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.

Background: Clinical trials in IPF are not designed to estimate long-term survival. This analysis used a survival model to predict life expectancy for patients with IPF receiving pirfenidone or BSC. Methods: Life expectancy was estimated by the area under the curve of parametric survival distributions fit to Kaplan-Meier survival data from clinical studies and IPF registries. Kaplan-Meier survival data for pirfenidone were derived from clinical studies (CAPACITY, ASCEND, RECAP). Kaplan-Meier survival data for BSC were obtained from two independent registries of patients with IPF: the Inova Fairfax Hospital database (n=815) and the National Jewish Health Interstitial Lung Disease (NJH-ILD) database (n=321). The best-fitting distributions were chosen by statistical consideration, visual inspection of the fitted curve and by clinical interpretation. To account for differences between patients enrolled in the clinical trials and the registries, covariate adjustment using propensity scores was used. Results: Mean life expectancy (95% confidence intervals) was calculated as: 8.7 years (7.7, 10.2) with pirfenidone; 5.9 years (5.1, 6.9) with BSC (Inova); and 6.1 years (5.7, 6.5) with BSC (NJH-ILD). Therefore, pirfenidone improved life expectancy relative to BSC by 2.8 years and 2.6 years as measured by the Inova and NJH-ILD registries, respectively. Conclusions: The survival model suggests that pirfenidone significantly improves life expectancy compared with BSC by almost 3 years in patients with IPF. Although these findings are based on cross-trial comparisons, they provide support for pirfenidone as an effective treatment option for IPF.

Background: No head-to-head trials have compared biologic treatments for early active RA (ERA).We evaluated the effectiveness of tocilizumab (TCZ) compared with other traditional and biologic DMARDs (tDMARDs and bDMARDs) in adult patients with moderateto-severe ERA naive to MTX or bDMARDs.Methods: A literature review identified randomized controlled trials (RCTs) of tDMARDs and bDMARDs in patients with ERA (duration <3 years) reporting efficacy outcomes (proportions of patients achieving ACR scores of 20, 50, 70 and 90; DAS for 28 joints (DAS28)-defined remission (DAS28 <2.6).Bayesian network meta-analysis was performed.For ACR response, data were analysed using a fixedeffects (FE) ordered probit model.For DAS remission, data were analysed with an FE binomial logit model.The analysis included only results for treatments at licenced doses.Sensitivity analyses were performed for treatment class and inclusion criteria.Results: 16 RCTs of tDMARDs (MTX, SSZ, HCQ), bDMARDs [abatacept (ABT), adalimumab (ADA), etanercept (ETN), infliximab (IFX), golimumab (GOL), TCZ), and tofacitinib (Tofa) were included.All bDMARDs plus MTX, triple tDMARD therapies, and TCZ and Tofa in monotherapy significantly increased response across all ACR categories versus MTX.Probabilities of ACR response to bDMARDs plus 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 for ETN or ADA.Only a subset of studies reported DAS remission.Treatment with Tofa or any bDMARD (AEMTX), except ADA alone, improved the likelihood of DAS remission versus MTX.TCZ (AE MTX) generated the highest probability of remission among bDMARDs and was significantly more effective than all other bDMARDs (AEMTX) and Tofa.Results were robust to sensitivity analyses.Conclusion: Based on ACR response, the expected efficacy of bDMARDs plus 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 are likely to be more effective than ETN alone.TCZ AE MTX is expected to have the highest probability of generating DAS remission.Disclosure statement: L.S. has acted as a consultant for Roche.

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 $6,570 per additional low disease activity score achiever to $14,265 per additional ACR 70% improvement criteria responder. The lifetime incremental cost-effectiveness ratio was $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.

To assess the cost-utility of Tocilizumab (TCZ) in the treatment of methotrexate (MTX)-naïve adults with active rheumatoid arthritis (RA) in Slovakia. A decision tree model was developed to reflect the early management of MTX-naïve adult RA patients in Slovakia. Efficacy, DAS28 remission, for each treatment in the model was derived from a network meta-analysis (NMA) of randomised controlled trials (RCTs) [Sawyer et al. 2015]. Benefits were measured in Quality Adjusted Life years (QALYs) derived by mapping DAS28 scores onto EQ-5D utility weights. The analysis was conducted from the third-party payer perspective, and included direct medical costs (drugs, administration, monitoring). The time horizon is one year, in line with the maximum follow-up period from RCTs. Incremental costs and QALYs associated with TCZ±MTX were compared to anti-tumour necrosis factors (TNFs), including adalimumab (ADA), etanercept (ETN) and infliximab (IFX), within their licensed indications. Each treatment was also compared to MTX alone. Variables related to efficacy, cost and utility were tested in the sensitivity analysis. TCZ±MTX had a lower incremental cost-effectiveness ratio (ICER) than other TNFs ±MTX when compared to MTX alone in base case. When compared head-to-head with TNFs, TCZ was cost-effective, with ICERs range from €6,500 to €16,000 per QALY gained in monotherapy and from €10,000 to €24,000 per QALY gained in combination therapy. Furthermore, TCZ+MTX dominated IFX+MTX. The full incremental analysis showed that TCZ±MTX was the next most cost-effective strategy after MTX. Results of the sensitivity analysis showed the efficacy variables and the assumption on the utility mapping formula have an impact on the ICERs. The results suggest TCZ is a cost-effective alternative to the approved and reimbursed TNFs, used either as monotherapy or in combination with MTX in the treatment of MTX-naïve adult RA patients in Slovakia.

We evaluated the effectiveness of traditional disease-modifying antirheumatic drugs (tDMARDs) and novel DMARDs, alone and in combination, in methotrexate- and biologic-naive adults with moderate to severe early rheumatoid arthritis (ERA; <3-year duration). Literature review identified randomized controlled trials (RCTs) of tDMARDs and novel DMARDs reporting efficacy outcomes (American College of Rheumatology [ACR] 20/50/70/90 response and Disease Activity Score at 28 joints [DAS28] remission). Data were pooled using Bayesian network meta-analysis techniques. For ACR response, data were analyzed using a fixed-effects ordered probit model, which makes efficient use of ordered categorical data and guarantees coherent prediction of multinomial response probabilities. For DAS28 remission, data were analyzed with a fixed-effects binomial logit model. Sensitivity analyses tested the effects of grouping treatments by class and broadening/narrowing inclusion criteria. Results from a synthesis of 16 RCTs of tDMARDs (methotrexate, sulfasalazine, hydroxychloroquine) and novel DMARDs (biologics [abatacept, adalimumab, etanercept, infliximab, golimumab, tocilizumab] and tofacitinib) indicated that biologics+methotrexate, triple tDMARDs, and tocilizumab and tofacitinib monotherapy significantly increased response across all ACR categories versus methotrexate. ACR response probabilities for biologics+methotrexate were not significantly different between agents. ACR response probabilities to novel DMARD monotherapy varied, trending toward higher values for tofacitinib and tocilizumab than etanercept or adalimumab. In studies reporting DAS28 remission, treatment with tofacitinib or biologics±methotrexate, except adalimumab alone, improved remission likelihood versus methotrexate. Tocilizumab±methotrexate generated the highest probability of remission among biologics and was significantly more effective than other biologics±methotrexate and tofacitinib. Results across outcomes were robust to alternative grouping of interventions and change in inclusion criteria. Based on ACR response, the expected efficacy of biologics+methotrexate, tofacitinib and tocilizumab monotherapy, and triple tDMARD therapy appeared higher than MTX in ERA. Tocilizumab±methotrexate was expected to have the highest probability of generating DAS28 remission and was significantly more effective than other biologics±methotrexate and tofacitinib.

BACKGROUND:Since 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. OBJECTIVE:The 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. METHODS:An 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. RESULTS:In 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. CONCLUSION:For 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.

To compare biologics as monotherapy or in combination with methotrexate (MTX) in terms of patient reported outcomes (PROs) in RA patients with an inadequate response to conventional DMARDs (DMARD-IR).

Background The pathogenetic pathways and clinical presentation of systemic juvenile idiopathic arthritis (sJIA) differs from other forms of juvenile idiopathic arthritis (JIA). As a result the common JIA treatments are less effective and cost-effective for patients with sJIA. Objectives To assess the cost-effectiveness of tocilizumab (TCZ) in Finnish sJIA patients with inadequate response to previous therapy with NSAIDs and systemic corticosteroids. Methods The cost-effectiveness of TCZ was analysed in a cohort of two year old patients using a spreadsheet based probabilistic Markov state transition model with three month model cycles and 16 year duration. In the first scenario (that matches treatment of sJIA with prominent joint symptoms) TCZ was compared to methotrexate (MTX) in a treatment sequence where both treatment comparators were followed by etanercept, adalimumab and abatacept. In the second scenario (that matches treatment of sJIA with prominent systemic symptoms) MTX was replaced with anakinra as a treatment comparator. In the model the patients switch on to the next treatment line when they do not get adequate treatment response (ACR response less than 30%). TENDER trial based efficacy estimates were used for TCZ whereas the efficacy of other treatments was based on adjusted indirect comparison of clinical trials selected based on systematic literature review [1]. The sJIA associated and response related resource use was based on Finnish expert opinion and valued with year 2010 Finnish unit costs. The analyses were performed from health care payer perspective. Results were presented as cost per quality adjusted life-year (QALY) gained using annual 3% discount rate. Results Treatment sequences initiated with TCZ, MTX and anakinra produced 4.47, 3.41 and 2.83 QALYs, respectively. An additional QALY gained on TCZ cost 15 181 euros when compared with MTX and 14 496 euros when compared with anakinra. Based on cost-effectiveness acceptability frontiers, TCZ had 93% and 88% probability for being cost-effective at the willingness to pay (WTP) level of 20 000 euros/QALY gained when compared with MTX and anakinra, respectively. At the WTP threshold of 27 000 euros/QALY gained in the TCZ vs. MTX comparison and 37 000 euros/QALY gained in the TCZ vs. anakinra comparison, the probability of TCZ being cost-effective reached 100%. The performed sensitivity analyses suggest that the results are most sensitive to changes in the assumed health care resource use. Due to conservative modelling assumptions (e.g. 16 year timeframe, stable TCZ efficacy in responders over time and low drug costs after loss of treatment response) the obtained results underestimate TCZ’s true cost-effectiveness. Conclusions TCZ is an effective and potentially cost-effective sJIA treatment in Finland. References Diamantopoulos A, LeReun C, Westhovens R, Dejonckheere F. Indirect comparison of ACR response of biologic treatments in active sJIA. Submitted to EULAR 2012 (EULAR12-2334). Disclosure of Interest T. Hallinen Shareholder of: ESiOR Oy, Consultant for: Several pharmaceutical (including Roche Oy), food industry, diagnostics and device companies, hospitals and academic institutions, Employee of: ESiOR Oy, E. Soini Shareholder of: ESiOR Oy, Consultant for: Several pharmaceutical (including Roche Oy), food industry, diagnostics and device companies, hospitals and academic institutions, Employee of: ESiOR Oy, A. Diamantopoulos Consultant for: F. Hoffman-La Roche Ltd., F. Dejonckheere Employee of: F. Hoffman-La Roche Ltd., V. Vihervaara Employee of: Roche Oy, A. Hautala Employee of: Roche Oy, K. Aalto Consultant for: Pfizer, Roche Oy, Speakers Bureau: Abbot, Roche, Sobi, and Pfizer

JIA ACR30 (62%), JIA ACR50 (59%), JIA ACR70 (54%) and JIA ACR90 (35%) response than ADA monotherapy (53%, 49%, 44% and 26%, respectively). On MTX background therapy and a JIA ACR30 placebo response of 53%, ADA had a higher expected probability of response at JIA ACR30 (76%), JIA ACR50 (75%), JIA ACR70 (66%) and JIA ACR90 (49%) than TCZ (72%, 70%, 61% and 44%, respectively). In neither monotherapy nor combination therapy did differences between TCZ and ADA reach statistical significance. Differences in the study populations, including previous use of biologics, were explored with sensitivity analysis. Conclusion Based on JIA ACR response rates from this analysis, the expected efficacy of ADA vs TCZ appears comparable in pcJIA. These data should be interpreted in the context of differences in the duration of the withdrawal phase, which was shorter in the TCZ study (CHERISH) than in the ADA trial and might have resulted in a smaller difference in the number of flares observed between placebo and TCZ. Differences in previous exposure to biologics might also have affected the results.

Background To date there are no head-to-head trials comparing the efficacy of biologic treatments for polyarticular-course JIA (pcJIA). Objectives To use statistical methods to estimate the relative efficacy of biologic treatments, alone and in combination with methotrexate (MTX), in the management of pcJIA by means of indirect comparison of randomised controlled trials (RCTs). Methods Based on a literature review, we identified RCTs of abatacept,1adalimumab2(ADA), etanercept,3infliximab4and tocilizumab5 (TCZ; CHERISH) in pcJIA. Comparative effectiveness was estimated on the reported American College of Rheumatology response rates (JIA ACR30/50/70/90) measured at the end of the randomised, double-blind phase by means of a Bayesian indirect comparison using a fixed-effects ordered probit model. Probabilities of achieving different levels of JIA ACR response were calculated for biologic treatments and placebo using all observed comparisons. Results The 5 RCTs identified showed differences in reporting JIA ACR responses with regard to methods of non-responder imputation during the blinded, controlled phase, allowing only for the comparison of ADA and TCZ. In the base-case analysis (Figure), for a JIA ACR30 placebo response of 31%, TCZ monotherapy had a higher predicted probability of achieving JIA ACR30 (62%), JIA ACR50 (59%), JIA ACR70 (54%) and JIA ACR90 (35%) vs ADA monotherapy, with 53%, 49%, 44% and 26%, respectively. On MTX background therapy and a JIA ACR30 placebo response of 53%, ADA had a higher expected probability of response at JIA ACR30 (76%), JIA ACR50 (75%), JIA ACR70 (66%) and JIA ACR90 (49%) vs TCZ, with 72%, 70%, 61% and 44%, respectively. In neither monotherapy nor combination therapy did differences between TCZ and ADA reach statistical significance. Differences in the study populations, including previous use of biologics, were explored with sensitivity analysis. Image/graph Conclusions Based on JIA ACR response rates from this analysis, the expected efficacy of ADA vs TCZ appears comparable in pcJIA. These data should be interpreted in the context of differences in the duration of the withdrawal phase, which was shorter in the TCZ study (CHERISH) than in the ADA trial and might have resulted in a smaller difference in the number of flares observed between placebo and TCZ. Differences in previous exposure to biologics might also have affected the results. References Lancet2008;372:383; N Engl J Med 2008;359:810; N Engl J Med 2000;342:763; Arthritis Rheum 2007;56:3096; Unpublished data from CHERISH Disclosure of Interest L. Sawyer Consultant for: F. Hoffmann-La Roche, A. Diamantopoulos Consultant for: F. Hoffmann-La Roche, H. Brunner Shareholder of: PRCSG, Grant/research support from: National Institutes of Health, Lupus Foundation, Cincinnati Center for Clinical and Transplantation Research, Consultant for: Roche, Novartis, GSK, MedImmune, Pfizer, BMS, F. De Benedetti Grant/research support from: Abbott, Pfizer, BMS, Roche, Novimmune, Novartis, SOBI, N. Ruperto Grant/research support from: Abbott, AstraZeneca, BMS Centocor, Lilly, Francesco Angelini, GSK, Italfarmaco, Merck Serono, Novartis, Pfizer, Regeneron, Roche, Sanofi Aventis, Schwarz Biosciences, Xoma, Wyeth, Consultant for: (to institution) Abbott, AstraZeneca, BMS Centocor, Lilly, Francesco Angelini, GSK, Italfarmaco, Merck Serono, Novartis, Pfizer, Regeneron, Roche, Sanofi Aventis, Schwarz Biosciences, Xoma, Wyeth, Speakers bureau: Abbott, Boehringer, BMS, Novartis, Astellas, Italfarmaco, MedImmune, Pfizer, Roche, F. Dejonckheere Employee of: Roche, C. Keane Employee of: Roche

To evaluate the cost-effectiveness of tocilizumab (TCZ) in the treatment of polyarticular juvenile idiopathic arthritis (pJIA) in the United Kingdom (UK). An individual sampling model was developed to reflect the health care system and treatment pathway in the UK. Benefits were measured in terms of Quality Adjusted Life years (QALYs) and were derived from HUI3 data collected by the Dutch Arthritis and Biologicals in Children (ABC) Register [Prince et al., 2011]. Costs were calculated from a National Health Service and Personal Social Services perspective. The analysis calculated incremental costs and benefits associated with the addition of first line TCZ to the standard care pathway involving etanercept (ETN), adalimumab (ADA), and abatacept (ABA). The economic model used efficacy inputs derived from an indirect comparison of TCZ and ADA [Sawyer et al., 2013]. Due to fundamental differences in the clinical trial populations and trial design, it was not possible to compare the response rates of TCZ with ETN and ABA. Therefore in the absence comparative data, the economic analysis assumed response rates for ETN and ABA were similar to ADA. Longer-term treatment discontinuation was linked to level of response and assumed to be independent of treatment. Base case results estimated incremental costs of approximately £1,750 and incremental QALYs of 0.1011. The incremental cost-effectiveness ratio (ICER) was £17,000 per QALY gained. The results of this analysis suggest that TCZ represents an efficacious and cost-effective addition to the current standard of care for treating pJIA patients in the UK.

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

To evaluate the cost-effectiveness of monotherapy TCZ in DMARD-IR patients intolerant of or contraindicated to MTX in the United Kingdom (UK). An economic model was developed to reflect the health care system and treatment pathway in the UK. In the model, disease severity is represented by the health assessment questionnaire (HAQ) score; a surrogate health outcome which can be translated to utility scores and ultimately quality adjusted life years (QALYs). The model captures the progression of the HAQ score for each individual patient. Benefits were expressed as QALYs. Costs were calculated from a National Health Service and Personal Social Services perspective. The analysis calculated incremental costs and benefits associated with the addition of TCZ in first line to the standard care pathway involving certolizumab pegol, etanercept and adalimumab. Efficacy data for comparator biologic monotherapies were available from monotherapy trials of adalimumab (van de Putte et al 2004), certolizumab pegol (Fleischmann et al 2009), and etanercept (Moreland et al 1999). TCZ efficacy was informed by results from the ADACTA study (Gabay et al 2012), a new head-to-head superiority trial of TCZ and adalimumab monotherapy in RA. The economic model used inputs derived through a mixed treatment comparison that indirectly compared TCZ monotherapy with the standard of care biologic monotherapy treatments used in the UK (Roche data on file). Base case results estimated incremental costs of approximately £20,230 and incremental QALYs of 0.88. The incremental cost-effectiveness ratio (ICER) was £22,950 per QALY gained. A probabilistic sensitivity analysis produced a very similar ICER of £23,200 per QALY gained. The results of this analysis suggest that TCZ monotherapy represents an efficacious and cost-effective addition to the current standard of care in the UK, for treating RA patients who are intolerant of or contraindicated to MTX.

Background Tocilizumab (TCZ) is indicated for the treatment of adult rheumatoid arthritis (RA) that has responded inadequately to one or more disease-modifying antirheumatic drugs (“DMARD-IR patients”). Whilst typically given with methotrexate (MTX), TCZ may also be administered as monotherapy in patients who are intolerant of or contraindicated to MTX. The cost-effectiveness of this approach compared with current standard care in MTX-intolerant/contraindicated DMARD-IR patients has not previously been undertaken. Methods An economic model was developed to reflect the healthcare system and treatment pathway in Scotland. In the model, disease severity is represented by HAQ score; a surrogate health outcome which can be translated to utility scores and ultimately QALYs. The model captures the progression of HAQ score for each individual patient in an individual simulation process. ACR response rates are used as a measurement of response to treatment as these are readily available from TCZ trials as well as from RCTs of the other therapies included in this model. Benefits were expressed as quality adjusted life years (QALYs). Costs were calculated from a National Health Service Scotland and Personal Social Services perspective and included treatment costs as well as patient-condition-related costs. The analysis calculated incremental costs and benefits associated with the addition of TCZ in first line to the standard care pathway involving certolizumab pegol, etanercept and adalimumab. Treatment effects for TCZ monotherapy were based on efficacy data from the ACT-RAY trial (Dougados et al 2011). Data from comparator medicines were sourced from available monotherapy trials of adalimumab (van de Putte et al 2004), certolizumab pegol (Fleischmann et al 2009), and etanercept (Moreland et al 1999). Results Base case results estimated incremental costs of about £24,000 and incremental QALYs of 0.88. The incremental cost-effectiveness ratio (ICER) was £27,000 per QALY gained. The model was most sensitive to patient weight (which drives drug cost) and the parameters used in the HAQ-to-utility estimation equation. A probabilistic sensitivity analysis produced a very similar ICER of £27,500 per QALY gained. Conclusions The results of this analysis suggest that TCZ monotherapy represents an efficacious and cost-effective addition to the current standard of care in Scotland, for treating RA patients who are MTX intolerant. Disclosure of Interest C. Gibbons Employee of: Roche Products Limited, A. Diamantopoulos Consultant for: Roche Products Limited, H. Pang Employee of: Roche Products Limited, C. Huertas Employee of: Roche Products Limited, F. Dejonckheere Employee of: F.Hoffmann-La Roche