F. Dejonckheere

Tocilizumab in the Treatment of Rheumatoid Arthritis: A Cost-Effectiveness Analysis in the UK

BackgroundSince receiving a positive recommendation in England, Wales and Scotland, tocilizumab (TCZ) is one of the options available to clinicians for the treatment of rheumatoid arthritis (RA) patients in the UK.ObjectiveThe objective of this study was to evaluate the cost effectiveness of adding TCZ to the current treatment sequence of RA patients from a UK payer’s perspective over a patient lifetime horizon.MethodsAn individual sampling model was developed to synthesise all clinical and economic inputs. Two scenarios were explored separately: patients contraindicated to methotrexate (MTX) and those MTX tolerant. For each scenario, the analysis compared three strategies. The standard of care (SoC) strategy included a sequence of the most commonly prescribed biologics; the other two comparator strategies considered the addition of TCZ to SoC at first line and second line. Patient characteristics were representative of UK patients. Treatment efficacy and quality-of-life evidence were synthesised from clinical trials and secondary sources. An analysis of a patient registry informed the model parameters regarding treatment discontinuation. The safety profile of all treatments in a given strategy was based on a network meta-analysis and literature review. Resource utilisation, treatment acquisition, administration, monitoring and adverse event treatment costs were considered. All costs reflect 2012 prices. Uncertainty in model parameters was explored by one-way and probabilistic sensitivity analysis.ResultsIn the MTX-contraindicated population, if TCZ was added to the SoC in first line, the estimated incremental cost-effectiveness ratio (ICER) was £7,300 per quality-adjusted life-year (QALY) gained; if added in second line, the estimated ICER was £11,400 per QALY. In the MTX-tolerant population, the estimated costs and QALYs of the TCZ strategy were similar to those of the SoC strategy. Sensitivity analysis showed that parameters that affect the treatment cost (such as patient weight) can have a noticeable impact on the overall cost-effectiveness results. The majority of the other sensitivity analyses resulted in modest changes to the ICER.ConclusionFor the treatment of RA in MTX-tolerant and contraindicated patients, the addition of TCZ to the SoC was estimated to be a cost-effective strategy.

Economic evaluation of tocilizumab monotherapy compared to adalimumab monotherapy in the treatment of severe active rheumatoid arthritis

OBJECTIVES To estimate the cost-effectiveness of tocilizumab (TCZ) monotherapy (Mono) versus adalimumab (ADA) Mono from the US payer perspective in patients with rheumatoid arthritis for whom methotrexate is inappropriate. METHODS We compared TCZ Mono (8 mg/kg monthly) with ADA Mono (40 mg every other week), using efficacy results from a head-to-head study, ADalimumab ACTemrA (ADACTA). We calculated the incremental cost per responder (achievement of American College of Rheumatology [ACR] 20% improvement criteria, ACR 50% improvement criteria, ACR 70% improvement criteria, or low disease activity score) for TCZ versus ADA at 6 months. A patient-level simulation was used to estimate the lifetime incremental cost per quality-adjusted life-year (QALY) of initiating treatment with TCZ Mono versus ADA Mono. Both drugs are followed by an etanercept-certolizumab-palliative care sequence. Nonresponders discontinue at 6 months; responders experience a constant probability of discontinuation. Discontinuers move to the next treatment. ACR responses produce changes in the Health Assessment Questionnaire (HAQ) score. We mapped the HAQ score to utility to estimate QALYs. Costs include those related to hospitalization and those related to treatment (drug acquisition, administration, and monitoring). Probabilistic and one-way sensitivity analyses were conducted, along with several scenario analyses. RESULTS Compared with ADA, TCZ was more effective, with an estimated 6-month incremental cost ranging from

Validity of Cost and Utility Results

6,570 per additional low disease activity score achiever to

Survival in Idiopathic Pulmonary Fibrosis: Perspectives from Pulmonary Arterial Hypertension

14,265 per additional ACR 70% improvement criteria responder. The lifetime incremental cost-effectiveness ratio was

AB0432 Efficacy of Biologic Treatments in Early Active Rheumatoid Arthritis: an Indirect Comparison

36,944/QALY. CONCLUSIONS TCZ Mono is projected to be cost-effective compared with ADA Mono in patients with severe rheumatoid arthritis for whom methotrexate is not appropriate, from a US payer perspective.

THU0308 Indirect comparison of ACR response of biologic treatments in active SJIA

Sir, We read with interest the research conducted by Nguyen and colleagues to identify the costeffective agent for treatment of moderately to severely active rheumatoid arthritis (RA) from the US healthcare payer’s perspective. We are perplexed by the reported results for cost and utilities. The model time horizon is set to 5 years; however, the estimated utility exceeds 5 QALYs and is over 10 QALYs for some of the strategies (table V). Can the authors clarify how this calculation was made? Furthermore, the acquisition cost of methotrexate (MTX) per cycle is 5% of that for etanercept (table III). In addition the cost of a non-responder (which includes acquisition and administration costs of tocilizumab and extra physician visits) is still lower than that of the cost of etanercept. Can the authors clarify the difference in the total cost of MTX and etanercept strategies (Delta~

THU0305 Cost-utility of tocilizumab in the treatment of systemic juvenile idiopathic arthritis in finland

US5000 in table V), given thatMTX and ‘nonresponders’ cost less? We understand from the paper that serious infection costs are also included in the above estimates for the total strategy costs. However, the incidence of serious infections is reported to be similar for both comparators: MTX and etanercept (~3.5%) [table S3 in the Supplemental Digital Content], and therefore it is unclear how this could account for the difference in costs between the two strategies. Furthermore, is this similarity in the safety profile of the two agents plausible considering MTX is an oral therapy? We are grateful for the authors’ comments and clarification and are interested to know if any of our remarks affect the study conclusions.

Comparative Efficacy of Novel DMARDs as Monotherapy and in Combination with Methotrexate in Rheumatoid Arthritis Patients with Inadequate Response to Conventional DMARDs: A Network Meta-Analysis

DISCLOSURES Maher has received grants, consulting fees, and speaker fees from GlaxoSmithKline and UCB and grants from Novartis. He has also received consulting fees and speaker fees from AstraZeneca, Bayer, Biogen Idec, Boehringer Ingelheim, Cipla, Lanthio, InterMune International AG (a wholly owned Roche subsidiary since 2014), F. Hoffmann-La Roche, Sanofi-Aventis, and Takeda. Maher is supported by a National Institute for Health Research Clinician Scientist Fellowship (NIHR Ref: CS:-2013-13-017). Dejonckheere is an employee of F. Hoffmann-La Roche. Nathan has received consulting fees from Roche-Genentech and Boehringer Ingelheim. He is also on the speakers bureau for Roche-Genentech and Boehringer Ingelheim and has received research funding from both companies. All authors contributed equally to study concept and design, data collection and analysis, and manuscript preparation.

Comparative efficacy of biologics as monotherapy and in combination with methotrexate on patient reported outcomes (PROs) in rheumatoid arthritis patients with an inadequate response to conventional DMARDs – a systematic review and network meta-analysis

Background To date, no head-to-head trials have been conducted comparing the efficacy of biologic treatments for early active rheumatoid arthritis (ERA). Objectives To evaluate the effectiveness of tocilizumab (TCZ) compared with other traditional and biologic disease-modifying antirheumatic drugs (tDMARDs and bDMARDs), alone and in combination, in adult patients with moderate to severe ERA who have not been treated with methotrexate (MTX) or bDMARDs. Methods A literature review was undertaken to identify randomized controlled trials (RCTs) of tDMARDs and bDMARDs in patients with ERA (duration, <3 years) that reported efficacy outcomes, including the proportions of patients achieving American College of Rheumatology (ACR) scores of 20, 50, 70, and 90 and disease activity score (DAS28)–defined remission (DAS28<2.6). Study data were pooled using Bayesian network meta-analysis techniques. For ACR response, data were analyzed using a fixed-effects (FE) ordered probit model, which makes efficient use of ordered categorical data and guarantees coherent prediction of multinomial response probabilities. For DAS remission, data were analyzed with an FE binomial logit model. The analysis included only results for treatments in licensed doses. Sensitivity analyses tested the effects of grouping treatments by class and broadening and narrowing inclusion criteria. Results We included 16 RCTs of tDMARDs (MTX, sulfasalazine [SSZ], hydroxychloroquine [HCQ]), bDMARDs (abatacept [ABT], adalimumab [ADA], etanercept [ETN], infliximab [IFX], golimumab [GOL], and TCZ), and tofacitinib (Tofa). Results indicate that all bDMARDs+MTX, triple tDMARD therapies, and TCZ and Tofa in monotherapy significantly increased response across all ACR categories versus MTX (Figure). Probabilities of ACR response to bDMARDs+MTX were broadly similar, with no significant differences between agents. Probabilities of ACR response to bDMARDs in monotherapy were more varied, with a trend toward higher values for Tofa and TCZ than ETN or ADA. Only a subset of studies reported DAS remission. Results show that treatment with Tofa or any bDMARD (± MTX) except ADA alone improved the likelihood of DAS remission versus MTX. TCZ (± MTX) generated the highest probability of remission among bDMARD agents and was significantly more effective than all other bDMARDs (± MTX) and Tofa. Results across both outcomes were robust to alternative grouping of interventions and to change in the inclusion criteria. Figure 1. Median relative treatment effects vs MTX (95% credible interval). PRD, prednisone/prednisolone. Conclusions Based on ACR response, the expected efficacy of bDMARDs+MTX, Tofa and TCZ monotherapy, and triple tDMARD therapy appears comparable in early RA. TCZ and Tofa in monotherapy are more effective than ADA alone and likely to be more effective than ETN alone. TCZ ± MTX is expected to have the highest probability of generating DAS remission and is significantly better than other bDMARDs ± MTX and Tofa. Disclosure of Interest L. Sawyer Consultant for: Roche, S. Chang Consultant for: Roche, A. Diamantopoulos Consultant for: Roche, F. Dejonckheere Employee of: Roche DOI 10.1136/annrheumdis-2014-eular.2177

Predicting Life Expectancy for Pirfenidone in Idiopathic Pulmonary Fibrosis

Background To date, no biologic treatments other than tocilizumab (TCZ) have been approved in active Systemic Juvenile Idiopathic Arthritis (SJIA). Some however are used off label. Published evidence on their efficacy in SJIA is scarce, and there is no head-to-head data from randomised clinical trials (RCT) on the comparative efficacy of biologic treatments in SJIA. Objectives This analysis considers the current evidence on ACR responses of SJIA patients on biologics (used on and off label), synthesises this information, and explores efficacy differences. Methods A systematic literature review was conducted to identify RCTs that report ACR responses of SJIA patients on any biologic treatment, initially limited to SJIA, then extended to include any JIA subtype population. Reported ACR responses were compared with TCZ responses from the TENDER study,1 using an adjusted indirect comparison, comparing the relative risks of the clinical trials.2 The following outcomes were considered; ACR30 response with absence of fever, ACR30 response alone, ACR50, ACR70 and ACR90 response. Where needed, reported ACR responses were corrected to control for the differences in subtype disease. Results The initial literature review identified only one RCT with data on anakinra (ANK).3 The extension of the review yielded more results. However, only one additional study, with evidence on infliximab (INF), was deemed appropriate for comparison with TENDER, due to study design.4 The indirect comparison on ACR30 response without fever shows that patients on TCZ are more likely to achieve this outcome with TCZ than with ANK, although not statistically significant (RR=1.91; CI.: 0.84, 4.37). In ACR30 response alone the analysis shows statistical significance in favour of TCZ (RR=2.37 CI.: 1.10, 5.10). ACR50, 70 and 90 responses were not reported. In the comparison with INF, assuming no correction for the differences in the population subtype between the trials, patients treated with TCZ are also significantly more likely to reach ACR 30 response (RR=2.85 CI.: 1.38, 5.87), as well as ACR50 and ACR70 response. If a correction is applied the response with TCZ increases comparing to INF. ACR90 response was not reported. Conclusions There is a dearth of evidence in the literature to infer on efficacy differences across all biologics used for the treatment of SJIA patients. Based on the current evidence and the analysis conducted, patients on TCZ, the only approved biologic treatment for SJIA to date, are roughly 2-3 times more likely to achieve ACR response than if treated with ANK or INF. References De Benedetti F. Efficacy and Safety of Tocilizumab in Patients with SJIA: TENDER 52-Week Data. EULAR 2011 Bucher HC, Guyatt GH, Griffith LE et al. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 1997;50:683-91. Quartier P, Allantaz F, Cimaz R et al. A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial). Ann Rheum Dis 2011;70:747–754. Ruperto N, Lovell DJ, Cuttica R et al. A randomized, placebo-controlled trial of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis. Arthritis Rheum. 2007 Sep;56(9):3096-106. Disclosure of Interest A. Diamantopoulos Consultant for: Hoffman-La Roche, C. LeReun Consultant for: Hoffman-La Roche, R. Westhovens Consultant for: Hoffman-La Roche, F. Dejonckheere Employee of: Hoffman-LaRoche