Table 1. Demographic and MS-related characteristics of participants
Characteristic
|
N (%)
|
Females
|
35 (70)
|
Age (mean, range)
|
44.4 (21 – 61)
|
Highest professional qualification
|
|
Still in vocational training
|
1 (2)
|
No professional qualification
|
2 (4)
|
Vocational education
|
27 (54)
|
Bachelor’s degree
|
4 (8)
|
Master’s degree, Diploma, state examination
|
14 (28)
|
Doctorate
|
2 (4)
|
MS type
|
|
RRMS
|
44 (88)
|
SPMS
|
6 (12)
|
Years with MS since diagnosis (mean, range)
|
13.4 (2 – 33)
|
Patient determined disease steps (PDDS) (mean, range)
|
2.7 (0 – 7)
|
Current DMT use
|
39 (78)
|
History of DMT use (number of different DMTs so far)
|
|
0
|
3 (6)
|
1
|
3 (6)
|
2
|
11 (22)
|
3
|
13 (26)
|
4
|
12 (24)
|
> 5
|
8 (16)
|
Experience with DMTs
|
|
Glatiramer acetate
|
16 (32)
|
Interferon-beta
|
33 (66)
|
Dimethyl fumarate
|
15 (30)
|
Teriflunomid
|
10 (20)
|
Alemtuzumab
|
7 (14)
|
Daclizumab
|
4 (8)
|
Fingolimode
|
17 (34)
|
Natalizumab
|
17 (34)
|
Cladribine
|
3 (6)
|
Ocrelizumab
|
8 (16)
|
Mitoxantrone
|
3 (6)
|
In this study, 50 pwMS were interviewed. Interviews lasted between 20 and 97 minutes (mean = 45.6). 22 interviews took place in Northern Germany, 23 in the South, and 5 in the East. Regarding our sampling strategy to gather experiences from at least 3 patients for each DMT, recruitment was successful (Table 1). Our analysis examined experiences of pwMS with DMTs and resulted in the identification of the themes shown in Figure 1. All exemplary quotes which correspond to the themes can be found in Additional file 2.
Starting a DMT
Decision-making process
All participants had been engaged in decisions about DMTs. 47 had experiences with at least one DMT. When we say “starting a DMT”, we do not refer solely to the first-time treatment with a DMT, but also to starting any new DMT. Different intercorrelated factors influenced the decision-making process when starting treatment with DMT.
The pwMS’ autonomy preference in decision-making differed, ranging from a physician-dominated, a shared, to a patient-dominated approach. PwMS who were faced with a decision right after diagnosis, reported a high level of helplessness, shock and trauma, and a lack of biomedical knowledge. Some pwMS, however, experienced a sense of relief that their symptoms now could be explained. Other felt powerless and overwhelmed by the amount of new information. In this situation, the physician’s recommendation had a high impact on the treatment decision: “Unfortunately, you can quickly feel pushed into starting a therapy, that’s how I’d put it, because you’re immediately made to feel afraid, too. That you might end up in a wheelchair, say, that it will only get worse if you don’t do this. Yes, I felt really rushed into it, and that’s how I started out on therapies.” [pwMS 4]. Some physicians might have the tendency to motivate early treatment through anxiety.
On the other hand, our interviewees told how they were presented with information about a set of options by their physicians and were advised on all options. They used this information as well as other types of information sources, such as internet-platforms and information brochures, to prepare for a decision and informed choice at a follow-up appointment. Interviewees reported that they appreciated having an active role in decision-making. Thereby it was important to take breaks to process the information in order to be able to make a decision. However, there is a fine line as to whether patients see this as participation in decision-making or as being abandoned: “But on the subject of therapy, he says: ‘So, you’re welcome to take these three brochures home, take a look and choose one.’ As an introduction, I thought that no bad thing. Then came the follow-up appointment, as agreed, and it was still: ‘Choose one.’ At that point I felt abandoned, not that he was giving me freedom.” [pwMS 3]. Patient-dominated decisions resulted from high autonomy preference in decision-making and occurred when switching or discontinuing treatment with a DMT.
Different needs of the pwMS turned out to be important factors in decision-making. One need was the desire to delay progression. Out of a sense of urgency pwMS wanted to start DMT immediately: “And I thought, okay, maybe it’s not going to be so bad after all. That was my first relapse. And I’ve plenty of time. But nonetheless I should try to halt the disease course as quickly as I can.” [pwMS 33] – “Yes, of course at that time I was like: ‘Oh, just give me something to stop it getting too bad.’” [pwMS 2]. PwMS had the desire to do something about their situation especially after the diagnosis, take responsibility and start treatment to (re)gain control: “It was really helpful having a therapy, something to actively combat the many fears that come into being at diagnosis time.” [pwMS 32]. Another need was a simple mode of administration of a DMT. If there was a choice between self-injectables, oral medication and infusions at the time of diagnosis, patients preferred oral medication or infusions.
After diagnosis, patients were faced with an evaluation of possible benefits against possible risks of DMTs. When the disease did not considerably influence everyday life, pwMS were encouraged to start with a less effective but low-risk DMT: “Well, with the first-line therapies it was relatively straight-forward, even the word ‘first-line therapy’ isn’t too scary. The side-effects are straightforward […] [DMT B], yes, flu-like symptoms, that’s something you can cope with. […] [DMT H] was definitely a bit more difficult, because of that JC virus [causing opportunistic infection of the central nervous system], I wasn’t that old then, had all sorts of new plans. […] So really my choice was between continuing to suffer relapses and their unforeseeable consequences, or daring this leap.” [pwMS 16].
During the process of starting a DMT, the social environment played a role, too. Firstly, there were the family and partners with whom patients consulted regarding DMTs. Secondly, there were other pwMS whose stories and views our interviewees sought when starting a therapy: “At our MS group […] the consensus was actually: Yes, start a therapy right away. Any therapy is better than no therapy.” [pwMS 33].
Effort in the mode and frequency of administration
PwMS experienced different forms of effort in the mode and frequency of administration in daily life as well as in the emotions and feelings triggered by handling DMTs. DMTs are available as tablets, syringes, or infusions. There were different views on which administration form and procedure was more convenient. For the majority, placing the syringe was a great challenge and many experienced injections as stressful and unpleasant. Some pwMS included their family in the administering of injections. By involving other people in the handling of certain DMTs, these may then be perceived as less amenable, because patients become dependent on other people: “Before that I’d never had to give myself an injection. These are ones you just have to do subcutaneously into the stomach area, and my wife did the first one for me, but then for me it was a bother to ask someone else, so I learnt how to do it myself.” [pwMS 17]. On the contrary, for some pwMS self-injection was unproblematic.
For others, taking oral medications was more relaxed, although there is an increased risk that patients forget to take their pill: “You take the tablets, one in the morning and one in the evening, which some people find tricky. It is easy to forget. That can happen reasonably easily when it is two tablets a day, but you get into the way of it, I do think. So, to begin with, I was always forgetting.” [pwMS 36]. The procedure around taking the pill, e.g. the strict handling instructions can be perceived as a burden. All in all, starting on oral medication was regarded as less intrusive. PwMS wanted a DMT, which does not confront them constantly with the disease. This was seen as the case for oral medication, but also infusions: “The treatment [with DMT E] is in two subsequent years, in the first year you receive five infusions, and in the second year three infusions on three subsequent days, and in between there is no medication and that in itself is very pleasant.” [pwMS 48].
There were pwMS who preferred infusions to oral medications or syringes. Some described the infusion as relaxing and pleasant, because there was no need to think about taking it by themselves. Nevertheless, it makes a difference whether the infusion is monthly or half-yearly. Some patients stated that they felt well looked after in the clinic when integrated in an infusion scheme and during the infusions: “This infusion is supervised throughout. […] So, I felt in really safe hands there.” [pwMS 48]. But there were also pwMS who said that the infusion was stressful, unpleasant, and frightening. Some reported that the infusion gave them the impression of being more sick compared to oral medications, which are perceived as a more common part of everyday life: “The moment I was lying there, whenever I entered, it was like that – yes, I have a serious illness. […] And that was different with the tablets. Because tablets are just much more integrated into the everyday.” [pwMS 34]. The interviewees described diagnostics and other procedures that must be carried out before starting therapy and during the treatment with DMTs – the determination of blood values, vaccinations and magnetic resonance imaging (MRI) scans, for example – as very time-consuming and burdensome. This may have made pwMS even more aware of the potential adverse effects of DMTs.
PwMS developed a routine for the self-management of a DMT: taking the oral medication with breakfast, or taking a warm shower before the injection to avoid haematomas. One patient reported how she takes time off when taking her DMT: “Of course it means a week where the evenings are spent at home, I try to live more tranquilly. And definitely no alcohol that week. But it’s just a week, five evenings. And then it’s done. You take it in the evening. And that’s it, nothing more to it.” [pwMS 34]. Some forms of application were regarded as easily to be integrated into everyday life and others less so, when they had to be taken at a certain interval and in combination with food, for example.
Also, the complexity of handling a DMT in work life needs to be considered. Some DMTs demand a considerable amount of time for the mode of administration or thereafter. So, pwMS might need to take time off. Concerns have been expressed that time-consuming forms of administration may require an outing to the employer: “I just don’t know how anybody with a full-time job who has fixed working hours and who doesn’t want their employer to know, I just don’t know how they do it. […] Perhaps I don’t have to say that it’s MS. But I do at the very least have to tell that I’m going to a doctor. And anyway you get a letter from the doctor as proof. And then any employer can see which [specialist] you’ve been to.” [pwMS 34].
When travelling, it should be considered that some DMTs require cooling and that for injectables a certificate should be carried when traveling by plane, which reduces flexibility: “In my job […] there were a lot of events to fly to. And it was quite an undertaking, getting through security with [DMT B], ensuring it remained well-cooled etc. The same with the needles going through security, quite a palaver too.” [pwMS 33]. Patients explained that they must prepare their vacation further in advance, especially when taking DMTs as injectables.
Success and failure of a DMT
For some pwMS, DMTs have had no effect on the relapse rate. Others reported reductions in relapse rates. Some pwMS repeatedly reported (supposed) improvements in MS symptoms: “Well, the advantage with [DMT H] was that symptoms that were residual from the last relapse, such as not being able to run, for example, disappeared entirely […]. And that’s when I actually completely forgot that I had the illness.”– “After my third infusion, I started to feel the effect, […] so much was well again, my walking was much better, I had a lot more sensation, yes, my body was calm again, [DMT H] had brought a peacefulness to the MS, had encouraged the healing, so to speak. There was so much that returned, became better, so much that you’d believed would never come back.” [pwMS 8]; “Started [DMT K], MS knocked on the head. It wasn’t there anymore, not even a ripple. It was gone. There wasn’t even the tiniest bit of activity that I was aware of. […] I could do all kinds of things, unrestricted.” [pwMS 11]. Although pwMS commonly attributed improvements in symptoms to the DMT, it might also be that the improvements occurred due to relapse remission or psychological effects.
Coping with adverse effects and failure of DMTs
DMT application is associated with adverse effects which pwMS experience and cope with differently. Some took additional medication and therapies and have not perceived this as a burden, e.g. anti-allergic drugs or analgesics against influenza-like symptoms. But a few have suffered serious adverse effects, which also required a more stressful therapy.
Some patients have tolerated adverse effects to prevent disease activity as “the price to pay”: “My thyroid became overactive. You always think that won’t happen to me, those side effects won’t affect me. But unfortunately in my case, they did […]. Before I was diagnosed with the overactive thyroid, I just sat down on the floor and couldn’t get up. […] And it was clear when we started treating the thyroid it started getting better, a little better every week. […] But it’s all definitely better than being in hospital and sitting in a wheelchair […] I mean I was really ill before and now I feel great.” [pwMS 47]. Some pwMS also reported that they tolerate adverse effects which they did not perceive as very burdensome, such as hair loss, skin reactions at the injection site, flushes and gastrointestinal problems. Patients tolerate side effects if they feel stable and attribute this to the medication.
PwMS described unusual adverse effects of DMTs, which have not been reported by studies. Being aware that MS is the disease with 1000 faces, it is very challenging for patients to separate disease symptoms from other bodily sensations and side effects of DMTs. As people are always looking for causality, MS and DMT are first in line for such attributions.
Switching to another DMT
Decision-making process
Experiencing adverse effects or no benefit were the major factors for the decision to change DMT. Adverse effects or DMT failure were either detected during a clinical examination and possibly in combination with paraclinical measure such as laboratory values or MRI imaging; or pwMS noticed them by themselves due to a reflection on new or worsening symptoms: “That’s right, I took [DMT C] in the morning and just two hours later I had stomach pain, proper stomach cramps. I kept an eye on that for two or three days, because I thought it might just be a coincidence, could easily be something else. But it was always a couple of hours after taking a tablet that I started to feel ill, and then I…My neurologist was on holiday, sod’s law. I stopped taking them anyway without any consultation, for it seemed silly to take something that was causing me pain.” [pwMS 50]. The patients also reported that, although they had not experienced adverse effects during their therapy, they wanted or had to change their therapy because of anticipated adverse effects. Some interviewees did not want to accept constraints while still uncertain of the DMT’s benefits: “But if I take medication that restricts me, and when I don’t know if it’s even going to work in the end or not, well, the MS itself is enough, I don’t need to add medication into the mix. That was how the decision to change […] came about.” [pwMS 17]. Some patients took a break from DMTs after experiencing no benefit from them and decided later to begin a new DMT if they noticed further progression of the disease, for example. Some of the pwMS had a desire to discontinue a DMT or at least take a break (“drug holiday”), but this was mostly rejected or not considered by the physicians as even a short interruption of treatment was deemed unacceptable and therefore pwMS had to switch to another DMT.
Again, there were personal needs of pwMS which were important in the decision to switch DMTs. PwMS who have had experience with DMTs, their handling and adverse effects, want a DMT that does not make them constantly think about MS in their daily lives: “I was actually really happy when I got this. Not least because it meant an end to those weekly injections, the permanent confrontation with the illness. For this is quite different. You go in once a month and receive an infusion.” [pwMS 21]. The wish to have children also played a role in the women’s decision for DMT. Women who have taken a therapy not approved for pregnancy have to switch or interrupt it while trying to conceive. One woman explained that she preferred a DMT, which is administered in cycles as infusions, because it is approved for pregnancies after an appropriate period of waiting after the last cycle.
During the analysis, we noticed that the social environment was mentioned several times in relation to dealing with MS or handling injections. But it was hardly ever the case that pwMS said their significant others had any influence on the decision to switch a DMT. However, one pwMS reported that she changed her DMT not simply because of an adverse effect, but due to the responsibility for her children, too: “I bear responsibility for my children. If I hadn’t had children, I would have probably stuck with [DMT H]. [pwMS 47].
An involuntary withdrawal of the DMT was another factor for switching a DMT. PwMS described situations in which their previous medication was withdrawn, although they would have liked to continue it. A similar situation occurred for pwMS when they transitioned to SPMS and therefore switched to another DMT.
Some patients switched to a newly launched DMT by participating in studies, for example. The novelty of a therapy may not be the main argument, but it certainly aroused interest in this therapy and possibly was associated with the impression that a new therapy must be better than the old one. Conversely, one pwMS mentioned concerns about taking a recently approved new DMT: “And then [DMT J] entered the market. Yes. And I thought to myself, I could give that a shot. But also, with some reservations, what with it being new on the market, what’s it like. I felt a little bit like a guinea-pig.” [pwMS 45].
Coping with the decision to switch a DMT
Switching to another DMT evoked different emotional reactions. Some interviewees described this advocating a change in their DMT as a disappointment, especially when they did not perceive any adverse effects themselves, but laboratory abnormalities indicating organ dysfunction made this necessary: “I experienced absolutely no side effects. I felt really great on it. I was also sad that I was feeling positive and yet had to stop taking it, otherwise I’d have stayed on it for sure.” [pwMS 47]. One interviewee described the process of switching DMTs as a repeated psychological burden, because the switch meant that the DMT had not been successful, leaving fewer options and the uncertainty of whether the next DMT will be successful: “And so it was that feeling: okay, already one hasn’t worked and something new comes along and who knows if it will work? So that uncertainty and also disappointment, that was my feeling at the time.” [pwMS 36]. Several pwMS experienced relief at switching, because of the difficulty of administering the previous one or side effects.
44 PwMS have experienced at least two DMTs during their course of disease. There were eight people who have tried more than five DMTs. More than the half have experienced no treatment effect again, even after a change of DMT. Although therapy failed, pwMS kept on going and proceeded with other DMTs. One patient said that she was willing to try new DMTs over and over again and had confidence in physicians in this respect: “And that is actually great that we have a few treatments to try out and there will be the one you decide to stick with and there will be one that can help.” [pwMS 15].
Discontinuing a DMT
Decision-making process
Eight pwMS discontinued their treatment and did not start a new one. The patients recounted that no benefit of DMTs, adverse effects and burden in the mode of administration were among their reasons why: “It really was the case that the medication itself created more stress for me [doing the injections and the lipodystrophy as a side-effect] than the illness itself.” [pwMS 2]. Due to their negative experiences with DMTs, patients in this instance became critical of and felt a reluctance towards other DMTs.
One patient stated that she had stopped using a DMT because of the side effects, but also because she possibly had benign MS, having experienced one relapse in 10 years. Experience of the disease course over time may change patients’ attitudes towards treatment and may lead to discontinuation.
The transition from RRMS to SPMS was the criterion to stop the DMT for four pwMS. The reason was either a lack of accessibility to a DMT approved for the progressive MS course in the past or a limited number of DMTs remaining as an option.
Coping with the decision to discontinue treatment with a DMT
The decision against further treatment with DMT was associated with uncertainty because patients felt to bear a lot of responsibility within this decision: “Yes, at the beginning, it is definitely strange. Is it the right decision or isn’t it? But as I mentioned, I did dedicate a lot of thinking time to it and no longer having to inject is a real relief. […] In that respect I felt good.” [pwMS 2]. Ultimately, the patient felt comfortable with the decision.
Some pwMS perceived DMTs as a threat and describe how their well-being has improved after discontinuing: “I feel a sense of freedom.” [pwMS 4]. Other patients defended themselves when talking about their decision to stop treatment: “I tried it out with several medication therapies, gave it my best shot, didn’t resist them.”[pwMS 17];“I know from a friend of mine who is the same age as me, also has MS, a similar course […] I know, you can’t generalise, but although he did everything possible, tried out all possible medications, it got steadily worse right up to his death. Bearing that in mind, I really can’t say that I regret my decision about 15 years ago to stop taking any medication. It’s true, of course, that I can’t stand, that I can’t walk. But my head is still working well. And I am still alive.” [pwMS 29]. The latter pwMS justified his decision by comparing his disease state with that of his friend, and by doing so, critically appraised the benefit of DMTs.
For some pwMS, discontinuation meant accepting MS and impairments on a different level and enabling living more in the here and now: “And now I haven’t taken any further medication for three years. […] I want to keep on enjoying life, just as it is. Sure, there are limitations […]. But not everything has to do with MS. That’s my experience at least. You have to learn to listen in deeply to your body, get to know yourself.” [pwMS 4].
While having discontinued DMTs, the pwMS used other therapy approaches such as symptomatic treatment, corticosteroids, complementary and alternative medicines (CAMs): “And if I do then have to deal with more severe relapses or problems, then I’d prefer to rely on a course of cortisone.” [pwMS 17]; “So I do other things […] I smoke joints, […] I take sulphur, […] I drink lots of ginger tea, […] I go more for the natural remedies.” [pwMS 4].
MS without starting a DMT
Decision-making process
Nine pwMS decided not to take a DMT directly after diagnosis and continued thus for many years. In our sample, there were three pwMS (pwMS 39, 40, and 42) aged 50-59 years, who have never undertaken treatment with a DMT.
Some pwMS initially decided against a treatment with DMT because there was little or no choice of DMTs years ago.
The patients’ critical attitude towards conventional medicine and DMTs was another reason not to start with DMT. One pwMS, who has never used a DMT, recounted: “It is actually still not understood what actually causes MS, what the complicated interconnections are, and so on […] and then there are various drug therapies. […] But I found the very names scary, all the names these drugs have. Anyway, it was clear from the start there was no way I’d be taking any of them.” [pwMS 39]. The patient was additionally critical of DMTs because he did not consider the current state of MS research to be advanced. DMTs do not necessarily reduce relapses, and the long-term health benefit is not clear, which also causes feelings of uncertainty.
Another reason not to start a DMT is the absence of a recommendation by a physician for a DMT. One pwMS reported that because of this reason, she did not seek treatment with DMTs on her own: “So, when it comes to these drug therapies, no one ever told me I should take something […]. And I had a neurologist, […] he said himself that he adhered to things that are statistically proven. But if I were to take a different path, that would be fine, too. But it was more at that level; he didn’t contradict me. […] And with no one insisting upon it, I stopped […] seeking medication and I simply did nothing.” [pwMS 42]. Other pwMS, who live without DMT said that a physician had even recommended not to start with a DMT: “I should follow a healthy life-style. Shouldn’t smoke, and should do sport, and I shouldn’t eat too much pork. That was the long and the short of my doctor’s advice, rather than assigning me medication. [pwMS 18]; “Back then the doctor at hospital said, ‘Don’t give your body any substances, or it will get curious about them. So try to avoid them as long as you can’, and that was how I lived. […] I personally believed at the start that if I were to give my body something, then it would get used to it, and that might reduce the effectiveness of other mechanisms which are also important, and thus I told myself, no. As long as I am not restricted, then I won’t take anything.” [pwMS 40]. Here, the idea or approach of not accustoming the body to any substances seem to be present when reflecting on long-term medications.
A possibly benign course of MS and lack of perceived impairment caused by MS has led pwMS to decide against starting a DMT and not to do so for a long time: “Because it had been only a brief exceptional event, a relapse, that I had back then, and it cleared up pretty much within four to six weeks, and no residual damage. […] Yes, so I was ill for four weeks and then… Yes, it was simply suppressed then, the MS. And for the first three years I basically didn’t take any medication because there was nothing wrong with me. I was healthy, as far as I was concerned. And the neurologist I had then, he also said: ‘You can take this, or not, as you like.’ And at that time, when I was diagnosed, there were only two therapies. […] And it was like that: ‘You can take it or not, either way. We don’t know whether it helps.’ Yes, and when you’re 18, 19, or 20, you think ‘I’m not interested!’ And get on with living.” [pwMS 23].
Coping with the decision not to start treatment with a DMT
Patients described that they felt comfortable with their decision. One patient even felt lucky for not having been exposed to such a situation: “It was a stroke of luck for my life that no one forced me to take anything.” [pwMS 42].
PwMS took other treatment approaches such as relapse therapy, symptomatic treatment, as well as CAMs instead of a DMT. Using other therapy approaches makes pwMS feel (re)gaining control over the disease: “So, I tried out various things […] for example: […]meditation. You don’t simply sit there listening to music and struggling with the thoughts that come into your head, but rather we visualise in our mind what the life we want to live looks like. For our brain cannot differentiate between what is imagined and what is actually taking place and if we give that a positive turn, then we send into our body all the good things it needs to be healthy […] feeling good rather than feeling the fearfulness of a victim’s state.” [pwMS 2].
As mentioned before, pwMS who decided not to start a DMT seemed to be experiencing a benign course of MS with no noticeable impairment caused by MS. They moved forward with their life and were willing to tolerate impairment caused by the MS: “Sometimes minor relapses occurred, slight distortions in sensation, but nothing that was really of major significance, and it was only over the course of two or three years that the regularity increased a bit. […] I saw them on MRI images, where it was always: ‘oh, here are a couple of bright circles, those were relapses.’ And then I’d say, ‘I hadn’t noticed, but if you say so, there must have been.’” [pwMS 40].
Some people decided to wait for a time after diagnosis and not to take a DMT immediately. However, when people notice increased disease activity, they then start a DMT in the hope of reducing MS progression and relapses.