A Quest for Recovery

On July 25, 2014 I had my first infusion of Rituxan. This blog chronicles the experiences of myself and other people who are on Rituximab for the treatment of Multiple Sclerosis. I found little information that detailed what improvements people had, I was only able to find statistical data on lesions and symptoms. For this reason I want to collect stories of people's experiences while on Rituxan. I'm inviting you to share. If you have a story to tell, please submit it in the link at the top of my page. Positive and negative stories are welcome, but please keep the language SFW so as not to insult anyone. Thank you.

[rituximabjourney]

Month Three and Counting

Okay, just in case someone new is just starting to reading this site, I am commenting monthly to see if the infusions of Rituximab are having any noticeable positive effect.  As with last month, things have changed.  Last post it was the daily temperatures decreasing from being in the 100s, over this last month the changes had to do with additional stress. My mother has been diagnosed with esophageal cancer, my work environment is still in flux involving remodeling and IT changes, my husband has been battling a health issue since August and last Friday I had to put a much beloved pet to sleep.  Life happens, but not always the way we desire.  I am feeling stressed.

That said here is my list:

NUMBNESS IN EXTREMITIES - I either am getting use to the "tingles" in my left leg or they are gone.  I am still successfully standing longer when working out and when teaching.  I no longer feel that my walking after a workout is shaky. I still need a cane to walk without weaving like a drunkard though.  I think I feel a bit more confident.

HAND TREMORS - Still not my issue anymore, was an issue 5 years ago

HAND STRENGTH - I continue to have confidence in my grip on both light and slightly heavy objects.

BLADDER CONTROL - Seems favorably improved over what it has been like the last two months. 

BOWEL CONTROL - No noticeable change, again forgive me for not going into details

MEMORY - Last month I said "I seem more focused and I have not increased my drugs to support this."  I still feel this "focus."

VERBAL SKILLS - No noticeable change, still forget words occasionally.  This frustrates me because the words I lose are common words like "pillow".

DEPRESSION - This last month I am sad to say I have been fighting negative thoughts.  When I am like this I doubt others intentions and I doubt my self worth and value.  I recognize that my stress levels maybe triggering this turn. 

LEG PAIN - I still have little pain except at night.  (I still want a new mattress.)

HAND PAIN - My hands are still not feeling painful right now.  I shook hands with someone and braced for the shot of pain and it wasn't too bad. Nice change!

ARM PAIN - Same with my arms, very little pain.  Being touched seems OK.

FATIGUE - Mostly I am not feeling too fatigued but I have had a couple of episodes where I suddenly have become very sleepy.

BALANCE WHEN STANDING - I have notice that my balance is still what I would call as being better.  Last night I put my feet together and closed my eyes.  I did not fall to the right as I have immediately done the last few years.

BALANCE WHEN WALKING - I don't feel as unsteady as I walk, accept when I have been been active, such as housework or cooking. By unsteady I mean that I fear falling because of my balance.  I haven't fallen while just walking in more than a month.  I do have trouble walking a straight line without an aid.

ABILITY TO WALK UNASSISTED AT HOME - No change, do not use cane at home, but must have light to be able to walk.

ABILITY TO WALK UNASSISTED WHILE SHOPPING - Still using a w-chair most of the time but I will try walking the store if I know the trip will not be a long one.

ABILITY TO EXERCISE - Still working with trainer twice a week.  He is trying to keep me moving constantly for 1 hour.  I rode a stationary bike for 35 minutes!  He thought I would lose my legs at 20.  Woo Woo!

ABILITY TO CARRY AN OBJECT LARGER THAN A BREADBOX - I still do not feel confident when walking and carrying, but I did successfully give it a try this month with carrying in the groceries.

ABILITY TO DO HOUSEWORK CONTINUOUSLY FOR AN HOUR - My threshold is still 30 minutes.

ABILITY TO DRESS,BATH, COMB HAIR, APPLY MAKE UP - No change, I am trying to stand more but I find it hard after relying on a chair for so long.

ABILITY TO WORK - Still using a w-chair

I have had no unusual infections.  (Happy Face)

[rituximabjourney]

2 Months Later - Feeling a bit better

As I posted previously, I plan to comment monthly to see if the infusions have a noticeable positive effect.  My environment has had a significant change in that the temperatures are no longer in the 100s and yes I feel better just because of that.

NUMBNESS IN EXTREMITIES - Left leg still tingles more than 3 months ago  but I still cannot feel the vibration of a tuning fork in either leg.  I am standing longer when working out but my walking after a workout is still  shaky.

HAND TREMORS - Not my issue anymore, was an issue 5 years ago

HAND STRENGTH - I have noticed that I haven't lost the grip on what I am holding lately. 

BLADDER CONTROL - Seems favorably improved over what it has been like the last two months.  I can't say it is better than before the treatment.

BOWEL CONTROL - No noticeable change, forgive me for not going into details

MEMORY - Last month I said "No noticeable change, still forgetting names and instructions, using written notes".  This month I seem more focused and I have not increased my drugs to support this.

VERBAL SKILLS - No noticeable change, still forget words occasionally

DEPRESSION - I still feel a noticeable improvement, feel very up-beat even though things a work are a little crazy because of remodeling of my work space.

LEG PAIN - Actually I have little pain except at night.  I blame my mattress (because I want a new one)

HAND PAIN - My hands are not feeling painful right now, or for the last couple of weeks.

ARM PAIN - Same with my arms, very little pain.  Touching seems OK.

FATIGUE - Got much worse after the first infusion, now I am a little tired but I am not falling a sleep suddenly in the afternoons anymore. 

BALANCE WHEN STANDING - I have notice that my balance is better than the last two months.

BALANCE WHEN WALKING - I don't feel as unsteady as I walk, even when I am tired.

ABILITY TO WALK UNASSISTED AT HOME - No change, do not use cane in home, but must have light to be able to walk.

ABILITY TO WALK UNASSISTED WHILE SHOPPING - Still using a w-chair most of the time but I did try walking the store a couple of times when I knew the trip would not be a long one and I did OK.

ABILITY TO EXERCISE - Still working with trainer twice a week

ABILITY TO CARRY AN OBJECT LARGER THAN A BREADBOX - Do not feel confident when walking and carrying still.  I am afraid I don't trust my ability to do this so I don't try.

ABILITY TO DO HOUSEWORK CONTINUOUSLY FOR AN HOUR - Still trying to clean, but 20 to 30 minutes still seems to be my threshold.

ABILITY TO DRESS,BATH, COMB HAIR, APPLY MAKE UP - No change, I do sit while doing most of these things

ABILITY TO WORK - Still using a w-chair

The hot summer temps are gone and I do accept that some of my  improvements are do to that I am sure.  I have had no unusual infections and I did catch a cold, but fought it off in the time I would have expected to.  So far so good.

[rituximabjourney]

Why I work

Needing to be moving is very tiring and hard and I have to stop and rest at some point or fall down.  But having a reason to move, a goal to obtain makes the effort easier to endure. 

For me, working at this school with these kids makes me feel better than any pill they give me for my fatigue.  I can't clean my house on my own but I choose a project each weekend to keep me moving forward. 

Last weekend I cleaned my pantry. It took me two days but I got it done.  I am afraid that if I stop working or stop setting little person project goals for myself, then the MS will succeed in knocking me down and out of life.

I refuse to relinquish control to my MS.

[rituximabjourney]

I guess this is called an "Editorial"

On August 17th I posted a blog regarding an article titled Experimental Medications: Rituximab and Ocerelizumab.  At the end of the section on rituximab the writer wrote,

"Rituxan is not likely to be further developed for FDA approval. However, next-generation anti-CD20 monoclonal antibodies have been developed to build on the encouraging data from Rituxan’s MS studies, including ocrelizumab, as discussed in the following entry."

If you want the full article go back in my achives to 8/17/14.  I believe I originally copied the articles from the National MS Society's page on experimental medicines.

Well both Rituximab and Ocerelizumab are out of Genetech.  I was wondering why Genetech didn't continue on to Phase 3 testing on Rituximab to get FDA approval instead of stopping the process to concentrate on starting trials for Ocerelizumab which I understand is a tweaking of the Rituximab formula.  I think they added an enzyme or something. Couldn't they get the one drug out there to help people and then later come out with a new and improved version?

Why wouldn't a drug company rush to expand the approved uses on a drug already in production?  Why wait?  Don't they know that the people who could be helped by the already proven drug probably don't have another 10 years to wait? 

IS THE MAIN CONSIDERATION PROFIT?  By working to get Ocerelizumab through the testing phases are they now able to charge a whole lot more money then they would have been able to charge for Rituximab?  Are the benefits of the new drug any different than the old drug?

Also, what about our different diagnoses.  I read that there has been different drug trials of Rituximab targeting RRMS, PPMS and SPMS.  I think the testing for Ocerelizumab may only have targeted RRMS.  That leaves the rest of us out of the FDA approval.

Our western medical system has been built on a foundation rooted in what is or is not profitable.  I am guessing that the definition of "not profitable" includes "not enough profit." Maybe the Ferengi are running our drug companies (Star Trek reference for you kiddies) and sadly we are not heading toward Gene Roddenberry's vision of the future where medical care and medicines are developed to cure and protect, because it is the right thing to do.

Now to be fair, prior to the 1990's there really weren't any approved drugs to treat MS and today, 25 years later, there are more than a handful of drugs developed to fight MS so we do need to also be thankful to drug companies for their research. Maybe in another 25 years researchers will have been able to identify what causes MS to develop and will have found a way to stop it. (But where's the profit in that? -- Always the pessimist)

[rituximabjourney]

Recovery Search

Regarding my last post titled Multiple Sclerosis Discovery Forum, the Status/Outcome on one of the trials seems to say that Rituximab may halt progression, but it does not site patient physical improvement as an outcome. 

Drat! I want some recovery of function.

Doesn't mean I won't have some.  I will stay positive.

[rituximabjourney]

Multiple Sclerosis Discovery Forum

I have found this site and I am sharing some edited down information.  I need to explore the site some more to see what the site has to offer. 

The more we know, the better we can participate in making decisions about our treatment.

After providing basic drug information, there is data on 10 different clinical trials. 3 against a placebo - 7 head to head studies.  4 trials look exclusively at Relapsing Remitting (RRMS), 1 trial looks exclusively at Primary Progressive (PPMS), 2 trials look at Secondary Progressive (SPMS) 

Just look for the "Status/Outcome" data if you are wanting to skip all the technical data.

Article:

Multiple Sclerosis Discovery Forum (Edited)

http://www.msdiscovery.org/research-resources/drug-pipeline/229-rituximab

(website has complete listing of footnote references on all data below)

Last updated: 6 Sep 2014

Rituximab

Summary

Trade name: 

Rituxan

MabThera

MabThera SC (subcutaneous version)

Mabtas (biosimilar version)

Class: 

Immunosuppressor (3) (6)

Target: 

B cells (3)

CD20 (3)

Status for MS: 

Results from Phase II trials for RRMS have been published (2009, 2010) (12) (13)

Used off-label to treat MS (15)

Administration: 

Intravenous infusion (8)

Example of frequency of intravenous infusions in clinical trials is two 1000 mg infusions every 24 weeks (12)

Results presented at a meeting indicate that subcutaneous administration is a non-inferior alternative to intravenous infusion, which would allow administration over 5 minutes rather than 2.5 hours (8 December 2012) (17)

Subcutaneous formulation is approved by the European Commission for treating non-Hodgkin lymphoma, allowing administration over 5 minutes (28 March 2014) (35)

Commercial: 

Discovered by Biogen Idec (16)

Co-marketed by Genentech and Biogen Idec in the US (16)

Co-marketed by Chugai and Zenyaku Kogyo Co. Ltd in Japan (16)

Marketed by Roche as MabThera elsewhere in the world (16)

Biosimilar version has been launched by Intas Pharmaceuticals in India (May 2013) (18)

Synonyms: 

HSDB 7455 (1)

IDEC-102 (1)

Immunoglobulin G1 (human-mouse monoclonal IDEC-C2B8 gamma1-chain anti-human antigen CD 20), disulfide with human-mouse monoclonal IDEC- C2B8 kappa-chain, dimer (1)

Mabtas (18)

Mab Thera (1)

MabThera (16)

Rituxan (1)

Rituximab (1)

UNII-4F4X42SYQ6 (1)

Systematic name: 

Immunoglobulin G1, anti-(human CD20 (antigen)(human-mouse monoclonal IDEC-C2B8 gamma1-chain), disulfide with human-mouse monoclonal IDEC- C2B8 kappa-chain, dimer (1)

Physiology

Class: 

Immunosuppressor (3) (6)

Target: 

B cells (3)

CD20 (3)

Properties: 

Genetically engineered chimeric murine/human monoclonal antibody that binds to CD20, a B cell antigen (6) (7)

Contains murine anti-CD20 antibody complementarity-determining regions and human kappa and IgG1 heavy-chain constant regions (8)

Molecular weight: 145 kD (8)

Produced in Chinese hamster ovarian cells (8)

Binding affinity for CD20 is ~8 nM (8)

Mean half-life in serum in patients with B cell lymphoma receiving intravenous infusion is 59.8 hours, although range is wide (8)

Half life is 20 days in patients with rheumatoid arthritis (after receiving second dose) (8)

Serum levels generally increase as doses are repeated and levels of CD20 decrease (7)

Mechanisms/Effects

Human: 

Complete mechanism unknown (14)

Targets the antigen CD20, which is expressed on pre-B cells and mature B cells (6) (11), as well as on a small subset of T cells (42)

Rapidly eliminates mature circulating B cells for up to 6 to 9 months (3) (4) (8)

Decreases or eliminates B cells in the cerebrospinal fluid of MS patients (14)

Affects chemokine levels in the cerebrospinal fluid of MS patients, such that levels of CXCL13 and CCL19 are reduced (14)

Reduces T cell levels in the cerebrospinal fluid of many MS patients, possibly because B cells (depleted by drug) influence T cell trafficking into the central nervous system by affecting chemokine production (14)

Depletes CD3+ CD20(dim) T cells (a subset of cells that is increased in MS) from individuals with MS (42)

May induce cell death through apoptotic pathways involving caspase-3 activation, as shown by studies of chronic lymphocytic leukemia patients (7)

Can cause complement activation, resulting in cell lysis (complement-dependent cytotoxicity), but the strength of the effect varies depending on the B-cell lymphoma cell line studied and does not correlate with clinical responses to the drug (7)

May act through antibody-dependent cellular cytotoxicity (in which cells are killed by effector cells that have been activated by the Fc portion of rituximab bound to the lymphoma cell) (7)

Binding to CD20 induces intracellular signaling pathways, and if crosslinked, the degree of signaling increases, as shown with studies of malignant B cells (7)

Binding to CD20 induces intracellular signaling, and the result of such signaling (such as apoptosis or cell cycle arrest) appears to depend on the cell line studied (7)

Appears to reduce axonal damage (as determined by measuring levels of the axonal damage biomarker neurofilament light protein in cerebrospinal fluid) in progressive MS (after 12 to 24 months of treatment) (19)

Intrathecal treatment depletes B cells in the central nervous system, which leads to a strong reduction in the increased levels of tumor necrosis factor-alpha (which can cause excitotoxic damage) and neurofilament light protein (a marker of axonal damage) in the cerebrospinal fluid, based on analysis of an individual with progressive MS (24)

Generally appeared safe and effective in a study involving 3 pediatric patients (2 with RRMS and 1 with SPMS) (39)

Repeated intrathecal doses (to target compartmentalized inflammation) reduced (i) peripheral CDC20+ B cells, (ii) several central proinflammatory cytokines, and (iii) neurodegeration markers, but did not affect oligoclonal bands, in an individual with severe progressive MS (43)

Negative effects: 

Angina (16)

Anthralgia (16)

Bronchospasm (4)

Cardiac arrhythmias (16)

Hypertension (16)

Hypotension (4)

Hypoxia (4)

Infections (16)

Infusion-related reactions (15)

Nausea (16)

Pyrexia (16)

Progressive multifocal leukoencephalopathy (3)

Strongly reduces antibody response to pandemic H1N1 influenza vaccine in individuals with arthritis (32)

Viral reactivation (16)

May lead to immunosuppression-related reactivation of the hepatitis B virus in previously-infected individuals; the US Food and Drug Administration requires this information to be displayed in a boxed warning (25 September 2013) (27)

Commercial: 

Discovered by Biogen Idec (16)

Co-marketed by Genentech and Biogen Idec in the US (16)

Co-marketed by Chugai and Zenyaku Kogyo Co. Ltd in Japan (16)

Marketed by Roche as MabThera elsewhere in the world (16)

Biosimilar version has been launched by Intas Pharmaceuticals in India (May 2013) (18)

Key Clinical Trials

Placebo-controlled Trials: 

Trial name: 

Double Blind Combination of Rituximab by Intravenous and Intrathecal Injection Versus Placebo in Patients With Low-Inflammatory Secondary Progressive Multiple Sclerosis (RIVITaLISe) (recruiting as of January 2014) (33)

Phase I/Phase II trial (33)

Study Design: 

Government institute-sponsored, double-blind, placebo-controlled trial to examine the effects of combined systemic and intrathecal rituximab (to ensure that the drug reaches the central nervous system) on brain atrophy (primary outcome measure) (33)

Disease Stage: 

SPMS (33)

Enrollment/Number of Patients: 

80 (estimated) (33)

Duration: 

3 years (1 year of pretreatment visits followed by 2 years of treatment) (33)

Status/Outcome: 

Recruiting as of January 2014, estimated completion date, September 2016 (33)

Trial name:

Hawker et al., Ann. Neurol., Oct 2009 trial (12)

Phase: 

Phase II/III trial (12)

Study Design: 

Randomized, double-blind, placebo-controlled, multicenter trial to evaluate the effects of rituximab (two 1000 mg infusions or placebo every 24 weeks) on time to confirmed disease progression (primary endpoint) and T2 lesion volume and total brain volume (secondary endpoints) (12)

Disease Stage: 

PPMS (12)

Enrollment/Number of Patients: 

439 (12)

Duration: 

96 weeks (12)

Status/Outcome: 

Drug was not associated with a decrease in time to confirmed disease progression (but there was a suggestion of a potential decrease in younger patients, especially those with inflammatory lesions) (12) (16)

Trial name: 

Hauser et al., N. Engl. Med., Feb 2008 trial (5)

Phase: 

Phase II trial (5)

Study Design: 

Double-blind, placebo-controlled trial to evaluate the effects of intravenous rituximab (1000 mg or placebo on weeks 1 and 15) on the total count of gadolinium-enhancing lesions (primary endpoint) and on the proportion of patients with relapses (5)

Disease Stage: 

RRMS (5)

Enrollment/Number of Patients: 

104 (5)

Duration: 

48 weeks (5)

Status/Outcome: 

Drug was associated with a reduced number of inflammatory brain lesions and a reduced number of relapses (14.5% vs 34.3% at week 24 and 20.3% vs 40% at week 48) (5)

Head-to-Head Trials: 

Other Trials: 

Trial name: 

He et al., Cochrane Database Syst. Rev., December 2013 study (31)

Phase: 

Retrospective clinical trial review (31)

Study Design: 

Review of all randomized, double-blind, controlled parallel group clinical trials that evaluated the effects of rituximab (versus placebo or another approved disease-modifying therapy) on MS, with a followup of at least 1 year; 1 trial (5) was included in this analysis (31)

Disease Stage: 

RRMS (31)

Enrollment/Number of Patients: 

104 (31)

Duration: 

1 year (31)

Status/Outcome: 

Analysis did not support the use of rituximab in MS because only 1 trial was included; a significant attrition bias at week 48 (24%), a small number of participants, and short duration meant that the quality of the study was limited (31)

Trial name: 

Evdoshenko et al., ISRN Neurol., September 2013 study (28)

Phase: 

Observational/open-label study (28)

Study Design: 

Prospective, observational pilot study to examine the effects of combined rituximab and mitoxantrone therapy (consisting of an intravenous infusion of 1000 mg methylprednisolone, 1000 mg rituximab, and 20 mg mitoxantrone on day 1 and 1000 mg methylprednisolone and 1000 mg rituximab on day 14) (28)

Disease Stage: 

Active MS (28)

Enrollment/Number of Patients: 

28 (28)

Duration: 

12 to 48 month observation period (28)

Status/Outcome: 

No relapses occurred during the observation period; CD19+ and CD19+/CD27+ B cells were depleted in all individuals in the peripheral blood and cerebrospinal fluid at 6 months; the CD19+/CD27+ memory B cell subset was depressed over longer time periods than the CD19+ cells (28)

Trial name: 

Castillo-Trivino et al., PLoS One, July 2013 study (21)

Phase: 

Retrospective trial review (21)

Study Design: 

Review of 4 clinical trials to evaluate the safety and efficacy of rituximab for treating MS (21)

Disease Stage: 

PPMS and RRMS (21)

Enrollment/Number of Patients: 

599 (21)

Duration: 

N/A (21)

Status/Outcome: 

The drug was associated with frequent mild or moderate adverse events, but generally appears safe for up to 2 years of treatment; it substantially reduces inflammatory disease activity (the annualized relapse rate and gadolinium-enhancing lesions seen on brain MRI scans) in RRMS, but only marginally delays disease progression in PPMS (21)

Trial name: 

Rituximab in Secondary Progressive MS (conference report, June 2013) (20)

Phase: 

Retrospective medical record review (20)

Study Design: 

Retrospective study to examine the effects of rituximab (at least 3 cycles of 1 g intravenous infusions 2 weeks apart, given every 6 months) in patients for whom conventional therapy had failed; the functional ability of these patients had declined significantly in the two previous years, such that their Expanded Disability Status Scale (EDSS) scores increased about 0.5 points per year (20)

Disease Stage: 

SPMS (20)

Enrollment/Number of Patients: 

25 (20)

Duration: 

At least 18 months (20)

Status/Outcome: 

Rituximab treatment was associated with reduced disease progression, such that mean EDSS scores after the third cycle of treatment were very similar to the mean scores one year before treatment began (20)

Trial name: 

Naismith et al., Neurology, Jun 2010 trial (13)

Phase: 

Phase II, open-label study (13)

Study Design: 

MRI-blinded, single-center study to evaluate the effects of rituximab (375 mg/m2 weekly for four weeks) on gadolinium-enhancing lesions (primary objective) in patients who had been treated with a standard injectable disease-modifying agent in the past 18 months but had shown an inadequate response and were then given rituximab as add-on therapy (13)

Disease Stage: 

RRMS (13)

Enrollment/Number of Patients: 

30 (13)

Duration: 

52 weeks, such that the drug was given for the first four weeks and MRI scans were performed monthly beginning 12 weeks after the first drug treatment (13)

Status/Outcome: 

Drug was associated with a reduction in the number of gadolinium-enhancing lesions, such that 74% of posttreatment MRI scans were free of gadolinium-enhancing activity versus 26% of baseline MRI scans (13)

Trial name: 

Bar-Or et al., Ann. Neurol., Mar 2008 trial (10)

Phase: 

Phase I trial (10)

Study Design: 

Open-label trial to evaluate the safety, tolerability, pharmacodynamics, and activity of two courses of rituximab (total dose, 4000 mg), six months apart, in MS (10)

Disease Stage: 

RRMS (10)

Enrollment/Number of Patients: 

26, with 22 completing the trial (10)

Duration: 

72 weeks (10)

Status/Outcome: 

The drug was not associated with any serious adverse effects, although mild and moderate infusion-associated events were seen; furthermore, the drug was associated with fewer new gadolinium-enhancing or T2 lesions (10)

[rituximabjourney]

Tackling Mountains (Kind-of)

I do not usually have a camera with me because I usually have my hands full with my cane or wheelchair.  I rarely think of "let's take a picture" except when we go on vacation.  I am behind technical gadget wise, no smart-phone.  I only yesterday created a Facebook page (Yeah, serious, Tumblr is the only social networking I have ever tried beyond emails and I don't post often on Tumblr).  It never occurred to me to ask someone to take a picture of me "at the mountain top".  That is why I am using the woefully insufficient picture of the LA Coliseum you see above.

My husband and I and a bunch of friends went to the USC vs. Fresno State game Saturday.  I intentionally did not take my wheelchair because that would have meant we wouldn't have been able to sit with our friends.  That is one of the things about having MS, or any other handicap, that makes going places like a sports competition NOT FUN.  Sure they accommodate the handicapped but the accommodation is usually no where near your friends so it is like your not part of the group, which is the purpose of going as a group!

Anyway, the parking lots around the Coliseum where the buses park aren't really too far from the gates, so I knew I could walk that far using my cane.  The gates are a bit uphill but not too bad.  I knew I could get to the gate on my feet.  I didn't think about getting to my seat beyond knowing there would be no handrail in the stands area.

The LA Coliseum has an escalator but not near where we were going to sit, so I told Frank I wanted to try the stairs. In the picture of the coliseum above, do you see those white lines coming outwards?  Those are stairways.  They go up at least three stories maybe four.  I CLIMBED THEM!!!!!!  Woo Woo!

Recently I read a blog I follow where a young women with MS described her vacation with her family, a vacation in the mountains and how she had hiked here and there.  For her that was a BIG deal because last year she was recovering from having lost all ability to walk and care for herself and now she is climbing mountains! 

I thought about how happy I was for her but also I thought about how I can't climb mountains.  I thought about how I am about to enter my 60s and I will retire in a few years and I wondered what places I could explore in my retirement.  In truth I was feeling a little sorry for myself because I can't go everywhere.

Well, I climbed a "mountain" at the stadium.  I climbed up and then back down.  I need to remember that there is joy in climbing little mountains too.

[rituximabjourney]

AFTER ONE MONTH

This list isn’t very scientific but I plan to comment monthly to see if the infusions have a noticeable positive effect.

NUMBNESS IN EXTREMITIES - Slight change in left leg

HAND TREMORS - Not my issue anymore, was an issue 5 years ago

HAND STRENGTH - No noticeable change, still dropping things

BLADDER CONTROL - Worse since first infusion

BOWEL CONTROL - No noticeable change, forgive me for not going into details

MEMORY - No noticeable change, still forgetting names and instructions, using written notes

VERBAL SKILLS - No noticeable change, still forget words occasionally

DEPRESSION - Noticeable improvement, feel very up-beat even in this heat

LEG PAIN - Increase pain in lower left leg

HAND PAIN - No noticeable change, still hurts to shake hands, or hold something tight

ARM PAIN - No noticeable change, still hurts if armed grabbed

FATIGUE - Worse since first infusion, often find myself suddenly sleepy

BALANCE WHEN STANDING - Worse since first infusion

BALANCE WHEN WALKING - Worse since first infusion

ABILITY TO WALK UNASSISTED AT HOME - No change, do not use cane in home, but must have light to be able to walk.

ABILITY TO WALK UNASSISTED WHILE SHOPPING - Still using a w-chair

ABILITY TO EXERCISE - Still working with trainer twice a week

ABILITY TO CARRY AN OBJECT LARGER THAN A BREADBOX - Do not feel confident when walking and carrying

ABILITY TO DO HOUSEWORK CONTINUOUSLY FOR AN HOUR - Still can’t clean for longer than 20 minutes before needing to rest

ABILITY TO DRESS,BATH, COMB HAIR, APPLY MAKE UP - No change, I sit while doing these things

ABILITY TO WORK - Still using a w-chair

No one has commented that I am moving better but more than a couple people have commented that I look healthier.  The summer has been unusually hot and my energy problems could be due to that, not the infusion.

[rituximabjourney]

Two Articles From MSAA on Experimental Medications: Rituximab and Ocrelizumab

Experimental Medications                     

Rituxan® (rituximab)

Companies: Genentech and Biogen Idec.

http://www.mymsaa.org/publications/msresearch-update-2013/rituxan/

  Rituxan is a monoclonal antibody (CD20, from mouse tissue) that binds to a receptor on the surface of B cells. These cells are then destroyed and their levels in the circulation are decreased. It is approved for use in the treatment of lymphomas, leukemias, and autoimmune disorders.

A Phase II trial, completed in 2006, examined the effect of a single course of Rituxan treatment in RRMS, with two infusions of 1,000 mg each, administered two weeks apart. At 24 and 48 weeks, the number of active lesions was reduced by 91 percent and relapses were reduced by 58 percent.

The drug was also tested in a study of 30 people with RRMS who had experienced continued clinical activity despite treatment with one of the approved disease-modifying therapies. Participants received two doses of Rituxan, two weeks apart, while continuing to take their usual medication. Results showed gadolinium-enhancing lesions were reduced after treatment with Rituxan: 74 percent of post-treatment MRI scans were free of gadolinium-enhancing activity as compared with 26 percent free of gadolinium-enhancing activity at baseline. There was an 88-percent reduction in the average number of these lesions.

A Phase I/II double-blind study of 80 people with low-inflammatory SPMS, sponsored by the National Institute of Neurologic Diseases and Stroke, is testing Rituximab versus placebo (RIVITaLISe). The study is recruiting participants24 and is expected to run until 2016. The primary outcome measure will be the progression of brain atrophy after two years of treatment, unless predetermined analysis shows that the secondary outcome measures of MRI and clinical assessment are more reliable measures of effectiveness than brain atrophy.

Serious adverse events have been reported in Rituxan-treated patients with other diseases, including Progressive Multifocal Leukoencephalopathy (PML), the same viral infection of the brain that has been seen with Tysabri. While no PML has been diagnosed in MS patients taking Rituxan, the numbers of MS patients treated with Rituxan is relatively small to date.

Rituxan is not likely to be further developed for FDA approval. However, next-generation anti-CD20 monoclonal antibodies have been developed to build on the encouraging data from Rituxan's MS studies, including ocrelizumab, as discussed in the following entry.

Experimental Medications

Ocrelizumab

Companies: Genentech and Roche Pharma AG

Administered via intravenous infusion

Ocrelizumab is being studied in RRMS and in primary-progressive MS (PPMS)

Like Rituxan, this drug is an anti-CD20 monoclonal antibody. It has the potential advantage of being a more humanized antibody than Rituxan. As noted in the introduction to this section, humanized monoclonal antibodies are antibodies from non-human species whose protein sequences have been modified to increase their similarity to antibodies produced naturally in humans. "More humanized" refers to a protein sequence that is more similar to antibodies produced in humans, compared to another humanized monoclonal antibody (Rituxan in this instance).

In a Phase II study of ocrelizumab25 in 220 patients with RRMS, reductions in the total number of brain lesions detected by MRI scans (the primary endpoint of the study) were highly significant at 96 percent for 2,000-mg ocrelizumab and 89 percent for 600 mg compared to placebo. The annualized relapse rate was significantly lower versus placebo at week 24, with a reduction of 73 percent for ocrelizumab 2,000 mg, and 80 percent for ocrelizumab 600 mg. Ocrelizumab's effectiveness was maintained through week 72 (about two weeks less than one year and five months); the proportion of relapse-free patients at week 72 was 84 percent for the 600-mg group, and 82 percent for the 2,000-mg ocrelizumab group.

Infusion-related symptoms, which were generally mild to moderate, were seen in the ocrelizumab-treated groups. The number of serious adverse events was small and similar among the groups. However, one patient in the ocrelizumab 2,000-mg group died of a systemic inflammatory response of unknown etiology (e.g., the reason why this response occurred is not known). Although Phase III trials in rheumatoid arthritis had significant rates of serious and opportunistic infections, none were identified in this trial of 220 MS patients. Please note that the number of MS patients studied in this Phase II trial is small in comparison to the number of rheumatoid arthritis patients studied in the larger Phase III studies that have already been completed.

Several Phase III trials of ocrelizumab are now underway. OPERA I26 and II27 are comparing ocrelizumab (600 mg, as above) to Rebif (44 mcg of interferon beta-1a given via subcutaneous injection three times per week) in RRMS and plan to enroll approximately 800 patients in each study. These trials are anticipated to run through mid-2015. The primary outcome measure is annualized relapse rate; secondary measures include time to onset of sustained disability progression, the proportion of relapse-free patients, MRI measures of disease activity, and change in Multiple Sclerosis Functional Composite (MSFC) Scale.

In addition, because subgroup analysis of Rituxan in the OLYMPUS study suggested a benefit to younger patients and those with gadolinium-enhancing lesions, ocrelizumab is also being studied in primary-progressive MS (PPMS). The Phase III ORATORIO28 safety and efficacy study of ocrelizumab in 630 patients with PPMS is currently recruiting participants. Patients will receive either ocrelizumab (300 mg given intravenously in two infusions separated by 14 days in each treatment cycle) or placebo. The study is scheduled to run through late 2017. The primary outcome measure is time to onset of sustained disability progression (for at least 12 weeks); secondary outcome measures include the time to sustained disability progression (for at least 24 weeks), change in the total volume of T2 lesions (as seen on MRI), as well as safety, tolerability, and the incidence of adverse events.

[rituximabjourney]

Back to Work

A week has past since my second dose of Rituxan and I am back to work.  The temps are still in the 90s and 100s so of course I feel like yuk and I am weak but the kids at school make me feel so loved.  We aren't suppose to hug the kids but they still hug me and make my day. 

Things at work are in a flux.  They hired more teachers and after 5 years I have finally lost my classroom.  Aides don't normally have classrooms so I have been blessed having one for so long.  The district will be bringing in 3 portables and I am told one will be for me and this time I will share the space with another aide.

A week after the infusion, the bloating has gone down but I do not feel any stronger.  Now I am not used to being outside in the heat so I am needing to adjust to my yard duties so feeling weak may have nothing to do with the infusion.  My balance still stinks but my mood, my outlook, is very positive, so the Rituxan is not feeding my depression.  No dark thoughts at all.  That's a positive.

I am taking Cranberry supplements nightly to try to cut the chance of me getting a bladder infection. I do not know what if anything I can do to reduce my chance of getting shingles.  I have purchased all the supplies and tools to provide to my manicurist so to avoid fungal and yeast infections.  I'll let you know if the precautions don't work.

[rituximabjourney]

Infusion Number 1.5

It has been two weeks and now I have had my second infusion of the first round. It is Friday.

My memory let me down and I did not do the prep of Pepcid when I got up  in the morning and that caused a little problem for the infusion and they thought about rescheduling me.  I knew I was forgetting something but I was distracted by my son who had his wisdom teeth removed on Thursday and is having a rough time with pain, swelling and nausea.

It seems there is a national shortage of Pepcid in the infusion form and the pharmacist wanted to hold what she had for the cancer patients.  She decided to let me have a dose but wanted me to know why in the future it is important that I take the meds at home.  She also asked me to take Zyrtec at home to replace the Benadryl infusion, this will shorten the time I am in the chair by a couple of hours.  Sounds good.

Everything started at 8 A.M.  I had a different RN for the infusion this time, her name was Molly.  I was feeling short of breath, I think because our air quality is so bad because of smoke from the wild fires to the north.  She was nice and brought me a fan when I mentioned the I have found a fan helps at home. 

She was very nice but not as talkative as Roger who was my attending RN last time. Roger was there and said hi.  I watched and listened to him as he assisted his cancer patients.  He has a gentle manner and seems to be a caring soul. She is also very attentive and I noticed that she spoke to all the patients even though they were not on her care list. 

When I got the methylpredisone drip I noticed the odd taste returning to my mouth that I complained about last time. I brought grapefruit juice to see if it would help mask the taste since it is acidic and my food did taste better this time so I guess it helped.

The procedure went as it did last time and I slept a lot of the hours away.  My girl friends kept texting me to let me know they were thinking of me.  I sent out a group text at lunchtime saying that I was feeling like it was a good day for chocolate.  One of my girlfriends is a florist and she made up a cute little basket of daisies (my favorite flower) and brought it to me at the infusion center with two big bags of M&Ms!  Her grand daughter added a butterfly. I am so lucky, I have the best girlfriends.

At home I observe that my feet aren't burning again like last time.  My shin which as been sensitive to the touch feels normal. I suspect that the burning will return Saturday night if I follow what happen two weeks ago.

By 10 P.M. my legs, feet and hands had swelled up and the scale said I was weighing 3 to 4 more pounds than I did in the morning.  Again I didn't sleep last night, so I spent time reading articles on Rituxan as a MS treatment.  I'll share what I learned in a later post.

I'm still looking for others to share on this blog because I can't find anyone with MS talking about this treatment.  From what I have been reading I don't think there are many of us out there because the treatment is so new.  We can help by sharing with each other.

[rituximabjourney]

Expanded Disability Status Scale

As of August 2014, my EDSS is 6.0.  I am aiming toward 5.0.  It helps to have a personal goal.

Second half of first round is tomorrow.

EXPANDED DISABILITY STATUS SCALE

[rituximabjourney]

Study Hints of Rituximab MS Benefit

FYI . . . . .

Study Hints of Rituximab MS Benefit

Published: Jun 3, 2013 | Updated: Jun 6, 2013

By  John Gever , Deputy Managing Editor, MedPage Today

Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner  http://www.medpagetoday.com/MeetingCoverage/CMSC-ACTRIMS/39569

Action Points

Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Note that this retrospective study suggested that, among patients with secondary-progressive MS, the addition of rituximab was associated with stabilization of disease.

Be aware that the study was small (just 25 patients) and lacked a control group.

  ORLANDO -- Most patients receiving off-label rituximab (Rituxan) for secondary progressive multiple sclerosis either improved or showed little further progression, according to results from a small retrospective study.

Among 25 patients with secondary progressive MS treated with rituximab, nine showed decreases in disability and 12 appeared to stabilize after receiving at least three cycles of rituximab given every 6 months, said Christopher Perrone, a fourth-year medical student at the University of Massachusetts Medical School in Worcester, Mass.

Compared with patients' previous rates of disability progression before starting rituximab, as measured with the Expanded Disability Status Scale (EDSS), further progression appeared to slow markedly while on the drug, Perrone said at the joint meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

By the third cycle of rituximab treatment, mean EDSS scores were almost exactly equal to the mean 1 year before starting treatment.

Rituximab is an anti-CD20 monoclonal antibody drug approved for certain hematologic malignancies and for rheumatoid arthritis. It is sometimes used off-label in MS, but its effectiveness and optimal role have never been firmly established.

Perrone told MedPage Today that some patients with secondary progressive MS have been receiving the drug at his institution when they have exhausted other options. He noted that mitoxantrone is FDA-approved for secondary progressive MS but, like other immunosuppressant drugs used in the disorder, it is relatively toxic.

For the current study, he and colleagues at UMass examined records of 30 patients who had received rituximab after failing conventional MS drugs including interferon-beta and glatiramer acetate (Copaxone) as well other therapies such as methotrexate, cyclophosphamide, mycophenolate mofetil, and corticosteroids. Such agents are treatments of last resort in many other autoimmune diseases.

Some patients considered for the study had received natalizumab, but they did not meet all the study's inclusion criteria and were therefore left out, Perrone said.

Patients in the cohort had shown significant declines in functional ability during the 2 years prior to starting rituximab, gaining about 0.5 EDSS points per year (increased EDSS scores reflect growing disability).

But after the first cycle of rituximab -- 1-g intravenous infusions 2 weeks apart -- the mean increase in EDSS over the following 6 months was less that 0.1 point. Mean progression after the second cycles was 0.05 points, Perrone reported.

By the time of the third cycle, analysis of each patient's pretreatment rate of disability progression suggested that the cohort's mean EDSS score would have reached about 6.2. Instead, it was about 5.6.

Perrone told MedPage Today that patients with very high EDSS scores (6 and above) before starting rituximab tended to show stabilization of disability, whereas most of those with lower baseline EDSS values either failed to respond at all or had marked improvements in functional ability.

MRI scans showed no changes in disease activity while on treatment, except for one patient showing a new non-enhancing lesion.

Adverse effects were those typically seen with rituximab -- mostly infusion-related reactions, urinary tract infections (to which MS patients are especially prone irrespective of treatment), and rashes.

Lack of a control group and the relatively short follow-up were notable limitations to the analysis.

Jerry Wolinsky, MD, a prominent MS specialist at the University of Texas Health Science Center in Houston, said that the history of treatments attempted in progressive forms of MS has been mostly marked by failure.

But he argued that, to a large extent, that may be because the demarcation between relapsing and progressive MS remains fuzzy, and because EDSS -- the most common tool for evaluating disability -- is "a horrible measure."

He suggested that a closer look at some of those previous data indicate that some treatments -- including rituximab, which was evaluated in a placebo-controlled trial reported in 2008 -- may have been at least partly effective in slowing disability progression.

Wolinsky said two large, well-designed trials now underway would help determine whether drugs known to be effective against MS relapses would also help in secondary progressive disease. One involves natalizumab (Tysabri) and the other is testing fingolimod (Gilenya); each involves about 900 patients and includes placebo control.

[rituximabjourney]

One Week After 1st Dose

I was wondering how I would feel after receiving Rituxan.  I did worry about the heart issues and I worried about getting sick to my stomach.  Neither of those two things happened but I do feel different, but not in an improvement way. 

My balance, which was problematic already, is worse. I have experienced real burning pain on my left shin and even though I am back on the Ritalin I really feel weak.

Previously only my feet "burned" but now my right shin bone is super sensitive and touching it hurts a little more than a bit.  I have had numbness below the knee for years.  I wonder if I am feeling a return of sensation or am I experiencing an unrelated pseudo-exacerbation  because it has been over 100 degrees for quite a few days.

The summer of 2013 was a great summer for me physically.  I felt better than I had in years, I had more energy even though it was summertime when I usually decline.  When I walked into the school where I work, many people commented about how much my walking had improved.  That made me wonder if my better outcome was due to the drug study drug (Tysabri) or due to me being on no drugs (placebo). 

This summer has not been so kind.  Heat came earlier this year and I felt awful the last two months of the drug study.  I wasn't even wanting to finish the walking test that was part of the study monitoring as I rolled out of the study.  I blamed the heat, I still do.  I don't think I am going to be able to judge any physical improvement until these 100 degree plus days are gone.

My second infusion of Rituxan is next Friday. 

If your interested I found a couple good articles that I have saved for future reference:

Paroxysmal Symptoms of Multiple Sclerosis: They Come and They Go  http://www.unitedspinal.org/msscene/2008/11/18/paroxysmal-symptoms-of-multiple-sclerosis-they-come-and-they-go/

Kidney Stones  http://www.nytimes.com/health/guides/disease/kidney-stones/prevention.html  (I haven't had stones but many of the drugs I take can increase the chance of forming stones, so I'm trying to be preventive)

[rituximabjourney]

Aftermath

Okay I was right, I hardly slept last night.  Maybe an hour or two.  Something interesting though, my legs and my feet did not hurt at all last night or today.  I had energy today and I did some housework and grocery shopping.  I am guessing that the energy was from the methylprednisone. 

Tonight the burning has returned to my feet and my legs and feet have swollen up and the legs feel like they weigh 100 pounds each.  It is hard to lift them. 

[rituximabjourney]

Infusion Number 1

THE PATH TO RITUXAN

I am a 58 year old female with relapsing remitting MS with secondary progressive (RRSP).  I first tried an interferon drug for less than a year and my bone marrow couldn't tolerate it.  I next tried Copaxone and I took this drug for 5 years.  I continued to have relapses and my recoveries started to show less and less recovery.  I was re-diagnosed with secondary progressive and my neurologist and insurance company connected me with an MS specialist who had patients in a drug trial for getting FDA approval for Tysabri for the treatment of  RRSP.

I have the John Cunningham virus (JCV) antibodies so by participating in the trial I had a 1 in 100 chance of developing progressive multifocal leukoencephalopathy (PML) after 2 years on the drug.  My new neurologist wanted me to leave the trial after 15 months for this reason. 

She recommended I try the Rituxan for many good reasons.  Yes there is a risk of PML but I read those odds are 1 in 25,000.  I chose this treatment course because there was no other treatment my insurance would cover at this time and if it is possible I want to dance with my husband again.

In the last eight years I have slowly digressed from walking without a cane to relying on a wheelchair more and more.  I can't shop without a motor cart, I can't clean my home for longer than 20 minutes before having to sit down for an hour or more. I have developed edema so I have changed my diet.  In one summer I put on 15 pounds that I am fighting to lose.

I do work out with a trainer twice a week.  This has made a real difference in my strength and balance but not my endurance.  Will Rituxan give me back some endurance? I don't know because I couldn't find people's stories of physical improvement after taking Rituxan.  This is why I hope others will regularly share about what it is like to be on Rituxan and if they are physically improving.

THE INFUSION--8 A.M.

I was instructed to eat a normal breakfast and take 40 mg of Pepcid an hour and a half before my appointment.  I was given a cocktail of drugs by infusion and pills to counter the side effect of the Rituxan.  They gave me 975mg of Tylenol (not sure why), and an infusion of 50 mg of Benadryl (for itching), 500 mg of methylprednisone (Corticosteroid, I hope I can sleep tonight -- probably won't because the Benadryl caused me to sleep most of the 7 hours) and 1000 mg Rituximab.

I started to feel the Benadryl in my eyes which is the same place I feel alcohol when I have drunken too much.  After a few minutes I found it very difficult to stay awake.  I did wake up each time the infusion counter went off but fell back to sleep very easily. At about 10 A.M. I noticed that my mid-distance eyesight was off and I was seeing a "shadow" of everything I looked at. This went away shortly after the infusion stopped.

The worse side effect was a metallic taste in my mouth that made everything taste like rubbing alcohol.  I ate my Peta chips mid-morning to try to change what I was tasting but to no use.  The RN said the cause was probably the corticosteroid. I ate my lunch of a sandwich which really tasted different and the apple slices weren't good either.  I'm actually glad I kept falling a sleep so that I wasn't aware of the taste in my mouth.

I went home and ate a couple of chicken legs from last night because I was hungry.  I think one of the drugs made me hungry because I did eat like normal while at the cancer center.

LATE NIGHT -- 12:00 A.M.

Yep I can't sleep.  I intentionally haven't taken a steroid drug because I don't like how it made me feel.  One problem was I didn't sleep for 3 days after a 3 day steroid treatment. 

I have developed no other symptoms, and I am not any hungrier than normal.