Impact of patient programs on adherence and persistence in inflammatory and immunologic diseases: a meta-analysis

Figures & data

Figure 1 Flow diagram of systematic literature search.

Abbreviation: I&I, inflammatory and immunologic.

Table 1 Characteristics of included studies

Study (country)	Study design	Disease area	Intervention	N	Comparison	N
Informational patient programs
Elkjaer et al (Denmark and Ireland)^Citation18	RCT	Ulcerative colitis	Web-based patient education	89	Conventional treatment and follow up in the IBD out-patient clinic	97
Homer et al (UK)^Citation7	RCT	Rheumatoid arthritis and psoriasis	Group counseling	30	Individual counseling	32
Lai et al (Malaysia)^Citation24	RCT	Osteoporosis	Pharmaceutical care and counseling	100	No counseling	98
Montori et al (USA)^Citation9	RCT	Osteoporosis	Decision aid	52	No decision aid	48
Moss et al (USA)^Citation19	RCT	Ulcerative colitis	Nurse delivered patient support program	15	Standard medication refill and follow up	36
Nielsen et al (Denmark)^Citation17	RCT	Osteoporosis	Group-based educational program	136	Standard prescribed therapy with visits at the general practitioner or clinic	130
Shu et al (USA)^Citation25	RCT	Osteoporosis	Educational intervention	593	No intervention	564
Solomon et al (USA)^Citation26	RCT	Osteoporosis	Telephone-based counseling	1,046	No counseling	1,041
Behavioral patient programs
Heilmann et al (USA)^Citation27	Retrospective study	Osteoporosis	Pharmacy based management service with follow up	291	Nurse based service without follow up	71
Ting et al (USA)^Citation28	RCT	Childhood-onset systemic lupus erythematosus	Cellular text messaging reminders	19	No reminders	22
Combined patient programs
Cook et al (USA)^Citation29	RCT	Ulcerative colitis	Telephone nurse counseling	278	No counseling	246
Moshkovska et al (UK)^Citation30	RCT	Ulcerative colitis	Tailored patient preference intervention	37	Standard care	34
Sewerynek et al (Poland)^Citation31	Prospective study	Osteoporosis	Patient counseling, biochemical information, and nurse assistance	29, 31, and 31	No counseling, biochemical information, or assistance	32
Stockl et al (USA)^Citation32	Retrospective study	Rheumatoid arthritis	DTM program	244	No DTM	244
Stockl et al (USA)^Citation8	Retrospective study	Multiple sclerosis	DTM program	156	No DTM	156
Tamone et al (Italy)^Citation33	RCT	Osteoporosis	Self-injection training and educational telephone follow-up program	382	No training, no follow up	398
Tan et al (USA)^Citation34	Retrospective study	Multiple sclerosis	Specialty care management program	3,125	No care management	868

Abbreviations: DTM, disease therapy management; IBD, Inflammatory bowel disease; RCT, randomized controlled trial.

Table 2 Adherence and persistence outcomes

Study (country)	Follow-up period (months)	Adherence	Persistence	Adherence outcomes (I vs C)	Persistence outcomes (I vs C)
Informational patient programs
Elkjaer et al (Denmark and Ireland)^Citation18	12	The compliance questionnaire included five questions with dichotomized answers: easy access to prescription, ability of relapse recognition, following the medical doctor’s advice, ability to self-initiate acute treatment, and adherence to 5-ASA treatment. In Denmark, patients’ answers regarding 5-ASA refill were compared with results from the e-prescription pharmacy database		Denmark: 73% vs 42% (P=0.005) Ireland: 73% vs 29% (P=0.03)	NR
Homer et al (UK)^Citation7	4	Adherence was defined as: “the extent to which the patient’s behavior matches agreed recommendation from the prescriber”	–	90% vs 69% (P=0.06)	NR
Lai et al (Malaysia)^Citation24	12	Adherence was defined as the average percentage of participants who were both persistent (continued bisphosphonate therapy) and compliant (took medication in the correct manner on the scheduled day). Pill count (by counting the number of tablets left at each visit) was used to measure adherence	Persistence (defined as the time in days from the date of the first dose of bisphosphonate until discontinuation of treatment) was obtained from supply records, using the pharmacy information system	97.70% vs 96.46% (P=0.322)	87.0% vs 89.8% (P=0.481)
Montori et al (USA)^Citation9	12	To assess medication adherence at 6 months, patients were telephoned and asked Haynes’ single-item adherence question (“Have you missed any of your pills in the last week?”). Pharmacy records were obtained to assess adherence and persistence	Persistence was estimated using proportion of patients who had ≥80% adherence	100% vs 98.20% (P=0.09)	170 (range: 30–180) days vs 180 (range: 28–180) days (P=0.38)
Moss et al (USA)^Citation19	6	Adherence was calculated based on refill data from pharmacies according to Steiner’s formula. Only patients with adherence >80% were considered to be adherent	–	67% vs 50% (P=0.3)	NR
Nielsen et al (Denmark)^Citation17	24	Adherence was defined as patients taking their medicine correctly at the appropriate time; patients who changed to another osteoporosis drug were considered to be adherent. Data on adherence were obtained via self-completed questionnaires	–	92% vs 80% (P=0.006)	NR
Shu et al (USA)^Citation25	3	Adherence was measured as MPRb. A patient who consistently filled prescriptions and had medication available for each day was 100% adherent	–	87.60% vs 88.80% (P=0.60)	Not used as it was not possible to determine the effect size, using the data given
Solomon et al (USA)^Citation26	12	Adherence was measured as MPRb. Pharmacy claims data from the collaborating state run pharmacy benefits program was used to calculate the MPR	–	49% vs 41% (P=0.07)	NR
Behavioral patient programs
Heilmann et al (USA)^Citation27	6	Adherence was defined as a MPRb of at least 80%	Medication persistence was defined based on the last medication purchase prior to the 365-day cutoff date. If the days’ supply, multiplied by 1.2 was equal to or greater than the number of days between the final prescription purchase and the cutoff date, then medication use was considered persistent. A factor of 1.2 was used to allow for an adherence rate of less than 100% but at least 80%	46% vs 28% (P=0.007)	54% vs 45% (P=0.19)
Ting et al (USA)^Citation28	12	Pharmacy refill adherence, defined as the percentage of the number of doses dispensed divided by the number of doses prescribed for the period of time between study visits and pharmacy refill dates, with pharmacy refill information serving as primary measure of medication adherence. Patients with adherence >80% were considered adherent	–	37% vs 27%	NR
Combined patient programs
Cook et al (USA)^Citation29	6	Adherence was defined as months of treatment completed. When participants reported adherence, RNs assessed what percent of the past month’s doses were taken as prescribed; Patients with adherence ≥80% were considered adherent	–	88% vs 57% (P<0.001)	NR
Moshkovska et al (UK)^Citation30	12	Nonadherence, based on analysis of urine samples, was defined as: • Complete nonadherence: undetectable (0 lg/mL) levels of 5-ASA or N-acetyl-5-ASA. • Partial nonadherence: 5-ASA <30 lg/mL and N-acetyl-5-ASA <90 lg/mL • Adherence: 5-ASA ≥30 lg/mL and N-acetyl-5-ASA ≥90 lg/mL In order to focus on identifying factors determining full adherence, partial and complete nonadherence were subsequently combined to form a single category for comparison with complete adherence	–	76% vs 32% (P=0.001)	NR
Sewerynek et al (Poland)^Citation31	12	The refill adherence was measured as MPRb. Patients with adherence >80% were considered adherent	Persistence was defined as the time in days from the date of prescription to the “run out” date in the treatment period. Patients were defined as “persistent” until a gap of >90 days was reached between the end of one prescribed drug series and the date of subsequent prescription; or until the patient switched to another bisphosphonate; or had a refill gap >30 days between the end of one prescription series and the beginning of the subsequent one	Educational group: 75.71% vs 54.03% Biochemical information group: 68.29% vs 54.03% Nurse assistance group: 71.18% vs 54.03%	Educational group: 269.72 (SEM 26.95) days vs 197.00 (SEM 26.91) days Biochemical information group: 249.19 (SEM 29.04) days vs 197.00 (SEM 26.91) days Nurse assistance group: 259.71 (SEM 25.10) days vs 197.00 (SEM 26.91) days
Stockl et al (USA)^Citation32	8	–	Discontinuation was defined as a gap of >30 days between the depletion date (fill date + number of days’ supply) for the last filled prescription and the end of the postidentification period	NR	89.30%a vs 59.40%a (P<0.001)
Stockl et al (USA)^Citation8	8	–	Medication persistence was defined as the number of days on therapy until a gap of >30 days Medication discontinuation defined as the gap of >30 days past the end of supply date for the last filled prescription and the end of the “Post” period	NR	219.80 (SD 80.30) days vs 176.50 (SD 92.00) days (P<0.001) 92.30%a vs 71.80%a (P<0.001)
Tamone et al (Italy)^Citation33	18	–	Persistence was defined as the number of patients continuing treatment until the end of the 18-month course	NR	85.60% vs 77.40% (P=0.006)
Tan et al (USA)^Citation34	12	–	Medication persistence was referred to the duration of time from initiation to discontinuation of therapy, while discontinuation was defined as failing to obtain any MS medication within 60 days after the depletion of the previous supply	NR	306.10 (SD 84.10) days vs 246.90 (SD 129.60) days (P<0.001)

Notes:

a Persistence rate was calculated from the discontinuation rate using the formula: persistence rate =100 - discontinuation rate.

b MPR was defined as the number of days for which medication was available divided by number of days in the follow-up period.

Abbreviations: ASA, aminosalicylic acid; C, control group; I, intervention group; MPR, medication possession ratio; MS, multiple sclerosis; NR, not reported; RN, registered nurse; SD, standard deviation; SEM, standard error of mean.

Figure 2 Program effectiveness on adherence, by type of patient program.

Notes: The study by Sewerynek et al³² is one study with three intervention groups: (1) the patient counseling group; (2) the biochemical information groups; and (3) the nurse-assistance group. The squares in the lines represent the effect estimate, the lines represent the length of the confidence interval, the diamonds represents the overall result of the meta-analysis.
Abbreviations: CI, confidence interval; IV, inverse variance.

Figure 3 Program effectiveness measured as % persistence.

Notes: The squares in the lines represent the effect estimate, the lines represent the length of the confidence interval, the diamonds represent the overall result of the meta-analysis.
Abbreviations: CI, confidence interval; IV, inverse variance.

Figure 4 Effect of intervention vs control on persistence (in days) in I&I.

Notes: The squares in the lines represent the effect estimate, the lines represent the length of the confidence interval, the diamonds represent the overall result of the meta-analysis.
Abbreviations: CI, confidence interval; I&I, inflammatory and immunologic; SD, standard deviation; IV, inverse variance.

Figure 5 Risk of bias summary.

Table S1 Search terms

Primary search terms	Secondary search terms
Allergies	Compliance
Ankylosing spondylitis	Medication adherence
Asthma	Adherence program
Behcet’s disease	Adherence intervention
Bursitis	Behavioral intervention
Celiac disease	Capacitance
Chronic pain	Compliance program
Crohn’s disease	Compliance intervention
Gout	Concordance
Idiopathic thrombocytopenic purpura	Medication possession ratio
Inflammatory bowel disease	Persistence
Multiple sclerosis	Persistence program
Osteoarthritis	Proportion of days covered
Osteoporosis
Psoriasis
Psoriatic arthritis
Rheumatoid arthritis
Sarcoidosis
Scleroderma
Sjögren’s syndrome
Systemic lupus
Systemic sclerosis
Tendonitis
Ulcerative colitis
Vasculitis

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