Iguratimod at the EULAR 2020 Online Meeting

Since 2012 I've been looking at iguratimod [1]. Iguratimod is a conventional synthetic disease modifying anti-rheumatic drug (csDMARD); chemical formula: N-(3-Formamido-4-oxo-6-phenoxy-4H-chromen-7-yl)-methanesulfonamide. Iguratimod is characterized by inhibitory effects on immunoglobulin production in B cells as well as inhibiting cytokine production. Its' mode of action comes by suppression of nuclear factor kappa B (NF-kB) activation and RANKL production.

There have been four studies presented at the EULAR 2020 Online Meeting and one publication in Clinical Rheumatology.

K. Katayama and colleagues presented [2]: „SAT0146 INHIBITION OF RADIOGRAPHIC PROGRESSION BY IGURATINOD IN 116 JAPANESE RHEUMATOID ARTHIRITIS PATIENTS DESPITE CONVENTIONAL SYNTHETIC DISEASE-MODIFYING ANTIRHEUMATIC DRUGS THERAPY“. The study looked at 116 patients after one year of therapy; joint damage was evaluated by modified total Sharp scoring (mTSS) and RA activity was measured by DAS28-ESR. „Iguratimod suppressed not only clinical activities but also joint destruction in RA patients resistant to csDMARDs therapy.“

D. Kobayashi and colleagues presented the following study [3]: „SAT0147 EFFICACY AND SAFETY OF IGURATIMOD AS FIRSTLINE DISEASE-MODIFYING ANTIRHEUMATIC DRUG THERAPY FOR PATIENTS WITH RHEUMATOID ARTHRITIS“. The prospective single-center study aimed at efficacy and safety of iguratimod as a first-line DMARD in patients with rheumatoid arthritis. Conclusion: „Our study indicates IGU is safe and effective for DMARD naive RA patients. Starting treatment with IGU might be a new and effective strategy for RA

patients without previous use of a DMARD.“ Not much new information. The results are congruent with former studies.

T. Miyamoto and colleagues looked at RA patients with inadequate response to adalimumab [4]: „AB0350 EFFICACY OF ADDING IGURATIMOD THERAPY IN RHEUMATOID ARTHRITIS PATIENTS WHO HAD INADEQUATE RESPONSE TO BIOLOGIC DMARDS“. The authors looked at 107 RA patients receiving adalimumab plus methotrexate. The study is not blinded, no placebo arm. Results: „Mean DAS28-ESR, SDAI, CDAI were significantly decreased from the initiation of IGU treatment at 24 weeks (3.1→2.3, 7.1→2.7, 6.5→2.4), at 52 weeks (2.1, 2.4, 2.0). Remission rates of DAS28-ESR, SDAI, CDAI were 69.2%, 68.2%, 70.1% at 24 weeks, 74.8%, 78.5%, 79.4% at 52 weeks.“ I hab´ve problems with the statistics of this study. However the conclusion seems to be correct: „IGU might be a new RA treatment option for aiming remission in patients who had inadequate response to Bio.“

Y. Mochida and colleagues looked at 190 elderly patient [5]: „EFFICACY OF IGURATIMOD FOR RHEUMATOID ARTHRITIS IN ELDERLY PATIENTS“. Conclusion: „From the results of this study, the efficacy of IGU for elderly patients was confirmed and did not show differences with non-elderly people. IGU is an inexpensive drug with enough efficacy and thought to be possible substitute for cases with insufficient reaction with other DMARDs.“ Let's keep in mind: inexpensive drug.

And there is the study of S. Mizutani and colleagues in Clinical rheumatology [6]: „Clinical effectiveness of iguratimod based on real-world data of patients with rheumatoid arthritis“. „Disease activity scores in 177 RA patients treated using IGU were retrospectively evaluated“. The authors concluded, that iguratimod is effective for rheumatoid arthritis, especially with concomitant methotrexate. „Since all serious adverse events were in the elderly group in this study, sufficient monitoring for adverse events, especially for elderly RA patients, is needed during iguratimod therapy.“

Most if not all studies presented in this blogpost or the preceding ones would not meet the standards to apply for an approval by EMA or FDA, but iguratimod is an inexpensive csDMARD used successfully in Japan. So why isn't the drug made available in the rest of the world?

Links:

[1] Iguratimod at the EULAR Meeting 2012

http://rheumatologe.blogspot.de/2012/06/iguratimod-at-eular-2012.html

Iguratimod at the EULAR Meeting 2013

http://rheumatologe.blogspot.de/2013/06/iguratimod-at-eular-2013.html

Iguratimod at the ACR 2013 Meeting

http://rheumatologe.blogspot.de/2014/01/iguratimod-at-acr-2013-meeting-in-san.html

Iguratimod at the EULAR 2014 Meeting

http://rheumatologe.blogspot.de/2014/06/iguratimod-at-eular-2014-meeting-in.html

Iguratimod at the ACR 2015 Meeting https://rheumatologe.blogspot.com/2015/11/iguratimod-at-acr-2015-meeting-in-san.html

Iguratimod at the EULAR 2017 Meeting

https://rheumatologe.blogspot.com/2017/06/iguratimod-at-2017-eular-annual-meeting.html

[2] K. Katayama1, T. Okubo1, K. Yujiro2, R. Fukai3, T. Sato1, M. Yuichi4, S. Abe4, H. Ito4. SAT0146 INHIBITION OF RADIOGRAPHIC PROGRESSION

BY IGURATINOD IN 116 JAPANESE RHEUMATOID ARTHIRITIS PATIENTS DESPITE CONVENTIONAL SYNTHETIC DISEASE-MODIFYING ANTIRHEUMATIC DRUGS THERAPY. DOI: 10.1136/annrheumdis-2020-eular.1434

[3] D. Kobayashi1,2, E. Hasegawa2,3, Y. Wada4, S. Ito2, A. Abe2, K. Nakazono2, A. Murasawa2, I. Narita1, H. Ishikawa2. SAT0147 EFFICACY AND SAFETY OF IGURATIMOD AS FIRSTLINE DISEASE-MODIFYING ANTIRHEUMATIC DRUG THERAPY FOR PATIENTS WITH RHEUMATOID ARTHRITIS. DOI: 10.1136/annrheumdis-2020-eular.2691

[4] T. Miyamoto1,2, K. Yamazaki1. AB0350 EFFICACY OF ADDING IGURATIMOD THERAPY IN RHEUMATOID ARTHRITIS PATIENTS WHO HAD INADEQUATE RESPONSE TO BIOLOGIC DMARDS. DOI: 10.1136/annrheumdis-2020-eular.459

[5] Y. Mochida1, K. Harigane1, T. Shimazaki1, Y. Inaba2, A. Nagaoka2. AB0351 EFFICACY OF IGURATIMOD FOR RHEUMATOID

ARTHRITIS IN ELDERLY PATIENTS. DOI: 10.1136/annrheumdis-2020-eular.2639

[6] Mizutani S, Kodera H, Sato Y, Nanki T, Yoshida S, Yasuoka H. Clinical effectiveness of iguratimod based on real-world data of patients with rheumatoid arthritis [published online ahead of print, 2020 Jun 6]. Clin Rheumatol. 2020;10.1007/s10067-020-05208-y. doi:10.1007/s10067-020-05208-y https://pubmed.ncbi.nlm.nih.gov/32506311/

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Iguratimod at the 2017 EULAR Annual Meeting in Madrid

I’ve been following the development of iguratimod very closely since 2012 [1]. Iguratimod is a disease modifying anti-rheumatic drug (DMARD); chemical formula: N-(3-Formamido-4-oxo-6-phenoxy-4H-chromen-7-yl)-methanesulfonamide. “Iguratimod is characterized by inhibitory effects on immunoglobulin production in B cells as well as inhibiting cytokine production. Its' mode of action comes by suppression of nuclear factor kappa B (NF-kB) activation.” It is approved for the treatment of rheumatoid arthritis in Japan as well as in China![2]

There had been four abstracts on iguratimod at the 2017 EULAR Annual Meeting in Madrid.

K. Tokunaga and colleagues looked at [3]: “COMPARISON OF EFFICACY BETWEEN COMBINATION THERAPY WITH IGURATIMOD [IGU] AND SULFASALAZINE [SSZ] WITH METHOTREXATE IN JAPANESE PATIENTS WITH RHEUMATOID ARTHRITIS: PROPENSITY SCORE ANALYSIS”. Luckily the study excluded DMARDs like tacrolimus and bucillamine, which aren’t approved worldwide for rheumatoid arthritis. In results we read: “The remission rates of DAS28-CRP in the following year was 77.2% (44/57 patients) and 71.7% (38/53 patients; P=0.52) in the IGU and SSZ groups, respectively.” Conclusions: “Combination therapy with IGU or SSZ and methotrexate for rheumatoid arthritis did not show a significant difference in disease activity. Further studies are needed.“ According to this study iguratimod fits into the group of csDMARDs like methotrexate, leflunomide, sulfasalazine, azathioprine.

Y. Hirano and colleagues presented [4]: “LONG-TERM OUTCOME OF IGURATIMOD, CONVENTIONAL SYNTHETIC DISEASE-MODIFYNG ANTI-RHEUMATIC DRUD DEVELOPED IN JAPAN, IN JAPANESE PATIENTS WITH RHEUMATOID ARTHRITIS IN REAL-WORLD CLINICAL SETTING”. “82% of patients had factors influencing to prescribing IGU and intolerance of dose escalation of MTX was 1st reason (23.3%), old age over 80 years old was 2nd reason (16.7%) and economical reason was 3rd (14.2%)”. In conclusions the authors hinted t: “Although biological DMARDs is effective in RA patients, the cost is very expensive. IGU is comparative cheap (¥9,200/month) and suitable for RA patients with economical difficulties.” ¥9,200 is a little less than 75 €.

T. Suto and colleagues also presented long term data [5]: “EFFICACY AT THREE YEARS OF DAILY CLINICAL USE OF IGURATIMOD IN PATIENTS WITH RHEUMATOID ARTHRITIS”. “The survival rate at 3 years was 49.3%, and 8 patients discontinued the IGU therapies due to insufficient response, 12 patients due to adverse events such as exanthema, pneumonitis or hepatic disorder, and other patients based on their requests.” Conclusions: “We assessed middle-term outcome of the clinical use of iguratimod therapy in RA patients. The low DAS28-CRP and low usage rate of prednisolone at the initiation of IGU were significant factors of clinical remission achievement at 3 years.”

Iguratimod could be a useful addition to existing csDMARDs, but would have to be evaluated in randomized controlled studies. Maybe a pharmaceutical firm in Europe or the US should buy the patent for the non-Asian market and evaluate iguratimod in studies that are needed to get EMA or FDA approval. Otherwise only Japanese and Chinese patients will have access to iguratimod.

Links and References:

[1] http://rheumatologe.blogspot.de/2012/06/iguratimod-at-eular-2012.html

[2] http://rheumatologe.blogspot.de/2016/12/iguratimod-new-developments.html

[3] DOI: 10.1136/annrheumdis-2017-eular.6157

[4] DOI: 10.1136/annrheumdis-2017-eular.4852

[5] DOI: 10.1136/annrheumdis-2017-eular.6040

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What new drugs do we need in Rheumatology?

Sometimes in workshops I have been asked about unmet needs for drugs in rheumatology. At the same time my colleagues and I were looking at new drugs, emerging principles to treat rheumatoid arthritis.

If you look at current pipelines there are several drugs like sarilumab, sirukumab, brodalumab, ixekizumab and biosimilars. We already have five TNF-inhibitors, two JAK- inhibitors, an IL-6-inhibitor, an anti-CD20-agent, a second-signal-inhibitor (CD80 or CD86). Any of these drugs is expensive. Do we need more expensive drugs? Maybe – I won’t rule out that there is a niche for a new principle, but I doubt it. We hear about “promising results” of mavrilimumab (a human monoclonal antibody inhibiting human granulocyte macrophage colony-stimulating factor receptor), but is it coming to the market?

It seems that nobody is working on a drug on the price level of leflunomide. 25 mg of iguratimod (manufactured as Careram by Eisai and as Kolbet by Toyama Kagaku in Japan) [1,2] cost around 1.20-2.40 € per day, which is much less than 52.36 € per day for tofacitinib (Xeljanz) in Germany right now [3].

Iguratimod’s mode of action includes the suppression of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells). It hasn’t been tested against tofacitinib or baricitinib. But iguratimod has been tested against and in combination with methotrexate [4]. Z. Xia and colleagues have writte in “Results”: “The combination of iguratimod with MTX was superior to iguratimod or MTX monotherapy”. Too bad, they didn’t comment on MTX vs. iguratimod. The “Study of Iguratimod Plus Methotrexate Compared to Leflunomid Plus Methotrexate in Patients With Rheumatoid Arthritis” is portrait as” “The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years” [5].

Maybe iguratimod isn’t the answer to our unmet needs. But I still hope for some drug to emerge that is cheaper than any of the current monoclonal antibodies or the small molecules that have been approved by FDA or EMA.

Links:

[1] http://rheumatologe.blogspot.de/2016/12/iguratimod-new-developments.html

[2] http://rheumatologe.blogspot.de/2014/06/iguratimod-at-eular-2014-meeting-in.html

[3] http://rheumatologe.blogspot.de/2017/05/tofacitinib-xeljanz-kommt-gerade-an.html

[4] https://www.ncbi.nlm.nih.gov/pubmed/26508503

[5] https://clinicaltrials.gov/ct2/show/NCT02275299

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Iguratimod – new developments

You might have noticed, that I’ve been following the development of iguratimod very closely since 2012. Iguratimod is a disease modifying anti-rheumatic drug (DMARD); chemical formula: N-(3-Formamido-4-oxo-6-phenoxy-4H-chromen-7-yl)-methanesulfonamide. “Iguratimod is characterized by inhibitory effects on immunoglobulin production in B cells as well as inhibiting cytokine production. Its' mode of action comes by suppression of nuclear factor kappa B (NF-kB) activation.” It is approved for the treatment of rheumatoid arthritis in Japan as well as in China!

Rong Mu and colleagues presented the following study at the 2016 ACR Annual Meeting [#1622]: “Safety and Efficacy of Iguratimod in Patients with Active Rheumatoid Arthritis: A Multicenter, Single-Arm, Open-Label, Real World Study”. Conclusion: “Iguratimod was effective and well tolerated in active RA patients in this large sample phase IV clinical trial. No unexpected adverse drug reaction was found.” And let me add, I would have been surprised if this study showed any new data. But it confirms data from underpowered earlier studies. “1759 patients were enrolled in this study, among them 1751 were included in safety analysis, and 1597 patients were evaluated for efficacy.” 164 missing patients! That’s about 10%.

A second study by Lingshu Zhang and colleagues is about Sjoegren’s syndrome [#2666]: “Therapeutic Efficacy of Iguratimod in Patients with Primary Sjogren’s Syndrome”. Conclusion: “In subjects with pSS, IGU treatment resulted in clinically meaningful improvements in disease activity compared with conventional therapy. IGU affected B cell frequency and functions in pSS via inhibition of BAFF-R expression on B cells and inhibition of B cell antibody production.” The data supports the conclusion. I stumbled about the word meaningful, but as the ESSPRI is a patient reported index, I can live with the wording.

I see a potential for this drug on the world market, but I don’t see any commitment by the producers Eisai and Toyama Chemical to come to the international markets outside of East Asia.

Links:

http://rheumatologe.blogspot.de/2012/06/iguratimod-at-eular-2012.html

http://rheumatologe.blogspot.de/2015/11/iguratimod-at-acr-2015-meeting-in-san.html

Mu R. Safety and Efficacy of Iguratimod in Patients with Active Rheumatoid Arthritis: A Multicenter, Single-Arm, Open-Label, Real World Study [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). http://acrabstracts.org/abstract/safety-and-efficacy-of-iguratimod-in-patients-with-active-rheumatoid-arthritis-a-multicenter-single-arm-open-label-real-world-study/. Accessed December 21, 2016.

Zhang L, Jiang W, Chu CQ, Liu Y. Therapeutic Efficacy of Iguratimod in Patients with Primary Sjogren’s Syndrome [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). http://acrabstracts.org/abstract/therapeutic-efficacy-of-iguratimod-in-patients-with-primary-sjogrens-syndrome/. Accessed December 21, 2016.

Iguratimod at the ACR 2015 Meeting in San Francisco

There has been one publication on iguratimod at the ACR 2015 Annual Meeting in San Francisco. Iguratimod is a novel disease modifying anti-rheumatic drug (DMARD); chemical formula: N-(3-Formamido-4-oxo-6-phenoxy-4H-chromen-7-yl)-methanesulfonamide. Iguratimod is characterized by inhibitory effects on immunoglobulin production in B cells as well as inhibiting cytokine production. Its' mode of action comes by suppression of nuclear factor kappa B (NF-kB) activation. As I have already written on Iguratimod before, please look for the links below. 2012 there had been three studies, 2013 one study at the EULAR Meeting in Madrid (a study by a Chinese group), only one study at the ACR 2013 Meeting, but three studies at the EULAR 2014 meeting in Paris, also three studies at the ACR 2014 Meeting and the 2015 EULAR Meeting in Rome. But let’s look at the study now.

Tsuneo Kondo and colleagues presented: “Clinical and Radiographic Outcome of Iguratimod for Rheumatoid Arthritis”. Results: “[…] DAS28-ESR and SDAI decreased significantly from 4.49±1.33 to 3.12±1.08 and from 18.5±10.9 to 8.3±6.34 in 52 weeks respectively (P < 0.01). Remission and LDA rate in DAS28-ESR were 29.0% and 24.2%. HAQ-DI score also decreased from 1.2±0.8 to 0.85±0.79. The percentage of patients with no radiographic progression (ΔmTSS < 0.5) was 56.8%, while that of rapid radiographic progression (ΔTSS > 5) was 13.5%. The mean estimated yearly progression was 9.9 ± 15.6 at baseline. After 52 weeks of IGU treatment, the mean change was significantly reduced to 1.2 ± 2.5(P < 0.01). […]”. So, the author’s concluded: „IGU reduced disease activity and radiographic progression with RA patients. IGU is generally safe and tolerable and may have a good cost effectiveness. So iguratimod be a new useful option as small molecule DMARDs.

Iguratimod has shown to be a promising candidate for treatment of active rheumatoid arthritis and might become a needed alternative in the conventional (traditional) DMARD class. Iguratimod is approved in Japan and hopefully it will be approved in the rest of the world soon. We now have data on radiographic progression, so the drug is one step nearer to approval. But iguratimod is making progress in to little and too few steps. The sponsor of studies should more committed.

References:

Kondo T, Shibata A, Sakai R, Kikuchi J, Chino K, Okuyama A, Takei H, Amano K. Clinical and Radiographic Outcome of Iguratimod for Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/clinical-and-radiographic-outcome-of-iguratimod-for-rheumatoid-arthritis/. Accessed November 18, 2015.

Links:

Iguratimod at the EULAR Meeting 2012

http://rheumatologe.blogspot.de/2012/06/iguratimod-at-eular-2012.html

Iguratimod at the EULAR Meeting 2013

http://rheumatologe.blogspot.de/2013/06/iguratimod-at-eular-2013.html

Iguratimod at the ACR 2013 Meeting

http://rheumatologe.blogspot.de/2014/01/iguratimod-at-acr-2013-meeting-in-san.html

Iguratimod at the EULAR 2014 Meeting

http://rheumatologe.blogspot.de/2014/06/iguratimod-at-eular-2014-meeting-in.html

Iguratimod at the ACR 2014 in Boston

I have already been interested in iguratimod (IGU) for a while. I’ve blogged on IGU for the first time 2 ½ years ago after the EULAR meeting in Berlin (2012). I had been a bit disappointed in 2013, when there had been only a Chinese cell study (Iguratimod inhibits RANKL-induced osteoclastogenesis in RAW264.7 cells) at the 2013 EULAR meeting in Madrid. Earlier this year at the EULAR meeting in Paris IGU returned with three posters/studies. Please see below. Iguratimod already has been approved for the Japanese market (2012); see below. It is marketed under the brand names Careram® and KOLBET®.

Y. Kanayama and colleagues presented the following study [#1488]: “Clinical Efficacy of Add-on Iguratimod Therapy in Patients with Active Rheumatoid Arthritis Despite of Methotrexate - a Multicenter Registry.” It#s hard to tell, what this study is. I think, the authors aggregated data from existing studies and looked at 51 patients, who fulfilled the ACR/EULAR criteria for RA and didn’t respond to MTX. DAS had been reduced from 4.67 to 3.32 after 24 weeks, CDAI from 16.9 to 7.9. Remission rates were 33.3% for DAS and 27.5% for CDAI. Conclusion: “This study suggested that the new combination therapy of add-on IGU with MTX was effective in patients with active RA with inadequate response to MTX.”

Y. Hirano and colleagues presented another study [#1489]: “Influences of Disease Activity at the Initiation of Iguratimod, a Small Molecule Antirheumatic Drug, on Efficacy of Iguratimod in Patients with Rheumatoid Arthritis –a Multicenter Registry Study”. They looked at 79 patients. The study period also had been 24 weeks. In results we find: “The mean DAS28-CRP at 0, 4, 8, 12 and 24w was 4.99, 4.49, 4.29, 3.70 and 3.58 in HG [high disease activity group] and 3.24, 3.16, 2.76, 2.62 and 2.56 in MLG [moderate and low disease activity group]. DAS28-CRP was significantly decreased after 4w in HG and after 8w in MLG.” Conclusion: “This study suggests that IGU is one of the options not only in RA patients with high disease activity treated with insufficient MTX.”

T. Kondo and colleagues presented a third study [#1497]: “Efficacy and Safety of Iguratimod for Rheumatoid Arthritis.” They looked at 62 patients, who received 25 mg iguratimod during the first month and who were changed to a dosage of 50 mg afterwards. “DAS28-ESR and SDAI decreased significantly from 4.49_1.33 to 3.09_1.12 and from 18.5_10.9 to 7.44_7.11 in 24 weeks respectively (P_0.01).” “Adverse events were digestive symptom (n=6), liver dysfunction (n=3), nasal hemorrhage (n=2) and so on. There’s no severe adverse event.”  Conclusion: Iguratimod was well tolerable and may have a good cost effectiveness. So iguratimod be a new useful option as small molecule DMARDs for RA patients in a manner similar to tofacitinib.”

Sorry, as much as I want a new DMARD to treat patients with RA, who can’t receive biologics, these studies aren’t convincing and won’t be sufficient to get an approval by FDA or EMEA for iguratimod. The studies didn’t define primary endpoints, consisted of aggregated data, weren’t blinded or placebo controlled. Kondo’s conclusions are far fetched: “may have a good cost effectiveness” (cost effectiveness hadn’t been tested), “similar to tofacitinib” (hadn’t been tested against tofacitinib). And were is data on radiographic progression? As tofacitinib has been mentioned – radiographic progression was one of the critical points for not having yet optained approval by EMEA.

I’m still in favour of iguratimod, but the company has to sponsor better powered and designed studies. These studies have to include data on radiographic progression.

Links:

http://rheumatologe.blogspot.de/2012/06/iguratimod-at-eular-2012.html

http://rheumatologe.blogspot.de/2013/06/iguratimod-at-eular-2013.html

http://rheumatologe.blogspot.de/2014/06/iguratimod-at-eular-2014-meeting-in.html

http://www.eisai.com/news/news201239.html

Iguratimod at the EULAR 2014 Meeting in Paris

Iguratimod (T-614) is a novel disease modifying anti-rheumatic drug (DMARD). Iguratimod is characterized by inhibitory effects on immunoglobulin production in B cells as well as inhibiting cytokine production. Its' mode of action comes by suppression of nuclear factor kappa B (NF-kB) activation. As I have already written this before, please look for the links below. 2012 there had been three studies, 2013 one study at the EULAR Meeting in Madrid (a study by a Chinese group) and also only one study at the ACR 2013 Meeting.

This time there have been three posters/abstracts on iguratimod. But alas, all with a very limited number of patients.

[AB0464]

K. Kume and colleagues presented: "THE EFFICACY AND SAFETY OF IGURATIMOD IN RHEUMATOID ARTHRITIS PATIENTS WITH CHRONIC RENAL FAILURE". Conclusions: "Iguratimod was effective and safety in RA patients with chronic renal failure. Iguratimod could be used for RA patients with chronic renal failure." But: N=21, of whom 18 completed the study!

[AB0465]

K. Okamura and colleagues presented: "CLINICAL EFFICACY OF THE SYNTHETIC ANTI-RHEUMATIC DRUG, IGURATIMOD". Conclusions: "Our results suggest that IGU is clinically one of the useful synthetic DMARDs to RA patient." N=41 over 24 weeks. No placebo controlled study.

[AB0478]

Y. Hirano looked at: "INFLUENCES OF DISEASE ACTIVITY AT INITIATION OF IGURATIMOD, A SMALL-MOLECULE ANTIRHEUMATIC DRUG, ON EFFICACY OF IGURATIMOD IN PATIENTS WITH RHEUMATOID ARTHRITIS: A MULTICENTER STUDY". Conclusions: "More treatment options other than sufficient MTX and BIO are needed in RA patients with concomitant disease such as lung disease or renal dysfunction. High cost of BIO is another issue to inhibit improvement of signs and symptoms in RA patients. This study suggests that IGU is one of the options not only in RA patients treated with sufficient MTX but also in RA patients with high disease activity treated with insufficient MTX." N=34 over 24 weeks.

I think iguratimod has shown to be a promising candidate for treatment of active rheumatoid arthritis and might become a needed alternative in the conventional (traditional) DMARD class, but the sponsor of studies must show more commitment. Now, we don't need more of the above studies. What we need are double-blind placebo controlled studies with enough patients over a longer period of time. And we need data, if radiographic progression is inhibited or not.

Iguratimod - go for it!

Links:

Iguratimod at the EULAR Meeting 2012

http://rheumatologe.blogspot.de/2012/06/iguratimod-at-eular-2012.html

Iguratimod at the EULAR Meeting 2013

http://rheumatologe.blogspot.de/2013/06/iguratimod-at-eular-2013.html

Iguratimod at the ACR 2013 Meeting

http://rheumatologe.blogspot.de/2014/01/iguratimod-at-acr-2013-meeting-in-san.html

Iguratimod at the ACR 2013 Meeting in San Diego

Iguratimod (T-614) is a novel disease modifying anti-rheumatic drug (DMARD). Iguratimod is characterized by inhibitory effects on immunoglobulin production in B cells as well as inhibiting cytokine production. Its' mode of action comes by suppression of nuclear factor kappa B (NF-kB) activation. As I have already written this before, please look for the links below. 2012 there had been three studies, 2013 one study at the EULAR Meeting in Madrid (a study by a Chinese group).

There has only been on study at the ACR 2013 Meeting. Daisuke Kobayashi and colleagues published the following study [#1422]: “Efficacy and Safety Of a Novel Disease-Modifying Antirheumatic Drug, Iguratimod, As Add-On Therapy For Patients With Rheumatoid Arthritis.” The study has been small (N=26). Conclusion: “Iguratimod is effective as add-on therapy in RA patients who have shown inadequate responses to previous therapy, although caution is necessary regarding hemorrhagic tendency in patients receiving warfarin, which was cautioned by Ministry of Health, Labour and Welfare of Japan.”

I think iguratimod is indeed a promising candidate for treatment of active rheumatoid arthritis and might become a needed alternative in the conventional (traditional) DMARD class. I wished the sponsor would press more for results, also for studies, which would result in an appearance on the world market.

Link:

Iguratimod at the EULAR Meeting 2012 http://rheumatologe.blogspot.de/2012/06/iguratimod-at-eular-2012.html

Iguratimod at the EULAR Meeting 2013 http://rheumatologe.blogspot.de/2013/06/iguratimod-at-eular-2013.html