CMSC and ACTRIMS Cooperative Meeting Highlights (2013)

Highlights from the Fifth Cooperative Meeting of The Consortium of Multiple Sclerosis Centers (CMSC) and Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), held in Orlando, Florida, May 29 through June 1, 2013

Written by Margaret M. McCormick, RN, BSN, MSCN
Reviewed by Jack Burks, MD, MSAA’s Chief Medical Officer
Edited by Susan Wells Courtney

The largest and most comprehensive meeting on multiple sclerosis (MS) care and research in North America took place May 29 through June 1 in Orlando, Florida, combining the 27th Annual Meeting of CMSC and the 18th Annual Meeting of ACTRIMS. This meeting is unique in that it brings together researchers and clinicians from across the spectrum of MS care, including physicians, nurses, physical and occupational therapists, psychologists, social workers, pharmacists, rehabilitation specialists, and advocacy professionals.

The interdisciplinary philosophy of CMSC addresses the fact that the course of MS in each individual is uncertain and the focus of treatment ever-changing – from physical, to social, to vocational, to emotional. Information presented at this meeting allows clinicians to integrate the newest scientific findings as quickly as possible into their clinical practice.

As its mission, ACTRIMS provides leadership in the field of multiple sclerosis and other demyelinating diseases. Founded by MS clinicians and researchers, ACTRIMS serves as the US and Canadian counterpart to ECTRIMS, the European Committee on Treatment and Research in Multiple Sclerosis. ACTRIMS’ annual meetings provide a forum to exchange information, debate current issues, and discuss advances related to basic and clinical issues in MS research.

This summary of the CMSC and ACTRIMS Fifth Cooperative Meeting includes topics of particular interest to those directly affected by MS and may also address informational needs of MS healthcare professionals. To provide a sense of the multidisciplinary spirit of the meeting, information about physical, psychological, and medical issues is presented.

New Treatments under Review by the FDA

Lemtrada® (alemtuzumab, formerly Campath), is given intravenously each day for five days and again one year later each day for three days. (For a summary of research conducted to support approval for relapsing-remitting MS [RRMS], please see MSAA’s MS Research Update 2013. Lemtrada has been submitted to the United States Food and Drug Administration (FDA) for approval; a decision is expected in 2013.

In a subset of patients with highly active disease in the CARE-MS II trial, 24 percent of individuals treated with Lemtrada were free of disease activity at the end of the two-year study, while none of the study participants treated with Rebif® (interferon beta-1a) achieved that outcome. These same individuals were followed after the two-year trial period in an extension study. Fewer patients receiving Lemtrada versus Rebif experienced relapses, sustained accumulation of disability, gadolinium-enhancing lesion activity, and T2-lesion activity.

Immune thrombocytopenia (ITP) is a very rare, adverse effect caused by the treatment of RRMS with Lemtrada. With ITP, the blood does not clot as it should, and this can result in internal bleeding. It is important that patients commit to monthly lab and self-monitoring because, if not detected and treated, ITP can have grave consequences. When treated promptly, ITP caused by drug treatments such as Lemtrada, responds readily to treatment with oral steroids.

Plegridy™ (peginterferon beta-1a) is under investigation in the ADVANCE study as a less-frequently injected alternative to the currently available disease-modifying therapies (DMTs) for RRMS. On May 21, 2013, Biogen Idec submitted this new treatment to the FDA for approval.

Results were presented from the first year of this Phase III study, where 1,512 patients were randomized to one of three groups: one group receiving placebo; a second group receiving Plegridy given by subcutaneous injection (referring to “under the skin”) once every two weeks; and a third group receiving Plegridy by subcutaneous injection once every four weeks.

Plegridy significantly reduced MS disease activity, including relapses, disability progression, and brain lesions, compared to placebo at one year. The overall incidence of serious adverse events (SAE) and adverse events (AE) was similar among the Plegridy and placebo groups. The most common serious adverse event was infection, which was balanced across all treatment groups (less than or equal to 1 percent per group). The most commonly reported adverse events with Plegridy treatment were redness at the injection site and influenza-like illness.

Experimental Therapies

The two-year follow-up results of the HALT study were reported. This is a Phase II clinical trial of high-dose immunochemotherapy and autologous hematopoietic cell transplantation (HCT). A pilot study in Europe has previously tested this technique in 19 MS patients with RRMS. Eighteen (18) of those treated had their disease stabilize or improve for at least three years following treatment.

The HALT Phase II study was conducted in patients with highly active RRMS who had failed conventional therapy. The treatment induced a high rate of sustained remissions at two years. Study participants will be followed for five more years to see how long the benefits of this treatment may continue.

New Studies with Tysabri and PML

Tysabri® (natalizumab) is administered by IV infusion once every four weeks and is generally recommended for individuals with RRMS who have not responded adequately to or cannot tolerate other MS medications. For additional information on Tysabri, please see MSAA’s MS Research Update 2013.

Progressive Multifocal Leukoencephalopathy (PML) is a potentially fatal brain infection with the JC virus (JCV), which can occur in people with weakened immune systems, including individuals with MS who are being treated with Tysabri. Risk factors include: the presence of anti-JCV antibodies (as detected by the Stratify JCV Antibody ELISA test); longer duration of Tysabri treatment, especially after two years; and prior treatment with an immunosuppressant medication. The combination of these factors brings the risk to as high as 11 in 1,000 (or slightly more than one percent). For more information, please see MSAA’s article, “Antibody Test Identifies New Risk Factor for PML.”)

The risk of PML in JCV antibody-negative patients treated with Tysabri is very low (1 in 10,000). The presence of JCV antibody in these patients is a known risk factor for PML. In this analysis, the risk of PML for individuals with low levels of JCV antibody was several-times lower compared with the risk attributed to all JCV antibody-positive patients.

As the use of Tysabri in early MS has not been widely studied, 300 individuals with early RRMS who are JC virus antibody negative will be followed over the course of four years while undergoing treatment with Tysabri. The purpose of the study is to find out if any assessments might predict whether or not patients receiving Tysabri will remain free of disease, and also to determine how effective Tysabri is at keeping patients who are in the early stages of RRMS free of disease. For information on enrolling in the trial, please visit www.clinicaltrials.gov, study # NCT01485003.

Patients who discontinue treatment with Tysabri may experience a relapse or develop new enhancing lesions. Results were reported for five individuals who were treated with Acthar® Gel (80 units subcutaneously), an FDA-approved treatment option for MS relapses. This treatment was given for five days at week four, at two months, and at three months, after discontinuing Tysabri. Four of these patients also received Copaxone® (glatiramer acetate), and one participant received intravenous immunoglobulin (IVIG). IVIG is not approved by the FDA specifically for MS relapses, but is sometimes used for individuals who are experiencing a severe relapse and are not responding to other treatments. None of the five patients developed a new enhancing lesion or symptoms of a clinical relapse during up to 12 months of follow-up.

Studies in Progressive MS

Certain outcomes for individuals with primary-progressive MS (PPMS) are similar to those with RRMS. Despite the added challenges that PPMS can pose, a study that looked at members of both PPMS and RRMS populations reported similar outcomes with respect to health-related quality of life, depression, fatigue, and anxiety.

The potential of Rituxan® (rituximab) treatment in secondary-progressive MS (SPMS) is under consideration. A retrospective chart review of 30 SPMS patients treated with Rituxan was conducted in order to begin to understand the safety and effectiveness of Rituxan treatment in this population. EDSS, 25-foot walk, and nine-hole peg test results were evaluated. In the two years prior to Rituxan treatment, evaluation of these scores suggested disease progression. In contrast, in the two years following Rituxan treatment, no significant differences occurred in the scores. This suggests that patients were at least stabilized on treatment.

No significant adverse reactions were reported. The authors concluded that Rituxan therapy in treatment of SPMS could stabilize, and potentially reverse, the rate of disease progression. Larger studies are required to validate these results. For additional information on rituximab, please see MSAA’s MS Research Update 2013.

Pregnancy while Taking DMTs

Because DMTs are not tested in pregnant women, information about the potential risks of fetal exposure is not available to guide decision-making by women who are pregnant or wish to become pregnant. Gathering as much information as possible on this important question is critical to women with MS during child-bearing years. Although women are advised to use birth control and to discontinue DMTs when they wish to become pregnant, fetuses are exposed during unexpected pregnancies or with the intentional use of DMTs during pregnancy. The outcomes of these pregnancies are monitored during clinical trials and through pregnancy registries following product approval.

Final Results from the Betaseron® (interferon beta-1b) Pregnancy Registry were presented. Data were presented on 96 pregnancies, and no pattern was seen to suggest increased negative outcomes (such as fetal abnormalities) with Betaseron. Continued monitoring is recommended.

Pregnancy data on Tecfidera™ (dimethyl fumarate, formerly known as BG-12) was provided from the BG-12 Development Program. Pregnancy outcomes are known for 25 of the 35 pregnancies exposed to Tecfidera. To date, pregnancy data indicate no increased risk of fetal abnormalities or adverse pregnancy outcomes associated with exposure to Tecfidera during the first trimester. Further data regarding pregnancies will be collected through a pregnancy registry.

As part of the Gilenya® (fingolimod) Pregnancy Registry, the design of a study was presented that will follow up to 500 women who have become pregnant after being exposed to at least one dose of Gilenya. This information will be compared to information from the US Centers for Disease Control and the European Surveillance of Congenital Anomalies. The comparison will provide information about the safety for mother and fetus, in connection to treatment with Gilenya during pregnancy. To enroll in this study, please visit www.clinicaltrials.gov, study # NCT01285479.

Pregnancy Outcomes in Aubagio® (teriflunomide) Phase II/III clinical trials were reported. Of the 71 pregnancies studied, 44 patients received Aubagio, and 27 received either interferon beta or placebo. No teratogenicity (production of birth defects) was reported in newborns of females exposed to Aubagio, or female partners of males exposed to Aubagio. The company plans a pregnancy registry to gather additional information.

Editor’s note: While the data presented on pregnancy was encouraging, as a limited number of women who became pregnant on DMTs did not see abnormalities in their babies, individuals with MS need to be strongly cautioned. These are small numbers and do not suggest that getting pregnant is considered safe while taking DMTs. The recommendations of the FDA and MS experts still stand for women on DMTs to take preventative measures to avoid pregnancy.

Emotional Findings

Treatment with disease-modifying therapies (DMTs) improves the level of mental health. Despite any decreases in the level of physical health over a three-year time period, individuals who were treated with DMTs experienced an improvement in mental health over the same time period. The average age of the sample at the beginning of the study was 39.2 years and the average Expanded Disability Status Scale (EDSS) score was 2.4 (ambulatory with minimal to mild disability). Differences in both the worsening of physical health and the improvement in mental health were stronger in men than in women.

A study found that the level of disability does not impact the frequency of depression. In this study, no correlation was found between disability as measured by the EDSS or number of relapses and depression. Patients who were married and living with family were least likely to be depressed.

Depression in MS is frequent, under-diagnosed, under-treated, and has a high effect on quality of life. Screening for depression should also be conducted during follow-up visits to help diagnose and resolve this debilitating symptom.

Physical Findings

Findings on the barriers and facilitators to exercise in people with MS were presented. Using an online questionnaire and focus groups, the authors determined that balance and fatigue are the greatest barriers to exercise. They also found that a decrease in MS symptoms (that result from exercise) was the greatest motivator to exercise.

Intermittent strength training was found to be more effective than continuous strength training for people with MS. Fatigue can prevent individuals with MS from performing enough repetitions of strength training exercises to be effective. In this study, individuals with MS who performed straight-leg exercises intermittently, versus continuously, were able to do more repetitions (115 versus 32). The authors suggest that intermittent training may provide a means by which members of the MS community can perform a greater volume of training and thus realize greater therapeutic gains.