Psychosocial determinants of adherence with oral anticancer treatment: 'we don't need no education'.

INTRODUCTION: Given the potentially fatal consequences of inadequate adherence with oral anticancer treatment in persons with cancer, understanding the determinants of adherence is vital. This paper aims at identifying psychosocial determinants of adherence to oral anticancer treatment. METHODS: We reviewed the literature on psychosocial determinants of adherence with oral anticancer treatment, based on published literature in English, from 2015 to present. Literature searches were performed in PubMed, Embase, Web of Science, Cochrane library, Emcare, and PsychINFO, with 'cancer', 'medication adherence', 'psychology', and 'oral anticancer treatment' as search terms. The obtained 608 papers were screened by two independent reviewers. RESULTS: In the 25 studies identified, illness perceptions, medication beliefs, health beliefs, and depression were found to be the major psychosocial determinants of adherence to oral anticancer treatment; sociodemographic and clinical characteristics were found to be of no major importance. The quality of the identified studies as assessed by two independent reviewers was found to be acceptable overall. The majority of papers were from North America and focused on patients with breast cancer; sample size varied from 13 to 1371; adherence was assessed with questionnaires derived from various theoretical models, pill counts and electronic pharmacy records; illness perceptions reflecting adaptive coping, and medication beliefs reflecting high necessity and low concerns were found to be associated with adherence. CONCLUSION: Psychosocial concepts are major determinants of adherence with oral anticancer treatment. 'Beliefs about medicines' and 'illness perceptions' in particular determine adherence with this treatment. Studies aiming at impacting adherence would benefit from interventions with a solid basis in behavioral theory in order to help health care providers explore and address illness perceptions and medication beliefs. Pre-consultation screening of adherence behavior may be a helpful supportive approach to improve adherence. Blaming the victim ('patients should be educated about the importance of adherence') is better replaced by encouraging health professionals to identify and address maladaptive psychosocial determinants of adherence.

Association Between Bone Mineral Density and Autoantibodies in Patients With Rheumatoid Arthritis.

OBJECTIVE: Autoantibodies, such as anti-citrullinated protein antibodies (ACPAs), have been described as inducing bone loss in rheumatoid arthritis (RA), which can also be reflected by bone mineral density (BMD). We therefore examined the association between osteoporosis and autoantibodies in two independent RA cohorts. METHODS: Dual x-ray absorptiometry (DXA) of the lumbar spine and left hip was performed in 408 Dutch patients with early RA during 5 years of follow-up and in 198 Swedish patients with early RA during 10 years of follow-up. The longitudinal effect of ACPAs and other autoantibodies on several BMD measures was assessed using generalized estimating equations. RESULTS: In the Dutch cohort, significantly lower BMD at baseline was observed in ACPA-positive patients compared to ACPA-negative patients, with an estimated marginal mean BMD in the left hip of 0.92 g/cm2 (95% confidence interval [95% CI] 0.91-0.93) versus 0.95 g/cm2 (95% CI 0.93-0.97) (P = 0.01). In line with this, significantly lower Z scores at baseline were noted in the ACPA-positive group compared to the ACPA-negative group (estimated marginal mean Z score in the left hip of 0.18 [95% CI 0.08-0.29] versus 0.48 [95% CI 0.33-0.63]) (P < 0.01). However, despite clear differences at baseline, ACPA positivity was not associated with greater decrease in absolute BMD or Z scores over time. Furthermore, there was no association between BMD and higher levels of ACPAs or other autoantibodies (rheumatoid factor and anti-carbamylated protein antibodies). In the Swedish cohort, ACPA-positive patients tended to have a higher prevalence of osteopenia at baseline (P = 0.04), but again, ACPA positivity was not associated with an increased prevalence of osteopenia or osteoporosis over time. CONCLUSION: The presence of ACPAs is associated with significantly lower BMD at baseline, but not with greater BMD loss over time in treated RA patients. These results suggest that ACPAs alone do not appear to contribute to bone loss after disease onset when disease activity is well-managed.

Clinical and radiological outcomes of 5-year drug-free remission-steered treatment in patients with early arthritis: IMPROVED study.

OBJECTIVES: To determine the 5-year outcomes of early remission induction therapy followed by targeted treatment aimed at drug-free remission (DFR) in patients with early arthritis. METHODS: In 12 hospitals, 610 patients with early (<2 years) rheumatoid arthritis (RA) or undifferentiated arthritis (UA) started on methotrexate (MTX) 25 mg/week and prednisone (60 mg/day tapered to 7.5 mg/day). Patients not in early remission (Disease Activity Score <1.6 after 4 months) were randomised (single blind) to arm 1, adding hydroxychloroquine 400 mg/day and sulfasalazine 2000 mg/day, or arm 2, switching to MTX plus adalimumab 40 mg/2 weeks. Treatment adjustments over time aimed at DFR. Outcomes were remission percentages, functional ability, toxicity and radiological damage progression after 5 years. RESULTS: After 4 months, 387 patients were in early remission, 83 were randomised to arm 1 and 78 to arm 2. After 5 years, 295/610 (48%) patients were in remission, 26% in sustained DFR (SDFR) (≥1 year) (220/387 (57%) remission and 135/387 (35%) SDFR in the early remission group, 50% remission, 11% SDFR in the randomisation arms without differences between the arms). More patients with UA (37% vs 23% RA, p=0.001) and more anticitrullinated protein antibody (ACPA)-negative patients (37% vs 18% ACPA-positive, p<0.001) achieved SDFR.Overall, mean Health Assessment Questionnaire was 0.6 (0.5), and median (IQR) damage progression was 0.5 (0-2.7) Sharp/van der Heijde points, with only five patients showing progression >25 points in 5 years. CONCLUSIONS: Five years of DFR-steered treatment in patients with early RA resulted in almost normal functional ability without clinically relevant joint damage across treatment groups. Patients who achieved early remission had the best clinical outcomes. There were no differences between the randomisation arms. SDFR is a realistic treatment goal.

Predictive factors of radiological progression after 2†years of remission-steered treatment in early arthritis patients: a post hoc analysis of the IMPROVED study.

OBJECTIVES: To identify predictive factors of radiological progression in early arthritis patients treated by remission-steered treatment. METHODS: In the IMPROVED study, 610 patients with early rheumatoid arthritis (RA) or undifferentiated arthritis (UA) were treated with methotrexate (MTX) and a tapered high dose of prednisone. Patients in early remission (disease activity score (DAS) <1.6 after 4 months) tapered prednisone to zero. Patients not in early remission were randomised to arm 1: MTX plus hydroxychloroquine, sulfasalazine and prednisone, or to arm 2: MTX plus adalimumab. Predictors of radiological progression (≥0.5 Sharp/van der Heijde score; SHS) after 2 years were assessed using logistic regression analysis. RESULTS: Median (IQR) SHS progression in 488 patients was 0 (0-0) point, without differences between RA or UA patients or between treatment arms. In only 50/488 patients, the SHS progression was ≥0.5: 33 (66%) were in the early DAS remission group, 9 (18%) in arm 1, 5 (10%) in arm 2, 3 (6%) in the outside of protocol group. Age (OR (95% CI): 1.03 (1.00 to 1.06)) and the combined presence of anticarbamylated protein antibodies (anti-CarP) and anticitrullinated protein antibodies (ACPA) (2.54 (1.16 to 5.58)) were independent predictors for SHS progression. Symptom duration <12 weeks showed a trend. CONCLUSIONS: After 2 years of remission steered treatment in early arthritis patients, there was limited SHS progression in only a small group of patients. Numerically, patients who had achieved early DAS remission had more SHS progression than other patients. Positivity for both anti-CarP and ACPA and age were independently associated with SHS progression. TRIAL REGISTRATION NUMBERS: ISRCTN Register number 11916566 and EudraCT number 2006 06186-16.

Two-year results of disease activity score (DAS)-remission-steered treatment strategies aiming at drug-free remission in early arthritis patients (the IMPROVED-study).

BACKGROUND: Early suppression of disease activity in (rheumatoid) arthritis (RA) patients may result in drug-free remission and prevent damage. We assessed 2-year clinical and radiological outcomes of two disease activity score (DAS)-remission-steered treatment strategies in early arthritis patients. METHODS: Patients (n = 610) with early RA or undifferentiated arthritis (UA) were treated with methotrexate (MTX) and tapered high dose of prednisone. Patients in early remission (44/53 joints DAS <1.6) after 4 months tapered and stopped medication. Patients who did not achieve early DAS-remission were randomized to either MTX plus hydroxychloroquine plus sulphasalazine plus low dose prednisone (arm 1) or to MTX + adalimumab (arm 2). At four-monthly intervals, medication was tapered and stopped if DAS was <1.6 but restarted, increased or switched if DAS was ≥1.6. Proportions of (drug-free) DAS-remission (DFR) after 2 years and Sharp-van der Heijde scores (SHS) were analyzed separately for the treatment strategies and patients with RA and UA. RESULTS: After 2 years, 301/610 (49 %) patients were in DAS-remission and 131/610 (21 %) in DFR. In the early remission group 241/387 patients (62 %) were in DAS-remission and 111/387 (29 %) DFR. In arm 1 22/83 (27 %) and in arm 2 24/78 (31 %) were in DAS-remission, and 6/83 (7 %) and 7/78 (9 %), respectively, were in DFR. RA and UA patients achieved DAS-remission in comparable percentages (RA: 234/479 (49 %), UA: 64/122 (52 %), p = 0.25). More UA patients achieved DFR (41/122 (34 %)) compared to RA patients (89/479 (19 %), p<0.001). Mean (SD) DAS over time was 1.74 (0.58) across all patients, and median (IQR) SHS progression was 0 (0-0). CONCLUSIONS: After 2 years remission-steered treatment in early RA and UA patients, DAS-remission and DFR percentages were relatively low. Patients who achieved early remission more often achieved (drug-free) remission after 2 years than patients who needed additional treatment steps in the randomization arms, and more UA than RA patients achieved DFR. Overall, disease activity and radiologic damage progression in all patients were well suppressed. TRIAL REGISTRATION: http://www.controlled-trials.com/ISRCTN11916566 Registered 07/11/2006 and EudraCT number 2006-06186-16 Registered 16/07/2007.

Determinants of reaching drug-free remission in patients with early rheumatoid or undifferentiated arthritis after one year of remission-steered treatment.

OBJECTIVE: The aim of this study was to assess whether baseline characteristics in patients with undifferentiated arthritis or early RA affect the possibility of achieving drug-free remission after 1 year (DFR1 year) of early remission induction therapy. METHODS: We included 375 patients participating in the IMPROVED study who achieved remission (DAS < 1.6) after 4 months (early remission) and were by protocol able to achieve DFR1 year. Having started with MTX plus prednisone, patients tapered prednisone to zero; after 8 months, those still in remission tapered MTX to zero, while those not in remission restarted prednisone. Characteristics of patients achieving and not achieving DFR1 year were compared. Logistic regression was performed to identify predictors of DFR1 year. RESULTS: After 1 year, 119 patients (32%) were in DFR. Presence of RF, fulfilling the 2010 criteria for RA, and a low tender joint count were associated with achieving DFR1 year, whereas presence of ACPA was not. None of the baseline characteristics was independently associated with DFR1 year. DFR1 year was sustained for 4 months in 65% of the patients. ACPA-positive patients less often had sustained DFR than ACPA-negative patients (58% vs 80%, P = 0.013). CONCLUSION: After 1 year of remission-steered treatment, 32% of the patients who had achieved early remission after 4 months were able to taper medication and achieved DFR. Neither the presence of ACPA nor any other baseline characteristics were independently associated with achieving DFR1 year, but in ACPA-positive patients DFR was less often sustained.

Five-year outcomes of probable rheumatoid arthritis treated with methotrexate or placebo during the first year (the PROMPT study).

OBJECTIVE: To assess long-term disease outcome of undifferentiated arthritis (UA) after initial treatment with methotrexate (MTX) or placebo. METHODS: 110 patients with UA were randomised to receive MTX (n=55) or placebo (n=55) for 1 year. After 5 years the outcomes for diagnosis (rheumatoid arthritis, 1987 criteria (RA (1987)), UA or UA in remission) and radiographic progression were compared between treatment arms and anti-citrullinated protein antibody (ACPA)-positive and -negative patients. Outcomes were recalculated for patients who, with hindsight, might have been classified at baseline as having RA according to the 2010 criteria (RA (2010)). RESULTS: 25 patients in the MTX group and 29 in the placebo group progressed to RA (1987) (p=0.45). MTX delayed progression from UA to RA (1987) but only in ACPA-positive patients. Drug-free remission was achieved in 35 patients, 20 of whom were initially treated with MTX, and 32 were ACPA-negative. ACPA-positive patients had more radiographic progression, regardless of treatment. Forty-three patients (39%) could be reclassified as having had RA (2010) at baseline, 6/24 (25%) of whom achieved remission after placebo treatment. CONCLUSIONS: After 5 years there is no lasting benefit of a 1 year initial course of MTX for patients with undifferentiated arthritis, compared with initial placebo. Progression to classifiable RA was not suppressed, drug-free remission not induced and the progression of radiological damage was similar in both groups. Reclassification at baseline with the 2010 criteria showed that 25% of patients with RA (2010) achieved spontaneous drug-free remission.

Health-related quality of life and functional ability in patients with early arthritis during remission steered treatment: results of the IMPROVED study.

INTRODUCTION: The aim of this study was to investigate patient reported outcomes (PROs) of functional ability and health related quality of life (HRQoL) in patients with early (rheumatoid) arthritis during one year of remission steered treatment. METHODS: In this study, 610 patients with early rheumatoid arthritis (RA) or undifferentiated arthritis (UA) were treated with methotrexate (MTX) and tapered high dose of prednisone. Patients in early remission (Disease Activity Score (DAS) <1.6 after 4 months) tapered prednisone to zero and when in persistent remission, also tapered MTX. Patients not in early remission were randomized to either MTX + hydroxychloroquine + sulphasalazine + prednisone (arm 1) or to MTX + adalimumab (arm 2). Every 4 months, patients filled out the Health Assessment Questionnaire (HAQ) and the McMaster Toronto Arthritis Patient Preference Questionnaire (MACTAR), the Short Form 36 (SF-36) and visual analogue scales (VAS). Change scores were compared between treatment groups. The association with achieving remission was analyzed using linear mixed models. RESULTS: During year 1, patients who achieved early remission had the most improvement in PROs with scores comparable to the general population. Patients in the randomization arms showed less improvement. Scores were comparable between the arms. There was a significant association between achieving remission and scores of HAQ, MACTAR and physical HRQoL. CONCLUSIONS: In early arthritis, PROs of functional ability and HRQoL after one year of remission steered treatment reach normal values in patients who achieved early remission. In patients not in early remission, who were randomized to two strategy arms, PROs improved less, with similar scores in both treatment arms. TRIAL REGISTRATIONS: ISRCTN11916566 and EudraCT2006-006186-16.

Remission induction therapy with methotrexate and prednisone in patients with early rheumatoid and undifferentiated arthritis (the IMPROVED study).

AIM: Classifying more patients as rheumatoid arthritis (RA) (2010 American College of Rheumatology/European League Against Rheumatism criteria for RA) may improve treatment outcomes but may cause overtreatment in daily practice. The authors determined the efficacy of initial methotrexate (MTX) plus prednisone treatment in patients with 1987 or 2010 classified RA and undifferentiated arthritis (UA). METHOD: 610 recent onset RA or UA patients started with MTX 25 mg/week and prednisone 60 mg/day tapered to 7.5 mg/day in 7 weeks. Percentage remissions after 4 months were compared between RA (1987 or 2010 criteria) and UA. Predictors for remission were identified. RESULTS: With the 2010 criteria, 19% more patients were classified as RA than with the 1987 criteria, but similar remission rates were achieved: 291/479 (61%) 2010 classified RA and 211/264 (58%) 1987 classified RA patients (p=0.52), and 79/122 (65%) UA patients (p=0.46). Anticitrullinated protein antibodies (ACPA) positive RA patients achieved more remission (66%) than ACPA negative RA patients (51%, p=0.001), but also had a lower mean baseline Disease Activity Score (DAS) (3.2 vs 3.6, p<0.001). Independent predictors for remission were male sex, low joint counts, DAS and Health Assessment Questionnaire, low body mass index and ACPA positivity. CONCLUSION: Initial treatment with MTX and a tapered high dose of prednisone results in similarly high remission percentages after 4 months (about 60%) in RA patients, regardless of fulfilling the 1987 or 2010 criteria, and in UA patients. Independent predictors indicate that initiating treatment while disease activity is relatively low results in more remission.