i have not read that the risk of antibodies increases if stop/start. some ibd websites say this, but it seems to be a hunch and not a clinical finding.
in one study 90% of people restarting had successful treatment (lower ibd score)
/www.ncbi.nlm.nih.gov/pmc/articles/PMC4140086/] said...
Starting, continuing & stopping therapy
In the majority of patients, the decision to initiate therapy is relatively simple and based on symptoms of disease, prior treatment history and the risk tolerance of the patient and provider. The decision to initiate therapy can be more complex in patients with comorbid conditions such as advanced age, liver disease, heart failure, neurologic disease and/or prior or current malignancy. As discussed above, the treatment pursued should be based on a careful assessment of the risks associated with inadequate IBD therapy when compared with the risks associated with medical or surgical therapy. For patients with a history of malignancy, we consider the severity of the patient’s IBD, the type of malignancy, the ability to monitor for recurrence of the malignancy and the length of time between treatment of the malignancy and start of immune suppressant or anti-TNF-α treatment. A prospective cohort study of IBD patients found no increase in the risk of new or recurrent cancer in patients exposed to immune suppressants [169,170]. The transplantation literature reports that the risk of cancer recurrence is dependent on the type of cancer treated and time between completion of cancer therapy and initiation of immune suppression [171]. Thus, we try to delay initiation of immune suppressant or biologic therapy if possible in a patient with recent malignancy. If possible, patients with active malignancies should not receive immune suppressant or anti-TNF-α therapy. We recommend oncology consultation prior to initiating immune suppressant and/or anti-TNF-α therapy in patients with a history of recent malignancy. We also try to use mono-therapy as opposed to combination therapy in patients with a history of prior malignancy. If patients develop a malignancy on treatment, we assess the association of the malignancy with treatment. In most situations, there is no association between the malignancy and treatment and we often continue treatment after consultation with oncology. The development of skin cancer while on immune suppressant and/or anti-TNF-α therapy warrants further discussion. It is our practice not to stop the thiopurine for a single NMSC. However, if recurrent NMSC develops thiopurine cessation should be considered strongly. We would recommend discontinuation of anti-TNF-α therapy in a patient who develops melanoma on therapy.
The decision to continue, decrease or stop therapy is individualized and based on the patient’s disease history, response to current therapy, the specific complication (if present) and provider/patient preference. Even in patients who develop serious adverse effects such as serious infections, therapy may be continued if the risk/benefit ratio is favorable. Factors to consider when deciding if therapy can be continued include causality (i.e., did the treatment definitively cause the adverse event?), whether the adverse event was life-threatening and whether the adverse event is a recurrence of a prior similar event. For example, an otherwise healthy patient with a history of CD refractory to immune suppressant therapy on treatment with an anti-TNF-α agent develops pneumonia requiring hospitalization and is treated successfully with antibiotics. Because it is not clear that anti-TNF-α exposure led to pneumonia, it would be reasonable to continue therapy even though a serious infection occurred. However, if a similar patient were to develop disseminated histoplasmosis, we would stop anti-TNF-α therapy because the patient developed a life-threatening infection likely associated with treatment. In cases where therapy is stopped, surgical options could be considered, if appropriate, and/or consideration could be given to re-instituting medical therapy with an alternative agent depending on the patient’s clinical course.
Determining when therapy can be safely withdrawn in the absence of adverse events is hotly debated and was recently addressed by a European multidisciplinary expert panel [172]. In addition to safety of long-term monotherapy or combination therapy, cost of prolonged therapy with biologic agents is an increasing concern. Studies have attempted to characterize relapse rates in patients treated with immune suppressants, finding that in patients treated with immune suppressants, depending on their clinical characteristics, 40–60% relapse 5 years after discontinuation of immune suppressant therapy. However, retreatment was successful in 80% of patients who relapsed [173]. The ability to stop thiopurine therapy in CD patients has also been examined via a multicenter, double-blind, non-inferiority withdrawal trial. Patients in clinical remission on AZA for at least 42 months were randomized to continued AZA therapy or to placebo. Relapse occurred in 21% of patients assigned to placebo and 8% of patients who continued AZA [174]. Similar studies have examined the effects of anti-TNF-α withdrawal in patients on combination therapy [175]. Louis et al. followed 115 patients with CD prospectively who had been in steroid-free remission for at least 6 months and received IFX for at least 1 year in combination with an immune suppressant. The 1-year relapse rate was approximately 44% after cessation of IFX. Risk factors associated with relapse included male sex, lack of prior surgical resection, leukocytosis, anemia and elevation in C-reactive protein or fecal calprotectin. In this study, re-treatment with IFX was successful in 90% of patients [175]. In addition, a multicenter, prospective, randomized superiority trial was conducted to determine if continuing immune suppressant therapy beyond 6 months in patients receiving combination therapy contributed to the efficacy of biologic therapy. Van Assche et al. found that there was no difference in changes to IFX dosing in the group that stopped immune suppressant therapy versus the group that continued immune suppressant therapy. The authors concluded that immune suppressant therapy in combination with IFX offers no clear benefit beyond 6 months [176]. We do not advocate for cessation of therapy at this time for patients in clinical remission. However, the above data can be used in patients who experience adverse events of drug therapy, serious infection, opportunistic infection or malignancy to help counsel patients on the risks of stopping therapy.
Five-year view
The treatment options for patients with UC and CD continue to expand. Several new medications, including vedolizumab, ustekinumab and tofacitinib, may be approved for the treatment of patients with IBD. With approval of these drugs, long-term safety registries will be mandated by regulatory agencies to determine uncommon to rare side effects not identified in clinical trials. In addition, clinicians will be challenged to position these new agents in existing treatment algorithms for IBD.
It is likely that in the coming years more patients will be treated with biologic therapy, including biologic therapy in combination with immune suppressants. We anticipate that interactive decision aids will continue to be developed to help providers counsel patients on the benefits and risk of therapy. In addition, as we transition to an era of personalized medicine, new diagnostic and prognostic tools will be developed to help better predict which patients will respond to therapy and which patients are at greater risk for adverse effects of therapy. Additional research is needed to determine which patients can safely tolerate withdrawal of drug therapy.
Post Edited (DBwithUC) : 3/21/2017 4:44:29 PM (GMT-6)