Systematic review of global evidenceOverview

Two thousand two hundred and sixty-one studies were searched out of four databases, and 15 studies were added from the manual research of a systematic review.19 After removing 466 duplications, 1713 irrelevant studies during abstract screening, and 63 other ineligible studies by inclusion/exclusion criteria, 34 papers were included and assessed for content analysis (initiation: N=420–23; preference: N=824–31; discontinuation: N=832–39; initiation/preference: N=1340–52; initiation/discontinuation: N=153). The study selection flow diagram is shown in online supplemental figure 1. In terms of characteristics of these studies, 9 studies are qualitative studies while 25 are quantitative, among which 16 studies used a conjoint analysis design (including discrete choice experiment). Except for two studies with a general population23 26 and seven studies with mixed patients (at least two disease types among RA, AS, axSpA, psoriasis and PsA),27 29 33 35 38 48 52 16 studies were carried out in patients with RA,5 20–22 28 30 34 36 37 41–43 47 49–51 eight in patients with psoriasis24 31 32 40 44–46 53 and one in patients with axSpA.39 Thirty-one (91%) studies were conducted in Western countries, while the others were conducted in Asia (one from China30 and two from Japan36 46). Detailed information is shown in online supplemental tables 2–4.

Factors to determine the initiation, preference and discontinuation of b/tsDMARDs

Table 1 displays the four themes and corresponding sub-themes of factors in all three decision processes determined in this study. The sub-themes are grouped under the headings—SA, CA, MC and FA.

Initiation of b/ts DMARDs

Factors regarding SA raised awareness/information/knowledge, beliefs/concerns, availability of patient support programmes and personal health planning when initiating b/ts DMARDs. Sources of information or means to increase knowledge of b/ts DMARDs includes previous experience of biologics,20 47 professional manpower in hospitals and pharmaceutical companies,54 post-market surveillance48 as well as the internet.23 53 Also, support for patients, such as setting up a public education campaign or linking patients to pharmaceutical companies for enquiries or other services, would bolster patients’ knowledge of the potential serious consequences of initiating innovative medicines.20 48 53 The influence of personal or religious beliefs or factors on innovative medicines,48 and the need to restrict alcohol or other lifestyles changes42 could further affect patients’ willingness to use b/ts DMARDs. MC, including safety, efficacy, years on market, and administration route and frequency, are of interest to patients when they consider b/ts DMARDs for the first time. The main factor driving the initiation of b/ts DMARD from CA were clinical staff with extensive experience, while the cost of drugs and insurance approval were important from a financial perspective.

Preference for b/ts DMARDs

Information/knowledge/awareness, beliefs/concerns about b/ts DMARD, patient support programmes and personal health planning from SA can determine the preference and choice for b/ts DMARDs over the traditional DMARDs. Real-world evidence of b/ts DMARDs is an especially important source of information to improve public awareness on innovative treatments.48 MC are widely discussed to elicit preference for treatment options with safety, efficacy and administration management mentioned in detail. The preference for b/ts DMARDs will be violated if the drug is new to the market or requires frequent regular physical check-ups,42 repeated hospital day-care28 and laboratory tests.45 CA that determines the preference for b/ts DMARD include physicians’ preference for treatment choice, rheumatologists’ opinions and the availability of medical assistance during the subcutaneous injection. Except for high drug prices, concerns about personal expenses and insurance coverage tended to a reluctance to use b/ts DMARDs.

Discontinuation of b/ts DMARDs

From SA, the distribution and stock of drugs in hospitals due to geographic location, public beliefs and negative concerns about treatment effects are examined as a determinant of discontinuation of biological use.35 38 A wide range of personal health plans also challenges the continuous use of b/tsDMARDs, such as pregnancy desires, the need for vaccination and surgical procedures, mental health issues, the desire for perceived diet or exercise,32 37 38 53 as well as the desire for disease remission.36 53 MC, such as side effects, drug contraindications, non-toxic or toxic reasons, immediate or lasting treatment effectiveness, are identified from studies on the discontinuation of b/ts DMARDs. Financial concerns that inhibit adherence to b/ts DMARDs refer to the high cost of drugs,37 53 and non-insurance coverage.32–34 However, CA are beneficial to long-term adherence of b/ts DMARDs by maintaining a good communicative relationship between patients and rheumatologists.38

Frequency of themes in decision-making process

Although the four themes were consistently reported in descending order of frequency throughout the decision-making processes, the frequency of each theme varied among the initiation, preference and discontinuation of b/ts DMARDs (figure 2, details in online supplemental tables 5–7). As for initiation, MC (83%) was the most frequently reported factor, followed by SA (56%), FA (39%) and CA (22%). Similarly, preference for b/ts DMARDs was also impacted by MC (86%), SA (43%), FA (33%) and CA (19%). Factors related to MC and SA were both reported in 78% of studies on the discontinuation of b/ts DMARDs, while FA and CA were cited at 56% and 11%, respectively. During the decision processes involving initiation, preference and discontinuation, MC, SA as well as FA were the three most frequently investigated factors whereas CA was given less consideration among the included studies.

Figure 2

The frequency of four themes in three decision making processes.

Survey of Hong Kong observation

We received 223 effective responses out of 255 distributed questionnaires. Detailed information on the baseline characteristics of participants is listed in online supplemental table 8. Consistent with the three different decision-making processes found in the systematic review, the survey results are presented with respect to barriers to access, preference for, and discontinuation of DMARDs treatments.

Barriers to accessing local financial support programme

Results from the systematic review showed that financial support is an essential factor to consider in the initiation of, preference for and discontinuation of medication. The survey discussed the difficulties that might be encountered during the application process. Thirty-four patients successfully received financial support out of 38 patients having applied. One hundred and eighty-five (82.6%) patients did not apply for the financial support programme. Apart from those who were not eligible or could not fulfil the clinical criteria for application, a considerable number of 41 patients (out of 223, 18.4%) were unaware that they could apply for the fund. Thirty-three (out of 223,14.8%) patients felt that the application procedures were too complicated.

Preference for taking DMARDs

MC are strongly associated with the selection of novel treatments since treatment efficacy and the probability of severe adverse events would be prioritised when patients consider DMARDs. In accordance with the fact that SA plays an important role in choosing b/ts DMARDs from the systematic review, the availability of government or charity subsidisation is also strongly solicited among survey respondents (table 2).

Table 2

Preference of attributes in considering drug use

Discontinuation of medication

Among 223 responses, 74 (33.2%) reported that they had stopped taking medicine in the last 3 months. Twenty-eight patients (out of 109, 25.7%) felt self-estimated improvement in disease conditions was the most common reason for discontinuation, followed by drug side-effects reported by 26 patients (out of 109, 23.9%) and cost-related concerns mentioned by 20 patients (out of 109, 18.3%). Physician-assessed improvement in disease conditions was another principal reason to consider, reported by 17 patients (out of 109, 15.6%). The inconvenience of drug use was least considered in quitting drugs, which accounted for three patients (out of 109, 2.8% of total responses) (figure 3). The findings were well aligned with the fact that SA such as the desire for disease remission, MC and FA are barriers to be considered and would certainly impact patients’ adherence to b/ts DMARDs according to the global evidence.

Figure 3

Main reasons for discontinuing medication in the last 3 months.