A Clinical Trial – Patient Journey – Part II

I mentioned at the end of A Clinical Trial – Patient Journey – Part I that I had originally planned not to share my experience until after the placebo arm was over. On reflection, I realised that would in fact be unintentionally biased reporting, because events during, and the experience of, that first six months, when I may or may not be on the active intervention, are valid when discussing clinical trials from a patient perspective.

I had convinced myself I would get the placebo. I do not have a history of winning at chance! The lottery? Yeah, nah. Raffles? Not a hope. Scratchies (are they still a thing)? Never! I did once win $100 in a work event of some sort, but that is hardly indicative of a great winning streak. Psychologically, it is easier to plan on having a further toughish six months than be disappointed if nothing happens. Makes sense, I think!

In Part I, I also mentioned I thought I may get an early indication based on any skin improvement. This graph is from psoriasis clinical trials.

Source: http://www.medicines.org.au/files/vepskyri.pdf

As can be seen from the above, results in the skin trials were seen very quickly. Although the trial in which I am participating is for the arthritic condition, the skin condition will also be treated.

Let’s pick up where we left off, at the baseline visit.

Baseline

After dealing with all the paperwork, doctor consultation, having bloods and urine taken, temperature and blood pressure checked, joint and enthesitis assessment and answering a lengthy quality of life type questionnaire on an iPad, it was time for the injections. I remember watching it go in (yes, I watch injections, apologies to squeamish readers) and thinking, “There’s my saline solution dose for the day”. One into the abdomen, one into the thigh.

From November 2018, I had been having UV B light therapy for the psoriasis. It really works well, but one of the criteria of the trial is no light therapy. Makes sense – the aim is to test the efficacy of the drug and that would be most difficult if certain other therapies (see explanatory comment below) were being employed at the same time. So I had to stop light therapy a specific period of time prior to the baseline visit.

The following two photos I took July 6. While with UV B and methotrexate it had reduced dramatically, once off both those therapies the skin had flared again. My baseline visit was July 17. I’d stopped the UV B therapy a little earlier than I otherwise would have, because I’d stopped in preparation for one trial, then ended up on the sister trial with a later start date.

These photos are embarrassing to share, nor are they anything like “clinical quality” as I just snapped them with my phone, but they are more meaningful that quoting percentages. If my articles are to be useful to readers, I have to be prepared to drop the mask of normality so many of us wear a lot of the time. I wanted my own baseline for comparison. We forget how things looked, over time: I wanted to be able to look at my skin further down the line on the trial and be able to see (or not see) any change. As this trial is for psoriatic arthritis, not psoriasis, no photos are part of the trial documentation.

The image on the left is a patch on my leg. The image on the right is my upper chest, just below the collar bone. You can see older images of my arm on “I am Medication Free! For Now, Anyway…

The skin makes swimming and hydrotherapy embarrassing. Rightly or wrongly, I worry other swimmers are going to think I’m contagious. It just looks…..horrid. Worth mentioning, perhaps, this sort of skin involvement is new to me – when I say new, I mean I went through MANY years of my life with the odd tiny patch which would disappear, or absolutely none. I am not used to this.

I’ve shared this swollen foot photo before, this was February, just as DMARD number two washed out of my system. This is the psoriatic arthritis aspect. The right second toe is clearly also swollen – dactylitis. Yes, you may indeed compliment me on my choice of polish!

The joint and enthesitis assessment is quite lengthy because it involves an independent assessor testing the many finger and toe joints as well as, jaw (TMJ), feet, elbows, shoulders, sternum, knees and hips (SIJ). It seems as if, if you have a joint, they will assess it! I never think of my toes being sore, aside from the big toes, yet it is surprising just how sore they are when a relatively light test pressure is applied. I knew my thumbs were sore, but all those toe joints: ouch, ouch, ouch.  My fingers, aside from the thumbs, are OK. Even the thumbs are not bad – the soreness doesn’t stop me doing anything AT THIS TIME: however my concern is disease progression. I want, if at all possible, to stop progression.

The assessor also looks at and records the percentage of the body showing skin involvement.

At the point of the above photo, I could not fit my runners on at all – that makes exercise difficult as the gym frown on bare feet for safety reasons. The swelling had reduced a bit by July, but I was still struggling to wear runners for any length of time. The assessor, using a clinical approach rather than my layperson’s visual assessment, flagged many of my toe joints as swollen as well as sore. We get used to looking at our own bits and pieces and over time the abnormal can start to look normal.

Which injections you get is controlled by a mysterious person far, far away. To that mysterious person I am just a number. My co-ordinator emails the mysterious person, who I suspect at baseline tosses a coin to decide which arm I’m in: active or placebo. Of course I am joking – it is likely much more scientific than that. Now I’m curious – I must ask next visit!

An email comes back advising which two numbered boxes are to be used for my participant number. I wanted to keep the boxes as souvenirs (main photo) but they have to be kept for the trial auditors to check I was given what I was supposed to be given.

None of us, the investigator, or my co-ordinator, or I know what is in those syringes. It is a 50/50 lottery at baseline.

After the injections the trial participant (i.e. me) sits around for two hours in case of an adverse reaction.

Take a book or iPad or Kindle with you is my advice! You may have another participant, of your trial or another trial, to chat to or you may be sitting alone. Very comfy chairs, nice throw rug for colder days, but essentially a pretty boring two hours.

Then time to go home.

Please, PLEASE bear in mind that even if you were on the exact same trial as I am on, you may have a completely different experience to my experience. Your disease would not be at the exact same stage as mine, you may have more or less joints affected, you may have more or less skin involvement, you may suffer more or less fatigue than I do. So many variables. What I write is my specific experience. Your experience may be similar, or not.

The next stage in the loading dose. This happens four weeks after the baseline injections.

I know, I know, you want to know where I am on that graph! Can I fit my runners on now? Well, I gave the runner answer away in a recent article if you are paying attention. Be patient, all will be revealed in good time. I had to wait and see!

Explanation re Concurrent Therapies

Although light therapy is not allowed, participants may stay on up to two DMARDs while on the trial. After all, if the participant is in the placebo arm, if no concurrent therapies were allowed, those participants would effectively be receiving no treatment at all for six months. Each clinical trial will have restrictions specific to that trial.

I am also restricted in what other medications I can take, such as pain medications. Given I rarely take any pain meds (exercise is my pain management), that didn’t worry me. I can’t change my dietary supplements, although I can stay on the ones I started on e.g. Vitamin D as ordered by my endocrinologist, fish oil as recommended by my sports physician. There are rules around surgery during the trial.

These are all considerations when deciding whether to participate in a clinical trial.

A Clinical Trial – Patient Journey – Part I

Background

After discovering last November (2018) that my second DMARD (disease-modifying antirheumatic drug) had to be retired from my treatment regime, I did two things. I tried going medication free. I also started researching drug trials. If being medication free didn’t work, what was going to be my next step? What choices did I have that might be outside the standard treatment pathway?

Why research drug trials in particular? The first DMARD I was prescribed was developed in the 1930s. The second was introduced in 1955, originally to treat malaria but was later found to have immunomodulatory properties. These drugs are as old or older than I – surely modern medical science had something better by now? Something I wouldn’t have reactions to?

Well, yes, there are newer drugs available. Biologics are available on the PBS (Pharmaceutical Benefits Scheme) – IF the patient qualifies. That qualification bar can be high. As a example, this link to the PBS has the qualification requirements for one biologic that may be used to treat psoriatic arthritis. Click on the red “Authority Required” link to see the qualification requirements. When would I qualify? When I was 80? Not really a very positive thought for me. Yes, a private script can be given, but at $1,049.69 for four injection pens that is a little outside my price range long-term. And that is one of the cheaper ones. $40.30 with PBS subsidy. The schedule is usually inject once a week, so that is a monthly cost.

After much researching I found a drug trial that appealed to me. I don’t know who thinks up drug names, but this is risankizumab. Before I learnt how to say it, I referred to it as the “Kazakhstan drug! I had researched the drug extensively, then looked for trials in Australia. The drug had already been approved in some jurisdictions to treat the skin condition psoriasis, so there was plenty of information available. On July 23, 2019 it was announced this drug received TGA (Therapeutic Goods Administration) approval for use in Australia, but is not yet on the PBS.  Published results from those clinical trials were very informative and positive.

The trial in which I am a participant is to assess the efficacy for psoriatic arthritis.

So I had found a drug trial I was interested in for a drug that looked very promising.

What Was I Looking For?

At this point you may be asking what was I looking for by considering doing a drug trial. As odd as this may sound, I was looking for treatment stability. I am now on my fourth DMARD. Each one has not been the right medication for me. As noted above, some of these were not the newest drugs around. Plus there was this encouraging line on the patient information sheet of one: “It is not clear how [drug X] works.” Or this one: “It is not clear how [drug Y] works in inflammatory conditions; however it is thought to have an action on the immune system.”

There is my personality type to take into consideration. I’m one of those annoying yellow quadrant HBDI people – we are the experimental thinkers. This might make me a radical patient, I suspect! It means I’m always looking “outside the box”.

I’d also had the experience of having a Synvisc injection when it was very new – that experience had been extremely positive for me. Trying new stuff is not something that scares me in the slightest.

I have faith in medical science. No, we don’t always get it right, thalidomide being the classic example as I have discussed before. I don’t seem to qualify for the biologics currently on the PBS, yet I was desperate to at least try a medication younger than myself. A medication where the therapeutic action was actually known.

I wanted something that worked without the myriad of side effects I’d experienced to date. I was also looking for a medication that might address the fatigue that goes hand-in-hand with many chronic conditions, including psoriatic arthritis.

A Third and Fourth DMARD

There was an event that drove me even more in the direction of being involved in a drug trial. In March this year, while I was still mulling over the prospect of being a lab rat, I suffered an adverse reaction to my third DMARD. I was prescribed a fourth DMARD. It seemed if there was a reaction to be had from these DMARDs, I was unfortunately a person who was going to react. By this stage I had lost faith in DMARDs as a treatment for me. I must stress, they work perfectly well for many, many people. I’m just not one of those people, it seems. One of the DMARDs had worked wonderfully for the arthritis, but ruined my skin, for example. There was something with each of them.

Again, I stress, all these were the standard treatment pathway. I wasn’t being “mistreated” in any way.

Next Steps

I discussed the proposal with my GP, my dermatologist, my urologist and my pharmacist. All four were very supportive. I have since also brought my gastroenterologist up to speed and he is also supportive. I must make clear I was not asking them from a rheumatological perspective of course, I was seeking any concerns they may have for me in their field of speciality and/or any concerns they may have about MABs in general.

I signed up and waited for the screening appointment. While waiting I bit the bullet and got a second opinion. This rheumatologist was also supportive of my desire to do the trial. Disclosure time. Through sheer coincidence this professor happens to be involved with the drug trial. My GP had written the referral well before I’d found the trial I was interested in. My GP had not even known I was researching drug trials, I had never mentioned it. The fact there was a connection was serendipitous.

Screening

My initial screening appointment was on my birthday! That was in June. So. Much. Blood! They do take a lot of tubes of blood, let me tell you. At least for this trial. I failed the first screening. Probably because I’d been taking prednisolone to try to control the inflammation while DMARD four ramped into gear, my CRP (C-reactive protein) had dropped 0.15 below the cut-off. A month earlier it had been way over. Luckily there was a sister trial with different patient qualification criteria and those criteria I did meet. That meant a second screening appointment. That took place in July. Of course, at this later screening my CRP was back up again, well over the cut-off for the first trial, but the rules are the rules. I am on the sister trial.

You are weighed, height measured, vitals taken, blood tested, joint and enthesitis assessments are done. The skin is assessed. There is paperwork, lots of paperwork. A medical history is taken (I took in a typed history from birth to now). A consultation with a site doctor. All up the screening process takes about two hours.

When I cite visit durations, these are for this particular trial. Other trials for other medications may be longer or shorter.

Active or Placebo?

This is a double blind clinical trial. Those wanting further information on clinical trial protocols in Australia can read this link at Australian Clinical Trials. Yes, there is a placebo arm. While the trial goes for four years, the placebo arm only goes for six months, after that all participants are on the active intervention. My rationale was six months of placebo could not be more difficult than the last six months I’d been through and I would only have to manage for six months if I lost the 50/50 lottery. I had nothing to lose.

I also knew that results from the trials for treating the skin condition showed very little placebo effect and that results had been seen quite quickly. I felt I would have a very good indication before the six months was up of whether I was on the placebo or the risankizumab, based on my skin.

Baseline

My Baseline appointment, the appointment where you actually receive the drug or the placebo, also took place in July. This was a much longer appointment. Essentially all the steps of the screening appointment are repeated, plus the injection, plus the patient has to wait for two hours post injection to ensure there is no adverse reaction. The coffee is good.

How is it going?

I was originally not going to write about this until after the six months. The fact I am writing earlier should be a slight hint. This will be a series as there is way too much information for one article! Tune in later in the week for Part II!

I Am Medication Free! For Now, Anyway……..

Right now I am medication free! No, I have not forsaken the wonders of modern medicine in any way shape or form, but in careful consultation with my rheumatologist I am taking nothing at the moment. How long this will be the case, I am unsure: we will reassess in February. If anything goes belly up, I’ll just make a phone call.

NEVER CHANGE YOUR MEDICATIONS WITHOUT YOUR DOCTOR’S APPROVAL.

Why is this happening? The medication I was on, my second inflammatory arthritis medication, was GREAT for the arthritis. However, it is considered not so great for my skin. This is my left arm a couple of days after the biopsies. This is the worst patch, always has been the problem area. Ignore the scar circled in black – that was the result of having a run-in, literally, with a broken fire extinguisher. The area circled in green is one of the biopsy sites.

Why is my suture not covered? Well, the steri strips started to come off, so I soaked them off. I can not use bandaids of any sort any more, my skin is so fragile – I remove them and the skin comes with them. Rather nasty, so I just don’t go there. It is bandages after bllod tests these days.

About two years ago we investigated my skin and it was then diagnosed as photosensitive eczema. It looked a little different back then. This November I have a completely different diagnosis. This does not mean the original diagnosis was incorrect – things change. In 2016 I was on different medications. Around the time of that first diagnosis I changed my arthritis medication and early this year (2018) I ceased taking medication for my hyperthyroid, having undergone radioactive iodine treatment. So a few changes in the two years.

My skin diagnosis now is atypical psoriasis, believed to be exacerbated (considerably) by my arthritis medication. My dermatologist discussed the matter with my rheumatologist and off the medication it is! I am starting UV B light therapy in the new year – can’t wait! I say atypical because it looks more like subacute cutaneous lupus erythematosus (SCLE) (per dermatologist) than psoriasis, but the biopsies, thankfully, told a different story.

My nails, which usually readers never see due to my passion for polish, look like this. Not all the time, it comes and goes, but the little fingers are particularly unhappy at the moment.

The next medication in line for me, agreed to by my dermatologist, rheumatologist and gastroenterologist, is methotrexate. By the time I saw my rheumatologist, I had been medication-free for a month and I don’t feel too bad at all. I asked about the possibility of seeing how I go without any medication. Other medical professionals are investigating some other symptoms I’m experiencing, some of my blood tests have been a bit erratic – it might be easier to isolate a cause if I’m medication free. That consideration aside, the less medication the better makes me happy. Methotrexate only takes four weeks to “kick in” and I’m certainly not going to be a martyr about it – if I feel I’m going downhill, I’ll be in my rheumatologist’s office very quick smart. I have backup medications in case I flare.

As I have to change medication anyway, it is an opportune time to try and see what happens. My arthritis related blood tests have improved considerably since late 2014 when I was diagnosed.

So how am I finding it? My feet have niggled at me a few times, both my knees are slightly grumpy at night if I walk too much during the day, the base of my thumbs hurt a little bit with certain grip actions (think holding my drink bottle to unscrew the top). If I have a really busy day I do stiffen up at night – but then that is not exactly new, I don’t think it has gotten worse – it is also more likely related to the degenerative changes in my lumbar spine than the arthritis. Other than that, I can’t complain. I swam 1,100 metres today, the first time I’ve managed a swim session over 1,000 metres for quite some time. I did 40 minutes strength training yesterday, my quad strength is actually improving. I did 9,000 steps (accidentally) on Thursday with no ill effects.

My biggest concern is my fatigue/lethargy may return. For me, that was a major problem. Settling the thyroid helped, of course. Now my bloods are indicating my parathyroid is not behaving – endocrinologist appointment in January to try to get to the bottom of that.

The BEST part is I can go out in the sun – sensibly, of course. I’ve spent two years avoiding any sunlight because of my skin, slathering sun cream from head to toe: slip, slop, slapping to within an inch of my life. Yes, I still have to be Sun Smart, but at least I can be normally Sun Smart now instead of paranoid! I also feel better psychologically: I felt as if I was a constant Seasonal Affective Disorder patient.

I don’t know if I will stay free of medication for the arthritis. I see this as an experiment. I do seem to be susceptible to the side effects of medications so if I can stay as healthy as I am now, I’ll be happy. Any deterioration, I’ll be in my rheumatologist’s office. It takes a while for the drug to wash out of one’s system, so I won’t really know for three months – I’m only a third of the way through.

I am very grateful to my specialists for allowing me to try this. It would not be an ideal option for a lot of patients, I know. I am certainly not recommending what I am doing and would definitely NOT be doing it without having discussed all the pros and cons with my guardian angel doctors. I am monitoring myself carefully.

The physical fitness and strength I’ve slowly spent four years building back up has certainly helped me manage my condition so far, but no, there is no guarantee by itself it is enough.

We shall see – wish me luck!