Stepping Down Treatment in Chronic Spontaneous Urticaria: What We Know and What We Don’t Know

There are currently no reports of large and systematic studies on the duration of CSU treatment and reasons for stopping it. Such studies are currently under way, for example the UCARE DRUSOCU study, which assesses omalizumab drug survival in CSU. In our experience, reasons for stopping CSU treatment include safety concerns or issues, treatment burden, economic factors, patient requests to participate in a clinical trial, pregnancy or wanting to become pregnant, the onset of another disease or intake of a new treatment, and the hope that spontaneous remission has occurred.

4.1 The Role of Patient Concerns, Drug Safety, and Treatment Burden in CSU Treatment Discontinuation

Many CSU patients are worried about short- and long-term side effects when it comes to their medication, especially since they need to use it continuously over a long period of time, often many years. These concerns should be addressed by CSU-treating physicians. It is important to communicate to patients that antihistamines and omalizumab have been used for a long time, by many patients, and are generally considered to be safe, although side effects are possible. Long-term real-life studies on standard-dosed and higher than standard-dosed antihistamines and omalizumab should be performed to confirm and increase the confidence in the safety of these treatments and to address patients’ concerns with real-world evidence. The fact that CSU treatment, albeit of long duration, is not for life, should be communicated to patients, as it can increase their willingness to use and stay on prophylactic treatment. The burden of treatment of CSU with antihistamines or omalizumab is low, but not zero. Currently, it is unclear how often CSU treatment is stopped because of its burden or because of safety concerns or issues. From our experience, treatment burden and safety concerns or issues are rare causes of treatment discontinuation, although they can be important in some patients. When patients stop their treatment because of safety concerns or issues or because of the burden of treatment, they usually do this all at once, rather than by gradually decreasing the dose.

4.2 The Role of Economic Factors in the Discontinuation of CSU Treatment

The costs of CSU treatment are another important aspect to be considered. Treatment with omalizumab is expensive, even though it was demonstrated to be cost effective [23, 24]. Not every healthcare system has the capacity to carry those costs, especially for a longer period of time. The medical benefit must be in reasonable proportion to the costs. Patients on omalizumab treatment should, therefore, not receive further treatment after spontaneous remission has occurred. Since this can only be determined by stopping the treatment, protocols for discontinuation must balance the burden of relapse with the costs of treatment. In many countries, the decision on when and how to discontinue treatment in complete responders is that of the treating physician, as it should be. In some countries, however, the duration of omalizumab treatment is restricted by regulatory authorities, insurance companies, or the financial burden for patients who pay for treatment out of pocket.

4.3 The Role of Clinical Trials in the Discontinuation of Treatment

Over the past years, with several new treatments for CSU in development, we have seen increasing opportunities and patient interest in participating in clinical trials. The reasons for this are manifold and include incomplete response to current treatments, hope for receiving disease-modifying treatment, and the wish to help with the development of new and better treatments. Current treatment with omalizumab is an exclusion criterion for all ongoing and new clinical trials. This leads to patients requesting to stop their omalizumab treatment. When this happens, treatment is usually stopped immediately rather than tapered, in order to shorten the time to study participation.

4.4 The Role of Pregnancy and Wanting to Become Pregnant in the Discontinuation of Treatment

Most patients with CSU are female, and since the disease often occurs during the reproductive age, pregnancy is an important aspect to consider in the management of CSU [25]. Pregnancy is a common reason for the discontinuation of CSU treatment. The recent UCARE PREG-CU study [26] showed that more than 80% of CSU patients, when they decide to become pregnant, continue to use their medication. In contrast, two thirds of CSU patients who used regular treatment before pregnancy changed to another treatment or stopped their treatment altogether once the pregnancy began [26]. In our experience, fear of harming the unborn child is the main reason for this, although sgAHs and omalizumab are generally regarded as safe to use during pregnancy [27, 28]. Some women with CSU hope that their pregnancy will improve their urticaria, so that they no longer need treatment. In fact, the UCARE PREG-CU study demonstrated that chronic urticaria, during pregnancy, improves in about half of the patients [29]. Independent of the reason, when patients stop their treatment because they plan to become pregnant or because they are pregnant, they usually discontinue their medication all at once, rather than by tapering.

4.5 The Role of the Onset of Another Disease or Intake of a New Medication in the Discontinuation of Treatment

The onset of another disease, for example cancer, or the need for treatment of another disease, are rarely the reason for the discontinuation of CSU treatment, although they often cause concerns. Patients and physicians may think that the onset of another disease is caused by the CSU treatment received or that its continued use may negatively affect the newly diagnosed disease. Both are uncommon. None of our CSU patients treated with sgAHs or omalizumab, as of yet, discontinued their treatment because a new disease was diagnosed. Also, there are no reports that suggest that omalizumab is less safe or effective in CSU patients with comorbid malignancy. For now, the only contraindication to omalizumab is a history of hypersensitivity reactions to omalizumab [30], and in our experience and opinion, patients with comorbid malignancy can and should be considered for omalizumab treatment if needed.

The situation is similar when a new treatment needs to be started, especially a biologic treatment. Patients and physicians are often concerned that the current CSU treatment may interfere with the efficacy or safety of the new treatment needed, although this is usually unwarranted. None of our patients, as of now, discontinued their sgAH or omalizumab treatment, because another treatment had to be initiated. This includes other biologics [31,32,33,34].

4.6 The Role of Spontaneous Remission in the Discontinuation of Treatment

The most common reason for stepping down treatment in CSU patients is to check for spontaneous remission after achieving complete control and freedom of signs and symptoms. There are currently no biomarkers for the occurrence of spontaneous remission in treated patients without signs and symptoms [35].

In some studies, but not others, higher rates of relapse were linked to long pre-treatment disease duration, being female, fast response to treatment, or high baseline disease activity [36,37,38]. While these markers may predict relapse on a group level, they are not useful for the prediction of relapse or for guiding stepping-down decisions for individual patients. Thus, whether or not patients still need their treatment can only be determined by stopping it [7]. Relapse after discontinuation of treatment is the rule rather than the exception. In a recent study, two thirds of patients who discontinued omalizumab experienced relapse [39]. In our personal experience, this rate is even higher.

留言 (0)

沒有登入
gif