By law, smokers with severe tobacco dependence are entitled to receive one-off drug therapy for smoking cessation as part of evidence-based programmes reimbursed by the German statutory health insurance (SHI). Before deciding which drugs would be eligible, the Federal Joint Committee (G-BA) commissioned the Institute for Quality and Efficiency in Health Care (IQWiG) to assess the benefit of the four currently approved drugs for the treatment of severe tobacco dependence.
IQWiG has now published its final benefit assessment of bupropion, cytisine, nicotine and varenicline for smoking cessation, also in combination with each other, compared with no drug therapy. According to the findings, there is proof of greater benefit for treatment with nicotine and varenicline: study participants who took one of these drugs for smoking cessation in addition to supportive non-drug interventions were considerably more likely to be smoke-free six months after treatment than those without such additional drug therapy. The disadvantages of the drugs, such as side effects like sleep disturbance, headache, fatigue, nausea or skin irritation, did not question the clear advantages of the two drugs in the overall weighing of benefit and harm.
Analyses of subgroups of smokers in the studies of these two drugs show that the effect on permanent abstinence from smoking does not depend on the severity of tobacco dependence. In particular, the delimitation of the population with severe tobacco dependence according to the wording in the law and, consequently in the commission to IQWiG was intensively discussed during the commenting procedures on the report plan (protocol) and preliminary report.
There are no suitable published data on bupropion, cytisine or combination therapies for the subgroup analyses, and as no unpublished data were provided by the drug manufacturers, it is not possible to draw conclusions about their benefit.
Varenicline and nicotine: clear advantages despite side effects
Smokers who took varenicline were more likely to be smoke-free after six and twelve months than those without drug therapy. However, there were also disadvantages to taking varenicline, such as neuropsychiatric side effects (e.g. sleep disturbances, abnormal dreams, irritability), fatigue, nausea, dry mouth or headaches. However, the clear advantages of varenicline for smoking cessation are not questioned by these side effects. The severity of tobacco dependence had no discernible influence on the study results regarding the effect of varenicline. Overall, there is proof of a greater benefit of varenicline compared with no drug therapy for smoking cessation.
Nicotine is also an effective smoking cessation drug: smokers who took nicotine for tobacco dependence were more likely to be smoke-free after six months than those who did not. The study participants who took nicotine were also more likely to be smoke-free after twelve months, although the study data for this point in time is not as conclusive as for six months. Nicotine use was also associated with side effects such as headache, nausea, irritation of the mouth and throat, and itching. However, neither the disadvantages of nicotine in the form of side effects nor the less conclusive results on permanent abstinence from smoking after 12 months question the advantages of nicotine. As with varenicline, the severity of tobacco dependence had no discernible influence on the study results regarding the effect of nicotine. Overall, IQWiG also sees proof of a greater benefit of nicotine compared with no drug therapy for smoking cessation.
No assessment without evidence
IQWiG repeatedly asked both the manufacturer of bupropion and the authors of study publications on cytisine for complete information, but to no avail. Therefore, it was not possible to carry out subgroup analyses on the severity of tobacco dependence to assess its influence on the study results for the two drugs. The advantages and disadvantages of these drugs for smokers with severe tobacco dependence are thus unclear.
All the studies including drug combination therapy for tobacco dependence used bupropion in combination with nicotine or varenicline; because of the missing data on bupropion, it is also not possible to draw conclusions about the benefit of such combinations.
Severity of tobacco dependence as a prerequisite for reimbursement
The German Act on the Further Development of Health Care (GVWG) stipulates that smokers with severe tobacco dependence are entitled to receive one-time drug therapy for smoking cessation as part of evidence-based programmes reimbursed by SHI. Accordingly, the G-BA's commission to IQWiG for the benefit assessment of drug therapy for smoking cessation in severe tobacco dependence is formulated according to the Fagerström Test for Nicotine Dependence (FTND) or analogous classifications.
However, this restriction was criticized as being too narrow in several comments and during the oral hearing at IQWiG. For example, some people submitting comments argued that in other addictions, such as alcohol dependence, no distinction is made between mild, moderate and severe addiction. Instead, the "either/or" principle is applied without differentiation. However, this approach is not covered by the requirements of the law and IQWiG's commission, and the scientific literature also distinguishes between severe and less severe forms of tobacco dependence. The G-BA, as the decision-making body of the joint self-government of the German health care system, ultimately discusses and decides which drugs for smokers with severe tobacco dependence can be reimbursed by the SHI system. To this end, the G-BA must also define criteria for when someone is considered to be severely addicted to tobacco.
About the reporting procedure
On 18 March 2022, the G-BA commissioned IQWiG to assess the benefits of bupropion, cytisine, nicotine and varenicline for smoking cessation in severe tobacco dependence. IQWiG published the preliminary results, the preliminary report, in September 2023 and invited comments. Following the commenting procedure, the report was revised and sent to the G-BA as a final report in December 2023. The written comments submitted on the preliminary report were published in separate documents at the same time as the final report in January 2024. The English translation was published in December 2024. The Institute involved an external expert in the project.