutic goal.
According to the older Poser criteria (Poser 1983), MS can be clinically diagnosed by demonstrating two separate clinical attacks (dissemination in time) involving at least two different areas of the central nervous system (dissemination in space). The 2001 McDonald criteria and their 2005 and 2010 revisions incorporate magnetic resonance imaging (MRI) criteria for dissemination in space and time, allowing a MS diagnosis at the time of first symptoms (McDonald 2001; Polman 2005; Polman 2011). Dissemination in space is demonstrated by greater than or equal to oneT2 lesion in at least two MS typical central nervous system regions (periventricular, juxtacortical, infratentorial, spinal cord). Dissemination in time is demonstrated by: (i) simultaneous asymptomatic contrast‐enhancing and non‐enhancing lesions at any time; or (ii) a new T2 and/or contrast‐enhancing lesions(s) on follow‐up MRI, irrespective of its timing. The diagnostic criteria include exclusion of other possible diagnoses.
A declining trend in on‐study relapse rate (one of the most commonly used primary outcomes in MS trials) of placebo participants in trials has been observed (Inusah 2010; Nicholas 2012; Steinvorth 2013; Stellmann 2012). This decline is thought to result from decreasing pretrial relapse rates and a shorter time period over which pretrial relapse rates were calculated in newer trials (Steinvorth 2013; Stellmann 2012). Pre‐study relapse rate was found to be the best predictor for on‐study relapse rate. Other participant characteristics have changed in newer trials. Participants were older and with longer disease duration, whereas Expanded Disability Status Scale (EDSS) scores remained relatively stable. The introduction of the new McDonald criteria led to inclusion in newer trials of participants who had had earlier diagnosis and were later in their disease course, which was less severe compared to patients in older studies (Steinvorth 2013). These changes may explain the decrease in pretrial relapse rate and the associated decrease in on‐trial relapse rate. Unwelcome consequences of the expected decreased event rate were that the sample size of newer trials has been inflated and follow‐up periods shortened.
Another difference between older and newer studies is that the latter can have included participants who had made prior use of immunomodulators or immunosuppressants.
✌⤴⤴⤴⤴⤴⤴⤴⤴⤴⤴⤴⤴⤴✌
Attachments:
Answered by
16
Immunomodulators:- These modulate the activity of a patient's immune response, either up or down, until a desired level of therapeutic effect is reached. Cytokines are natural immunomodulator secreted by one type of immune cell that elicits response in another type of immune cell, these include interleukins, interferons and tumour necrosis factors. There are two general clinical approaches of immunomodulation.
Immunotherapy:- It is a treatment process which involves suppression of immune responses, to achieve therapeutic effects. Manipulation of the immune response can be carried out by modulating various components involved in this process.
Similar questions
Math,
7 months ago